Shorter Median Survival Time Research Articles

Comparing survival and outcomes in isolated versus polytrauma-associated TBI: a retrospective cohort study.

One in four patients with moderate to severe traumatic brain injury (TBI) also has other body district injuries (OBD). The impact of OBD on mortality and disability is debated. This study compared outcomes of TBI patients with polytrauma (p-TBI) versus isolated TBI (alone-TBI) and identified outcome determinants, focusing on survival time and prognosis. This single-center, retrospective cohort study analyzed 193 patients with moderate to severe TBI admitted to an ICU from 2011 to 2012. Patients were divided into p-TBI and alone-TBI groups. Clinical, demographic, and outcome data were extracted from medical records. Key outcomes included survival time and Glasgow Outcome Scale-Extended (GOSE) scores at 1-year. The alone-TBI group (N.=126) was older with more comorbidities and higher use of antiplatelet/anticoagulant medications. The p-TBI group (N.=67) had greater physiological dysfunction (hypotension, acidosis, anemia, coagulopathy). Trauma severity (Glasgow Coma Scale), in-hospital mortality, and GOSE were similar between groups, but p-TBI patients had a shorter median survival time (3.5 vs. 18 days, P=0.016). Key determinants of poor outcomes were age, coagulopathy, neurological impairment at admission, and intracranial hypertension. Polytrauma does not appear to be independently associated with the prognosis of moderate to severe TBI patients but is associated with earlier mortality. Coagulopathy and physiological instability are more critical factors in determining mortality and poor outcomes. Future research should explore whether polytrauma is a bystander in TBI or if it has a causal role in adverse outcomes.

Abstract 4138622: Cardiac Rhabdomyosarcoma: An Updated Review of the English Literature From 1980 Through 2023

Cardiac Rhabdomyosarcoma (CR) is a rare malignant neoplasm of the heart occurring in all age groups and genders. It can arise anywhere in the heart with varied clinical presentation. Available data on CR are mainly from case reports and series that are limited by small sizes. The purpose of this study was to characterize the epidemiology, presentation, management, hospital course, and outcomes of CR published in the English literature from 1980-2023. Methods: We reviewed and included all published case reports with a diagnosis of CR in adult patients (age >18 years) on PubMed and Google Scholar using the keywords “primary cardiac tumor” and “cardiac rhabdomyosarcoma”. Data was extracted onto an Excel spreadsheet for analysis and the outcomes of interest were demographics, clinical presentation, diagnostic modalities, management, complications, and outcomes. We used descriptive statistics to analyze the data. Results: Among a total of 97 patients from 19 countries included in this study, 54% were males and the median age was 49 years (range 18-80). The main symptoms were dyspnea (37.1%), palpitations (23.7%), chest pains (16.5%) and syncope (6.5%). Hypotension or heart failure and arrhythmias were present in 10.3% and 9.3%, respectively and 5.2% had pericardial effusion. In addition to those with metastatic tumors, 22.7% had chronic co-morbidities. The majority of the cases were primary tumors (85.6%), and the remainder were (14.4%). All patients had at least one imaging modality including echocardiography (89%) and CT/MRI (84%). The commonest sites of cardiac involvement were the left atrium (35%), right atrium (33%), right ventricle (20%), and left ventricle (12%). Approximately 68% involved a single cardiac site while 32% involved multiple sites. Among the patients, 96% underwent surgery while 33% and 25% had chemotherapy and 25% radiotherapy, respectively. The median length of hospital stay was 11 days (range, 2-68 days), and mortality was recorded in 79.3% (77/97) of the patients. The median survival time was reported in 42 patients, and it was 6 months (range, 0-36 months). Conclusion: Cardiac rhabdomyosarcoma is a rare and aggressive malignant neoplasm. Most cases are primary tumors with poor outcomes such as a very short median survival time and a very high mortality rate despite the combination of surgery, chemotherapy, and radiotherapy. This calls for further research into the early diagnosis and optimal management strategies to improve outcomes.

