Disease Rating Research Articles

Availability and accessibility of indigenous foods in Gauteng region, South Africa

While South Africa maintains national food security, food insecurity persists at the household level, with not all households having access to sufficient food. Proposals to address this include promoting the consumption of indigenous foods (IF). However, urbanization in the Gauteng region has sparked a nutrition transition, characterized by increased consumption of Western diets, resulting in rising rates of malnutrition and non-communicable diseases. This study sought to assess the availability and accessibility of indigenous foods in the region for residents. A quantitative cross-sectional research survey was conducted in the Gauteng region, involving 746 participants who provided insights into their ways of acquiring indigenous foods and rated their overall availability. Additionally, the survey gathered opinions on IF availability across different settings and collected suggestions for improving IF accessibility. Among a list of 18 South African indigenous foods, between 55.2 and 77.2% of participants did not know where they could be obtained. Acquisition through vendors, with a maximum of 14% of respondents, emerged as relatively more popular compared to food markets, spaza shops, supermarkets, and home gardens. The majority of surveyed participants (55%) perceived indigenous foods as unavailable in the region. Agreement rates for the availability of indigenous foods for sale or serving in various settings were 53.5% for supermarkets, 42% for schools, 44.2% for hospitals, and 37.5% for workplaces. Respondents suggested several strategies to enhance IF accessibility in the region, including marketing, home gardens, farms, supermarkets, education, elders, restaurants, and schools/universities. Overall, there is a need for increased education on the nutritional benefits of indigenous foods and the implementation of policies to improve their accessibility in urbanized provinces like Gauteng.

A disease-associated gene desert directs macrophage inflammation through ETS2

Increasing rates of autoimmune and inflammatory disease present a burgeoning threat to human health1. This is compounded by the limited efficacy of available treatments1 and high failure rates during drug development2, highlighting an urgent need to better understand disease mechanisms. Here we show how functional genomics could address this challenge. By investigating an intergenic haplotype on chr21q22—which has been independently linked to inflammatory bowel disease, ankylosing spondylitis, primary sclerosing cholangitis and Takayasu’s arteritis3–6—we identify that the causal gene, ETS2, is a central regulator of human inflammatory macrophages and delineate the shared disease mechanism that amplifies ETS2 expression. Genes regulated by ETS2 were prominently expressed in diseased tissues and more enriched for inflammatory bowel disease GWAS hits than most previously described pathways. Overexpressing ETS2 in resting macrophages reproduced the inflammatory state observed in chr21q22-associated diseases, with upregulation of multiple drug targets, including TNF and IL-23. Using a database of cellular signatures7, we identified drugs that might modulate this pathway and validated the potent anti-inflammatory activity of one class of small molecules in vitro and ex vivo. Together, this illustrates the power of functional genomics, applied directly in primary human cells, to identify immune-mediated disease mechanisms and potential therapeutic opportunities.

Decadal Analysis of Age-Adjusted Mortality Rates for Acute and Chronic Kidney Disease in Brazil, 2000-2021.