Survival status and prognostic factors analysis in patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension

Objective: To analyze the survival status and prognostic factors of patients with hereditary hemorrhagic telangiectasia-associated pulmonary arterial hypertension (HHT-PAH). Methods: This prospective study included patients diagnosed with HHT-PAH at the Fuwai Hospital of the Chinese Academy of Medical Sciences and Guangdong General Hospital from August 2009 to December 2019. Patients were followed up every 6 months±2 weeks, with all-cause mortality as the study endpoint. Multivariate Cox proportional hazards regression mode was used to further screen and validate the prognostic factors. Survival curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare the survival time differences between patients with and without hepatic arteriovenous malformations. Results: A total of 18 HHT-PAH patients were included, with 14 females (77.8%) and a median age [M (Q1, Q3)] of 39 (32, 45) years. The median follow-up time was 129 (51, 156) months. During the follow-up period, 12 patients (66.7%) died, with a median survival time of 70 (32, 123) months. The 1-year, 3-year, 5-year, and 10-year survival rates were 100.0%, 70.8%(95%CI: 52.3%-96.0%), 53.1%(95%CI: 34.0%-83.0%), and 26.6%(95%CI: 10.6%-66.4%), respectively. HHT-PAH patients with hepatic arteriovenous malformations had a shorter median survival time than those without hepatic arteriovenous malformations [31.0 months (95%CI: 16.6-45.4 months) vs 84.0 months (95%CI: 54.4-113.6 months), P=0.024]. Cox proportional hazards regression analysis showed that hepatic arteriovenous malformation (HR=4.493, 95%CI: 1.064-18.978) was a risk factor for all-cause mortality in HHT-PAH patients. Conclusions: The 10-year survival rate of HHT-PAH patients is poor. The presence of hepatic arteriovenous malformations is a risk factor for mortality in HHT-PAH patients.

Engineered protein destabilization reverses intrinsic immune evasion for candidate vaccine pan-strain KSHV and SARS-CoV-2 antigens.

Both Kaposi sarcoma herpesvirus LANA and SARS coronavirus 2 RdRp/nsp12 are highly conserved replication proteins that evade immune processing. By deleting the LANA central repeat 1 domain (LANA ΔCR1 ) or by dividing RdRp into two separated fragments (RdRp Frag ) to maximize nascent protein mis-folding, cis peptide presentation was increased. Native LANA or RdRp SIINFEKL fusion proteins expressed in MC38 cancer cells were not recognized by activated OT-1 CD8 + cells against SIINFEKL but cytotoxic recognition was restored by expression of the corresponding modified proteins. Immunocompetent syngeneic mice injected with LANA- or RdRp-SIINFEKL MC38 cells developed rapidly-growing tumors with short median survival times. Mice injected with LANA ΔCR1 - or RdRp Frag -SIINFEKL had partial tumor regression, slower tumor growth, longer median survival, as well as increased effector-specific tumor-infiltrating lymphocytes. These mice developed robust T cell responses lasting at least 90 days post-injection that recognized native viral protein epitopes. Engineered vaccine candidate antigens can unmask virus-specific CTL responses that are typically suppressed during native viral infection.

The role of vector-borne pathogens and cardiac Striatin genotype on survival in boxer dogs with arrhythmogenic right ventricular cardiomyopathy

Introduction/ObjectivesRisk factors for severe disease in boxer dogs with arrhythmogenic right ventricular cardiomyopathy (ARVC) are not well understood. This study's objective was to determine whether Striatin genotype or canine vector-borne pathogen (CVBP) exposure/infection in boxer dogs with ARVC was associated with disease severity or survival. AnimalsSixty-four client-owned, adult boxer dogs with ARVC were included in the study. Materials and MethodsThis was a prospective descriptive study. Disease severity was determined by echocardiography and Holter monitoring. Potential risk factors included CVBP exposure/infection (Anaplasma spp., Babesia spp., Bartonella spp., Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia spp., and Rickettsia spp.) and Striatin genotype. ResultsThe median survival time after enrollment was 270 days (95% confidence interval [CI]: 226–798 days), and the median age at the time of death or censoring was 11 years (95% CI: 10.3–11.7 years). Striatin mutation genotype results included 31 homozygous-negative, 26 heterozygous-positive, and seven homozygous-positive boxer dogs. Ten boxer dogs had exposure to Bartonella spp., four to Rickettsia, two to Ehrlichia spp., and one to Anaplasma spp. Striatin homozygous–positive boxer dogs had a shorter median survival time (93 days vs. 373 days for heterozygous [P=0.010] and 214 days for homozygous negative [P=0.036]). Exposure/infection to CVBP was not associated with median survival time or age at the time of death. DiscussionStriatin homozygous positive boxer dogs with ARVC had shorter survival times and were younger at the time of death. Exposure or infection with CVBP did not appear to influence survival time. Study LimitationsSelection bias for more severe disease limited the ability to assess the relationship between CVBP infection/exposure and disease severity, and overall small sample size limited statistical power. Extracardiac disease and treatment protocols were not controlled. ConclusionsStriatin genotype screening can be considered for prognostic information. Exposure/infection to CVBP appears unlikely to influence survival time for boxer dogs with ARVC.

Analysis of pancreatic cancer treatment and survival disparities in Florida throughout the Covid-19 pandemic

IntroductionPancreatic ductal adenocarcinoma (PDAC) is currently the third-leading cause of cancer-related death in the United States. African Americans (AAs) with PDAC have worse survival in comparison to other racial groups. The COVID-19 pandemic caused significant stress to the healthcare system. We aim to evaluate the pandemic's impact on already known disparities in newly diagnosed patients with PDAC in Florida. MethodsThis is a retrospective analysis of newly diagnosed patients with PDAC in the OneFlorida+ Data Trust based upon date of diagnosis: Pre-pandemic (01/01/2017- 09/30/2019), Transition (10/01/2019-02/28/2020), and Pandemic (03/1/2020-10/31/2020). Primary endpoints are time to treatment initiation and rate of surgery and secondary endpoint is survival time. Disparities due to age, sex, race, and income were also evaluated. Chi-squared or Fisher's exact test when necessary, Kruskal-Wallis test, and Kaplan-Meier analysis with log-rank test were performed to compare the differences between the comparative groups for categorical, quantitative, and survival outcomes, respectively. Multivariable regression analyses were conducted to estimate the effects of cofactors. Results934 patients with a median age of 67 years were included. There were 47.8% females and 52.2% males; 19.4% AA, 70.2% Caucasian, 10.4% Other race; median income was $53,551. While we observed a significant reduction in the diagnosis rate of new PDAC cases during the pandemic, there were no significant differences in demographic distributions among the three cohorts. Time to treatment did not significantly change from the pre-pandemic to the pandemic, and no difference was observed across all demographics. Rate of surgery increased significantly from the pre-pandemic (35.8%) to the pandemic (55.6%). AAs in the pre-pandemic cohort had a significantly lower rate of surgery of 25.0% compared to 41.7% in Caucasians. AAs, patients ≥ 67 years, and income < $53,000 had significantly higher hazards to death and shorter median survival time (mST). ConclusionsWhile no differences in time to initial treatment are observed among the newly diagnosed PDAC patients, there remain significant disparities in the rate of surgery and overall survival. Observing a significant reduction in diagnosis rate and analyzing disparities can provide insight into the effect of a resource-restricting pandemic for patients with newly diagnosed PDAC.

Evaluation of clinical profiles, surgical experience and outcomes of ileosigmoid knotting in low-resource setup: A retrospective cohort study at Jimma University Medical Center.