Introduction Renal failure, comprising acute kidney injury (AKI) and chronic kidney disease (CKD), involves a decline or loss of kidney function. AKI is sudden and reversible, with a rapid decline in function over hours to days, while CKD involves persistent abnormalities lasting at least three months. Developing countries are seeing a rise in AKI cases, especially in critically ill patients. Globally, there's a growing occurrence and mortality rate linked to CKD. Methods The study used a retrospective cross-sectional design to analyze AKIand CKDmortality rates in Brazil from 2019 to 2022. Data on population and demographics, including sex and age, were obtained from the Brazilian Institute of Geography and Statistics. Mortality data for kidney diseases were sourced from the Brazilian Hospital Information System. The analysis utilized the Joinpoint Regression Programto calculate average annual percentage changes (AAPCs) and their respective 95% confidence intervals. Weighted Bayesian information criterion was used to determine the significance levels and identify the best-fitting combination of line segments and joinpoints. Results The study findings revealed a significant rise in AKI mortality rates for both males and females, from 2008 to 2021 (APC = 3.16;CI: 2.29 to 5.93), with higher mortality rates recorded among males compared to women over the entire study period. Analyses according to age groups showed that males between the ages 40 to 49 experienced the most rapid increase in mortality during the 2019 - 2021 period (APC = 35.41; CI: 16.72 to 46.57); meanwhile, the most rapid increase in mortality for females was observed from 2019 to 2021, and this was among those aged 30 to 39 (APC = 40.33; CI = 6.48 to 59.78). Furthermore, there was an observable upward trend in mortality related to CKD(APC = 0.70; CI: 0.41 to 1.01), with males consistently having higher mortality rates throughout the entire study period. The elderly population, both males and females, experienced the most rapid increase in CKD-related mortality, with AAPCvalues of 2.32 (CI: 1.82 to 2.89) for males and 1.62 (CI: 1.08 to 2.10) for females. Conclusion We observed a consistent increase in mortality rates from acute kidney diseases for both males and females since 2008, with males experiencing higher mortality rates overall. The study highlighted the need for further researchto understand the underlying factors contributing to these trends. Additionally, interventions targeting modifiable risk factors and improving access to healthcare could help reduce mortality related to renal failure.

Disease progression in proposed brain-first and body-first Parkinson’s disease subtypes

A new Parkinson’s disease (PD) subtyping model has been recently proposed based on the initial location of α-synuclein inclusions, which divides PD patients into the brain-first subtype and the body-first subtype. Premotor RBD has proven to be a predictive marker of the body-first subtype. We found compared to PD patients without possible RBD (PDpRBD–, representing the brain-first subtype), PD patients with possible premotor RBD (PDpRBD+, representing the body-first subtype) had lower Movement Disorders Society Unified Parkinson’s Disease Rating Scale part III (MDS UPDRS-III) score (p = 0.022) at baseline but presented a faster progression rate (p = 0.009) in MDS UPDRS-III score longitudinally. The above finding indicates the body-first subtype exhibited a faster disease progression in motor impairments compared to the brain-first subtype and further validates the proposed subtyping model.

A Random Forest Algorithm for Assessing Risk Factors Associated With Chronic Kidney Disease: Observational Study.

The prevalence and mortality rate of chronic kidney disease (CKD) are increasing year by year, and it has become a global public health issue. The economic burden caused by CKD is increasing at a rate of 1% per year. CKD is highly prevalent and its treatment cost is high but unfortunately remains unknown. Therefore, early detection and intervention are vital means to mitigate the treatment burden on patients and decrease disease progression. In this study, we investigated the advantages of using the random forest (RF) algorithm for assessing risk factors associated with CKD. We included 40,686 people with complete screening records who underwent screening between January 1, 2015, and December 22, 2020, in Jing'an District, Shanghai, China. We grouped the participants into those with and those without CKD by staging based on the glomerular filtration rate staging and grouping based on albuminuria. Using a logistic regression model, we determined the relationship between CKD and risk factors. The RF machine learning algorithm was used to score the predictive variables and rank them based on their importance to construct a prediction model. The logistic regression model revealed that gender, older age, obesity, abnormal index estimated glomerular filtration rate, retirement status, and participation in urban employee medical insurance were significantly associated with the risk of CKD. On RF algorithm-based screening, the top 4 factors influencing CKD were age, albuminuria, working status, and urinary albumin-creatinine ratio. The RF model predicted an area under the receiver operating characteristic curve of 93.15%. Our findings reveal that the RF algorithm has significant predictive value for assessing risk factors associated with CKD and allows the screening of individuals with risk factors. This has crucial implications for early intervention and prevention of CKD.