Bowel obstruction is a mechanical or functional blockade of intestinal contents from evacuation to the adjacent distal bowel or external environment. It poses significant morbidity and mortality in both high-income and low-to-middle-income countries. Ileosigmoid knotting is a special form of obstruction where the small bowel often ileum wraps around the sigmoid colon or vice versa. It is the severest form of bowel obstruction, involving both the small and large bowels in a compound manner. It is common where sigmoid volvulus is common and geographic areas with a bulky diet. An institution-based retrospective cohort study was employed among purposively selected 40 surgical patients with ileosigmoid knotting records from July 2020 to July 2023 at Jimma University Medical Center. To estimate and compare the survival probabilities, the Kaplan-Meir method and log-rank test were used. A Cox-regression analysis was fitted to identify independent predictors of time to death. Among a cohort of 40 patients followed for 347 person-days at Jimma University Medical Center, 11 (27.5%) had died. The overall incidence rate of death was 3.2 (95% CI 1.8, 5.7) per 100 person-days. In multivariable Cox-regression analysis, age (AHR=1.15; 95% CI: 1.04-1.28), shock at presentation (AHR=30.50: 95% CI 1.25-742.54), comorbidities (AHR=5.81; 95% CI 1.19-28.23), pulse rate intraoperatively (AHR=1.19; 95% CI: 1.01-1.40), postoperative pulse rate (AHR=1.07; 95% CI: 1.01-1.14) were independently associated with time to death. The incidence of death among surgical patients with ileosigmoid knotting was high and also had a shorter median survival time. Age, shock at presentation, comorbidities, pulse rate intraoperatively, and postoperative pulse rate were found to be statistically significant predictors of time to death and outcome among surgical patients with Ileosigmoid knotting.

Long noncoding RNA LINC00921 serves as a predictive biomarker for lung adenocarcinoma: An observational study.

Lung adenocarcinoma (LUAD) is usually diagnosed at advanced stages. Hence, there is an urgent need to seek an effective biomarker to predict LUAD status. Long noncoding RNAs (lncRNAs) play key roles in the development of tumors. However, the relationship between LINC00921 and LUAD remains unclear. The gene expression data of LUAD were downloaded from the Cancer Genome Atlas database to investigate the expression level of LINC00921 in LUAD. Diagnostic ability analysis, survival analysis, tumor mutational burden analysis, and immune cell infiltration analysis of LINC00921 in LUAD patients were performed simultaneously. According to the median expression value of LINC00921, patients were divided into LINC00921 high- and low-expression groups. The function of LINC00921 in LUAD was identified through difference analysis and enrichment analysis. Moreover, drugs that may be relevant to LUAD treatment were screened. Finally, blood samples were collected for real-time polymerase chain reaction. LINC00921 was significantly lower in LUAD tumor tissues. Notably, patients with low expression of LINC00921 had a shorter median survival time. Decreased immune cell infiltration in the tumor microenvironment in the low LINC00921 expression group may contribute to poorer patient outcomes. Tumor mutational burden was significantly different in survival between the LINC00921 high- and low-expression groups. In addition, LINC00921 may exert an influence on cancer development through its regulation of target genes transcription. Glyceraldehyde-3-phosphate dehydrogenase-related drugs may be more likely to be therapeutically effective in LUAD. LINC00921 was able to be used as the potential diagnostic indicator for LUAD.

New tricks for old drugs- praziquantel ameliorates bleomycin-induced pulmonary fibrosis in mice

BackgroundPulmonary fibrosis is a chronic progressive disease with complex pathogenesis, short median survival time, and high mortality. There are few effective drugs approved for pulmonary fibrosis treatment. This study aimed to evaluate the effect of praziquantel (PZQ) on bleomycin (BLM)-induced pulmonary fibrosis.MethodsIn this study, we investigated the role and mechanisms of PZQ in pulmonary fibrosis in a murine model induced by BLM. Parameters investigated included survival rate, lung histopathology, pulmonary collagen deposition, mRNA expression of key genes involved in pulmonary fibrosis pathogenesis, the activity of fibroblast, and M2/M1 macrophage ratio.ResultsWe found that PZQ improved the survival rate of mice and reduced the body weight loss induced by BLM. Histological examination showed that PZQ significantly inhibited the infiltration of inflammatory cells, collagen deposition, and hydroxyproline content in BLM-induced mice. Besides, PZQ reduced the expression of TGF-β and MMP-12 in vivo and inhibited the proliferation of fibroblast induced by TGF-β in vitro. Furthermore, PZQ affected the balance of M2/M1 macrophages.ConclusionsOur study demonstrated that PZQ could ameliorate BLM-induced pulmonary fibrosis in mice by affecting the balance of M2/M1 macrophages and suppressing the expression of TGF-β and MMP-12. These findings suggest that PZQ may act as an effective anti-fibrotic agent for preventing the progression of pulmonary fibrosis.

Beyond boundaries: unraveling innovative approaches to combat bone-metastatic cancers.

Evidence demonstrated that bones, liver, and lungs are the most common metastasis sites in some human malignancies, especially in prostate and breast cancers. Bone is the third most frequent target for spreading tumor cells among these organs and tissues. Patients with bone-metastatic cancers face a grim prognosis characterized by short median survival time. Current treatments have proven insufficient, as they can only inhibit metastasis or tumor progression within the bone tissues rather than providing a curative solution. Gaining a more profound comprehension of the interplay between tumor cells and the bone microenvironment (BME) is of utmost importance in tackling this issue. This knowledge will pave the way for developing innovative diagnostic and therapeutic approaches. This review summarizes the mechanisms underlying bone metastasis and discusses the clinical aspects of this pathologic condition. Additionally, it highlights emerging therapeutic interventions aimed at enhancing the quality of life for patients affected by bone-metastatic cancers. By synthesizing current research, this review seeks to shed light on the complexities of bone metastasis and offer insights for future advancements in patient care.

Occupational and Environmental Asbestos Exposure and Survival of Patients with Asbestos-Related Cancer: A Follow-Up Study on Patients with Malignant Mesothelioma and Asbestos-Related Lung Cancer in Korea.

Malignant mesothelioma and asbestos-related lung cancer are typically associated with a poor prognosis. However, it has been observed that some patients with these cancers survive significantly longer than the average survival period. While many preliminary studies have investigated factors influencing patient survival, the specific impact of asbestos exposure has not been thoroughly explored. We followed up with 546 patients with malignant mesothelioma and 902 patients with asbestos-related lung cancer, all identified as asbestos victims between 2009 and 2021. In both malignant mesothelioma and asbestos-related lung cancer, patients with occupational asbestos exposure exhibited not only shorter median survival times but also lower 3- and 5-year survival rates compared to those with environmental exposure. Additionally, a longer duration of occupational exposure and closer proximity to the source of asbestos were linked to shorter survival times and lower survival rates. Among the patients with occupational asbestos exposure, the highest hazard ratios (HRs) were observed in those who worked in the production of asbestos-containing products across both cancer types. In contrast, significant HRs were only noted in mesothelioma patients who lived near asbestos industries, slate houses, and redevelopment areas, within the environmentally exposed group.

Associations between neuropsychiatric symptoms, pathology in neuropathological cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies

AbstractBackgroundNeuropsychiatric symptoms (NPS) are frequent in Alzheimer’s Disease dementia (ADD) but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co‐occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). Previous studies have shown that both ADLB and DLB cases have faster cognitive and/or functional decline compared to AD. However, the differences in NPS severity over disease course and survival in these pathologic subgroups is not well understood.MethodCases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a final neuropathologic diagnosis of DLB (±AD co‐pathology; n = 65), ADLB (n = 89), AD (without LB) (n = 140), and controls (no neuropathological diagnosis) (n = 82) were included. Total NPI‐Q (scores ranging from 0‐36) at time of enrollment and within 2.5 years of death were calculated for all groups. Statistical analysis utilizing ANCOVA (adjusting for age, sex, baseline MMSE and cognitive symptom duration) with pairwise comparisons, and Kaplan‐Meier curves were completed.ResultAge at onset of cognitive symptoms was not different between pathology groups. NPI‐Q scores at enrollment were highest in ADLB (7.33 ± 4.85), and higher (p&lt;0.001) than DLB (5.10 ± 3.37), AD (4.54 ± 3.63) and controls (1.78 ± 1.70). At final evaluation, NPI‐Q scores were highest in DLB (10.04 ± 6.28), followed by ADLB (8.0 ± 4.), and ADD (7.61 ± 5.05) when compared to controls (2.78 ± 3.97) (all p&lt;0.001). DLB and AD demonstrated significant increases in NPI‐Q severity during follow up (p &lt; 0.001). AD had longer survival time (5.8 years) compared to ADLB (4.0 years) and DLB (3.9 years). Subjects with NPS had a shorter median survival time (3.4 years) compared to subjects without NPS (6.5 years; p = 0.002).ConclusionA higher NPS burden and shorter survival is seen in both DLB and ADLB, as compared with AD. This suggests that diffuse neocortical LB pathology is not the major driver of either NPS or survival.