Identifying risk factors and mortality rate of premature coronary artery disease in young Saudi population

Coronary artery disease is a leading cause of morbidity and mortality worldwide. It occurs due to a combination of genetics, lifestyle, and environmental factors. Premature coronary artery disease (PCAD) is a neglected clinical entity despite the rising number of cases worldwide. This study aimed to investigate the risk factors of premature coronary artery disease. In this study, we searched articles that had studied the risk factors of premature coronary artery diseases from January 2000 to July 2022 in Saudi Arabia in Web of Science, Pub Med, Scopus, Springer, and Wiley databases. The final analysis is based on seven articles. The smoking prevalence was 39%, diabetes mellitus 41%, hypertension 33%, overweight and obesity 18%, family history of coronary artery disease (CAD) 19%, dyslipidemia 37%, and the prevalence range of low-density lipoprotein cholesterol was 33.8–55.0%. The results revealed a mortality prevalence of 4% ranging from 2 to 8% which is similar to the prevalence in older patients which was 2–10%. Smoking, diabetes mellitus, hypertension, family history of CAD, dyslipidemia, and overweight/obesity are significantly and positively associated with premature coronary artery diseases. The health authorities should design and implement an intensive and effective prophylactic plan to minimize the subsequent impact of PCAD on the young population. In addition, early diagnosis of PCAD has great value in providing timely treatment, managing the patients, and minimizing the burden of the disease.

Has mortality in the United States returned to pre-pandemic levels? An analysis of provisional 2023 data.

The COVID-19 pandemic, which started in 2020, resulted in greater all-cause mortality in 2020 and in subsequent years. Whether all-cause mortality remains elevated in 2023 compared to pre-pandemic numbers is unknown. The United States (US) Center for Disease Control Wide-Ranging, Online Data for Epidemiologic Research database was used to compare mortality rates between 2019 and provisional data for 2022 and 2023. Age-adjusted mortality rates (AAMRs) for all-cause as well as top causes of mortality were collected. Mortality based on subgroups by sex, age, and ethnicity was also collected. All-cause AAMRs between 2018 and 2023 per 100,000 individuals were 723.6, 715.2, 835.4, 879.7, (provisionally) 798.8, and (provisionally) 738.3, respectively, with AAMRs in 2023 remaining above 2019 pre-pandemic levels. Similar trends were noted in subgroups based on sex, ethnicity, and most age groups. Mortality attributed directly to COVID-19 peaked in 2021 as the 3rd leading cause of death and dropped to the 10th leading cause in 2023. Provisional mortality rate trends for 2023 suggest that rates for diseases of the heart increased during the pandemic but appear to have returned to or dipped below pre-pandemic levels. Provisional 2023 all-cause mortality rates in the US have decreased from the 2021 peak associated with the COVID-19 pandemic but remain above the pre-pandemic baseline. Mortality from some conditions, including diseases of the heart, appears to have recovered from the impact of the COVID-19 pandemic.

Using Wearable Sensors and Machine Learning to Assess Upper Limb Function in Huntington's Disease.

Huntington's disease (HD), like many other neurological disorders, affects both lower and upper limb function that is typically assessed in the clinic - providing a snapshot of disease symptoms. Wearable sensors enable the collection of real-world data that can complement such clinical assessments and provide a more comprehensive insight into disease symptoms. In this context, almost all studies are focused on assessing lower limb function via monitoring of gait, physical activity and ambulation. In this study, we monitor upper limb function during activities of daily living in individuals with HD (n = 16), prodromal HD (pHD, n = 7), and controls (CTR, n = 16) using a wrist-worn wearable sensor, called PAMSys ULM, over seven days. The participants were highly compliant in wearing the sensor with an average daily compliance of 99% (100% for HD, 98% for pHD, and 99% for CTR). Goal-directed movements (GDM) of the hand were detected using a deep learning model, and kinematic features of each GDM were estimated. The collected data was used to predict disease groups (i.e., HD, pHD, and CTR) and clinical scores using a combination of statistical and machine learning-based models. Significant differences in GDM features were observed between the groups. HD participants performed fewer GDMs with long duration (> 7.5 seconds) compared to CTR (p-val = 0.021, d = -0.86). In velocity and acceleration metrics, the highest effect size feature was the entropy of the velocity zero-crossing length segments (HD vs CTR p-val <0.001, d = -1.67; HD vs pHD p-val = 0.043, d=-0.98; CTR vs pHD p-val = 0.046, d=0.96). In addition, this same variable showed a strongest correlation with clinical scores. Classification models achieved good performance in distinguishing HD, pHD and CTR individuals with a balanced accuracy of 67% and a 0.72 recall for the HD group, while regression models accurately predicted clinical scores. Notably the explained variance for the upper extremity function subdomain scale of Unified Huntington's Disease Rating Scale (UHDRS) was the highest, with the model capturing 60% of the variance. Our findings suggest the potential of wearables and machine learning for early identification of phenoconversion, remote monitoring in HD, and evaluating new treatments efficacy in clinical trials and medicine.