Correlation between malignant peritoneal cytology and survival in patients with uterine leiomyosarcoma and endometrial stromal sarcoma

ObjectiveThis study aimed to examine the correlation between malignant peritoneal cytology and overall survival among patients with uterine leiomyosarcoma and endometrial stromal sarcoma.MethodsPatients with uterine leiomyosarcoma and endometrial stromal sarcoma...

Effect of metastatic calcification on complication rate and survival in 74 renal transplant cats (1998-2020).

To report the incidence of metastatic calcification in cats with renal failure presenting for renal transplantation, and to determine if metastatic calcification detected prior to renal transplantation is associated with complication rates and patient survival. Retrospective case series. Seventy-four cats. In imaging studies, 178 feline renal transplant recipients from 1998 to 2020 were evaluated for metastatic calcification. Demographic, clinicopathological data, intraoperative complications, postoperative complications, need for hemodialysis, and survival times were recorded. Exclusion criteria were cats lacking imaging reports and cats with gastric, renal, or tracheal/bronchial calcification alone. Univariable and multivariable analyses were performed to determine variables that were independently associated with survival. Kaplan-Meier analysis was used to generate survival plots and estimate median survival times with a 95% confidence interval (CI). Seventy four of 178 cats met the inclusion criteria. Fifteen of 74 (20.3%) cats had metastatic calcification prior to renal transplantation. Twelve of 74 (16.2%) cats developed calcification following transplantation, and 47 of 74 (63.5%) cats had no calcification during the study period. Median follow-up time was 472 days, with a range of 0-1825 days. Cats with pretransplant calcification had shorter median survival times (147 days) than cats without calcification (646 days) (p = .0013). Metastatic calcification pretransplant was associated with an increased risk of death by 240% (95% CI, 1.22-4.71). Metastatic calcification in renal transplant cats is a negative prognostic indicator and is associated with decreased survival times. These findings may help guide therapeutic recommendations and owner expectations in cats undergoing renal transplantation.

Breast cancer brain metastases: The graded prognostic assessment index (GPA) in a real-world low- and middle-income (LMIC) population.

e18531 Background: Up to 15% of breast cancer patients develop brain metastases during the course of their disease. Graded Prognostic Assessment (GPA) estimates survival for patients with brain metastases. This retrospective analysis assesses the applicability of the GPA and highlights the outcomes for patients from a Low- and Middle-income Country (LMIC). We compared the GPA-predicted survival for each patient with the actual overall survival. Methods: A single-center retrospective analysis of patients identified from the neurosurgery, radiation therapy and palliative care databases of the Instituto Nacional de Câncer (INCA), Brazil, from October 2018 to June 2020. Survival analyzes were performed using the Kaplan-Meier method and the curves were compared by the Log-rank test. Results: We identified 110 patients with breast cancer brain metastasis and 84 patients were followed through December 2021. 10 patients were still alive at the end of follow-up. Median age at breast cancer diagnosis was 48 years, and median time from breast cancer diagnosis to brain metastases diagnosis was 30.6 months. 62% were premenopausal and ECOG-PS was 0 - 1 in 44%, and 2 in 25% of patients. 94% of tumors were of ductal histology, 43% hormone receptor (HR) +/HER2 - disease, 30% triple-negative, and 27% HER2 + (17% HR+ and 10% HR-). 22% stage IV disease at diagnosis. The median time from breast cancer diagnosis to brain metastases was 30.6 months (range, 0.3 to 232 months). 95% of patients were symptomatic at the time of the brain imaging, mainly headache and focal neurological deficit. 64% of patients had less than three brain metastases. Patients underwent neurosurgery (71%), stereotactic radiosurgery (13%) and WBRT (38%), and the median time from brain metastases diagnosis to local treatment was 18, 20 and 10 days, respectively. Median time from brain metastases to death was 5.5 months, being 4.0 months for HR+HER2-, 4.5 months for triple-negative, and 12.0 months for HER2+ disease (p = 0.18). The median time calculated according to the GPA for the whole patient population was 13 months. Conclusions: Breast cancer patients with brain metastases had a shorter median survival time than the one estimated by the GPA. We hypothesize that a delay between CNS symptoms and brain imaging may explain this worse outcome. The prognostic score is an important tool to assist in choosing therapeutic options. It can also highlight health disparities and consequently stimulate the search for potential strategies to improve patients outcomes.