Lung cancer screening among women Veterans within the Veterans’ Health Administration.

10537 Background: Despite advancements in survival rates, lung cancer remains the leading cause of cancer-related deaths among women in the United States (US). In response to this challenge, the United States Preventive Services Task Force (USPSTF) issued updated guidelines in 2021 to broaden the pool of eligible candidates for lung cancer screening (LCS). Pioneering initiatives, such as the Lung Cancer Screening Demonstration Project (LCSDP) launched by the Veterans Affairs (VA) in 2012, have played a pivotal role in evaluating the feasibility of implementing Low-Dose Computed Tomography (LDCT) at eight Veterans Affairs Medical Centers (VAMC). Subsequently, the program has undergone substantial expansion. Projections within the veteran community indicate a notable increase in the proportion of women veterans, from 11% in 2023 to an anticipated 18% in 2048. However, scant information is currently available regarding the lung cancer screening patterns within this expanding demographic. Methods: Women veterans ages 55 -80, current or former smokers from 2015- 2021 were identified through the VA corporate data warehouse (CDW). ICD 9/10 codes were used to identify women veterans with a lung cancer diagnosis. Diagnoses were verified via chart review. Data were analyzed using R Studio software. Results: Of the women veterans identified (n=44,342), 10,623 received LCS (24%) and 942 (2%) had a primary diagnosis of lung cancer. In the cohort of 942 women diagnosed, 286 (30%) had received lung cancer. Women veterans diagnosed with lung cancer tended to be aged &gt;65 (55%), white (72%), single (72%), unemployed (71%), and urban dwelling (70%) within the southeastern US (35%). Compared to women veterans who did not receive LCS, those who did had higher rates of localized disease (47% vs 34%) and lower rates of metastatic disease (12% vs 19%). Factors associated with higher rates of LCS included mammography (60% vs 49%), a family history of lung cancer (4% vs 2%) and living in the southeastern US (46% vs 35%). It is to be noted that 23% of the women veterans who were screened lived in rural areas and 18.53% identified as black. 98.9% of the women had reported current or former tobacco use but the data on pack year history was missing in 87.6% of charts. Conclusions: While further progress can be made, it is notable that 24% of women veterans received LCS, surpassing national averages. This discrepancy underscores the potential to advance efforts in establishing a comprehensive and structured lung cancer screening initiative, thereby facilitating the equitable inclusion of historically marginalized groups, particularly minorities and rural populations. The findings emphasize the imperative to overcome existing impediments to nationwide enrollment and retention in LCS. Lastly, the study underscores the necessity for increased resource allocation towards tobacco cessation initiatives as an integral component of the broader expansion strategy.

Prevalence and influencing factors of chronic diseases among the elderly in Southwest China: A cross-sectional study based on community in urban and rural areas

ObjectiveTo explore the influencing factors affecting chronic diseases of elderly in Kunming. MethodsData were collected from November 2020 to August 2021.The crosssectional study based on community was adopted. And hierarchical random sampling was used. A face to face questionnaire survey was conducted among the respondents or family caregivers. The contents we collected mainly include general demographic characteristics and other related influencing factors, self-reported chronic diseases and disability status. Results1161 elderly were investigated in total. The percentage of non-communicable chronic disease among the rural elderly was higher than that of urban elderly. Binary logistic regression analysis showed that in urban areas, female (OR: 0.592;95 %CI:0.396 ∼ 0.885), not in marriage (OR:1.643;95 %CI:1.093 ∼ 2.470)and not very satisfied with family support (OR:1.858;95 %CI:1.115 ∼ 3.096) are the influencing factors of chronic disease, while in rural areas are not in marriage (OR:1.961;95 %CI:1.021 ∼ 3.763), more health-promoting behavior (OR:0.582;95%CI:0.350 ∼ 0.970), not very satisfied with family support (OR:1.858;95 %CI:1.115 ∼ 3.096), age 70–79 (OR:1.805;95 %CI:1.705 ∼ 3.031), age 80 and above (OR:2.081;95 %CI:1.010 ∼ 4.288), empty nest family (OR:0.389;95 %CI:0.186 ∼ 0.811)and personal monthly income 2001-3000 (OR:0.353;95CI%:0.180 ∼ 0.693). The influencing factors of urban-rural multimorbidity and non-communicable chronic disease with disability also exist differences at individual, family and social levels. ConclusionsThe prevalence rate of non-communicable chronic diseases among the elderly in Yunnan Province is not optimistic. Personal, family and social factors would affect the non-communicable chronic diseases of the elderly and there exist difference in influencing factor of non-communicable chronic disease between urban and rural areas.

Preoperative radiosurgery for brain metastases (PREOP-1): A feasibility trial

PurposePreoperative radiosurgery (SRS) of brain metastases (BM) aims to achieve cavity local control with a reduction in leptomeningeal relapse (LMD) and without additional radionecrosis compared to postoperative SRS. We present the final results of a prospective feasibility trial of linac-based stereotactic radiosurgery (SRS) prior to neurosurgical resection of a brain metastasis (PREOP-1). MethodsEligibility criteria included a BM up to 4 cm in diameter for elective resection. The primary endpoint was the feasibility of delivering linac-based preoperative SRS in all patients prior to anticipated gross tumour resection. Secondary endpoints included rates of LMD, local control and overall survival. Exploratory endpoints were the level of expression of immunological and proliferative markers. ResultsThirteen patients of median age 65 years (range 41–77) were recruited. Twelve patients (92 %) received preoperative radiosurgery and metastasectomy and one patient went directly to surgery and received postoperative SRS, thus the primary endpoint was not met. The median time between referral and preoperative SRS was 6.5 working days (1–10) and from SRS to neurosurgery was 1 day (0–5). The median prescribed dose was 16 Gy (14–19) to a median planning target volume of 12.7 cm3 (5.9–26.1). Five patients completed 12-month follow-up after preoperative SRS without local recurrence or leptomeningeal disease. The patient who received postoperative FSRT developed LMD after six months. There was one transient toxicity (grade 2 alopecia) and nine patients have died from extracranial causes. Patients reported significant improvement in motor weakness at 6 months (P = 0.04). No pattern in changes of marker expression was observed. ConclusionIn patients with large brain metastasis without raised intracranial pressure, linac-based preoperative SRS was feasible in 12/13 patients and safe in 12/12 patients without any surgical delay or intracranial complications.

Prospective Clinical Follow-Up Results of Infective Endocarditis.

Infective endocarditis incidence has been rising in recent years, with high mortality. Risk factors such as underlying heart diseases, chronic diseases, healthcare-associated infections, advanced age, and intravenous (IV) drug use have gained importance in the incidence, the treatment approach, and the disease course. The aim of this study is to contribute to Türkiye's data on infective endocarditis epidemiology and risk factors. This study examined risk factors, diagnostic and treatment approaches, and prognosis of infective endocarditis cases at Pamukkale University Faculty of Medicine Hospital. It was carried out prospectively for 28 months. During this period, 67 endocarditis cases were detected in 65 patients. Among cardiac diseases, the rate of congenital heart diseases (41%), degenerative heart diseases (37%), and acute rheumatic fever (ARF) related valvular heart disease (31%) were found to be high. Hospitalization in the last six months (53.7%), history of cardiac surgery (41.8%), use of IV catheters (22.4%), hemodialysis (14.9%) and IV drug use (7.5%) were also determined. Staphylococci, streptococci, and enterococci were the primary agents. The most used empirical treatments were ampicillin, ampicillin-sulbactam, and gentamicin. Natural valve endocarditis was most determined. Surgical treatment was applied in 56.7% of endocarditis cases. Septic embolism and cardiac failure were the most common complications. This study's findings regarding the epidemiology and prognosis of infective endocarditis pointed out that it is still a disease with a high mortality rate.