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Inequalities in survival and care across social determinants of health in a cohort of advanced lung cancer patients in Quebec (Canada): A high-resolution population-level analysis.

Advanced lung cancer patients exposed to breakthrough therapies like EGFR tyrosine kinase inhibitors (EGFR-TKI) may experience social inequalities in survival, partly from differences in care. This study examined survival by neighborhood-level socioeconomic and sociodemographic status, and geographical location of advanced lung cancer patients who received gefitinib, an EGFR-TKI, as first-line palliative treatment. Differences in the use and delay of EGFR-TKI treatment were also examined. Lung cancer patients receiving gefitinib from 2001 to 2019 were identified from Quebec's health administrative databases. Accounting for age and sex, estimates were obtained for the median survival time from treatment to death, the probability of receiving osimertinib as a second EGFR-TKI, and the median time from biopsy to receiving first-line gefitinib. Among 457 patients who received first-line treatment with gefitinib, those living in the most materially deprived areas had the shortest median survival time (ratio, high vs. low deprivation: 0.69; 95% CI: 0.47-1.04). The probability of receiving osimertinib as a second EGFR-TKI was highest for patients from immigrant-dense areas (ratio, high vs. lowdensity: 1.95; 95% CI: 1.26-3.36) or from Montreal (ratio, other urban areas vs. Montreal: 0.39; 95% CI: 0.16-0.71). The median wait time for gefitinib was 1.27 times longer in regions with health centers peripheral to large centers in Quebec or Montreal in comparison to regions with university-affiliated centers (95% CI: 1.09-1.54; n = 353). This study shows that real-world variations in survival and treatment exist among advanced lung cancer patients in the era of breakthrough therapies and that future research on inequalities should also focus on this population.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies

To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies. The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated. A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027). The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Myo1e overexpression in lung adenocarcinoma is associated with increased risk of mortality

This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer’s pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

Identification of immune biomarkers associated with basement membranes in idiopathic pulmonary fibrosis and their pan-cancer analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease of unknown etiology, characterized by diffuse alveolitis and alveolar structural damage. Due to the short median survival time and poor prognosis of IPF, it is particularly urgent to find new IPF biomarkers. Previous studies have shown that basement membranes (BMs) are associated with the development of IPF and tumor metastasis. However, there is still a lack of research on BMs-related genes in IPF. Therefore, we investigated the expression level of BMs genes in IPF and control groups, and explored their potential as biomarkers for IPF diagnosis. In this study, the GSE32537 and GSE53845 datasets were used as training sets, while the GSE24206, GSE10667 and GSE101286 datasets were used as validation sets. In the training set, seven immune biomarkers related to BMs were selected by differential expression analysis, machine learning algorithm (LASSO, SVM-RFE, Randomforest) and ssGSEA analysis. Further ROC analysis confirmed that seven BMs-related genes played an important role in IPF. Finally, four immune-related Hub genes (COL14A1, COL17A1, ITGA10, MMP7) were screened out. Then we created a logistic regression model of immune-related hub genes (IHGs) and used a nomogram to predict IPF risk. The nomogram model was evaluated to have good reliability and validity, and ROC analysis showed that the AUC value of IHGs was 0.941 in the training set and 0.917 in the validation set. Pan-cancer analysis showed that IHGs were associated with prognosis, immune cell infiltration, TME, and drug sensitivity in 33 cancers, suggesting that IHGs may be potential targets for intervention in human diseases including IPF and cancer.