Evaluating the utility of routine survivorship exams in breast cancer: Modality of detection of recurrence in a prospective cohort study.

1629 Background: National Comprehensive Cancer Network surveillance guidelines for invasive breast cancer recommend a history and physical exam every 3-12 months for the first 5 years, followed by annually, and mammography every 12 months. However, frequent in-office visits create time toxicity for breast cancer survivors, may have low utility in recurrence detection, and can create false reassurance. This study evaluates the modality of breast cancer recurrence in an integrated health system with access to primary and specialty care. Methods: We investigated mode of detection of recurrent breast cancer in the Pathways Study, a prospective cohort study of adult women diagnosed with and treated for invasive breast cancer in Kaiser Permanente Northern California, with enrollment from 2006 to 2013, and follow-up through December 2021. In this analysis, we included 4,431 women diagnosed at Stages I-III. Cohort members were followed for recurrences, deaths, and other outcomes. Of primary interest was modality of detection of recurrence, categorized as patient-driven symptoms, surveillance mammogram, diagnostic testing (i.e., other surveillance imaging for recurrence such as PET CT or MRI), routine clinical breast exam, or incidental finding. Results: A total of 617 (13.9%) women were identified as having breast cancer recurrence. Patients with recurrence shared similar demographic characteristics to those without recurrence. The recurrence population had median age of 59.2 years, BMI of 28.2 kg/m2, and racial/ethnic composition of 63% white,13% Hispanic,12% Asian, and 10% black. The median time from diagnosis to recurrence was 4 years. Seventy percent of recurrences were found to have distant metastatic disease, of which only 6.7% had concurrent local nodal and/or breast involvement. For those without metastases, 17.7% had recurrence localized in the ipsilateral breast, 2.8% in both the breast and locoregional nodes, and 9.3% only in locoregional nodes. Most recurrences were detected by patient driven symptoms (69.4%). Among the total cases, 8.1% of patients were diagnosed by routine mammogram, 10.9% with diagnostic testing and 4.5% by incidental finding. Recurrences in 6.8% of patients were detected by routine physician exam. Overall survival for those with recurrence was 31.1% and most deaths were attributed to breast cancer (89%). Conclusions: Our study, the largest investigation of breast cancer recurrence modality of detection in a US community oncology setting with comprehensive care, revealed the majority of recurrences were identified through patient self-detection with only 6.8% detected by physician exam. Most recurrences were distant, underscoring the need for alternative screening modalities to detect metastatic recurrences earlier, especially in the context of emerging treatments and improved survival rates for oligometastatic disease.

Measuring COVID-19's impact on diagnosis of cervical cancer by race/ethnicity, age, and region of the United States.

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race, stage at presentation, and regions of the US. Methods: Data on cervical cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 to calculate estimated and actual incidence rates per 100,000 women. We compared actual cervical cancer incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 245,618 cases of cervical cancer were identified. In 2019, prior to the pandemic, the incidence was 7.64 per 100,000 women. From 2001-2019, cervical cancer incidence decreased by 0.96% per year (p=0.023). Based on this trend, we expected the incidence to be 7.57 per 100,000 women in 2020, but the reported incidence was only 6.83 per 100,000, therefore, there were 9.8% less cervical cancer cases (1,189 cases) in 2020 than expected. This was most noticeable at the lower and upper ends of the age distribution, with 17.6% less cases than expected in the year 2020among 25-29 year-olds and 18.4% less cases than expected among 85+ year-olds. This is in comparison to the median age group for cervical cancer (50-54 year-olds) in whom there were 14.5% (193) less cases than expected in 2020. Based on stage of disease, for local, regional, and distant disease there were 16.3%, 2.8%, and 1.9%, less cases than expected in 2020, respectively. Within racial and ethnic groups, we found that Non-Hispanic Black (NHB) and Hispanic patients had 15.0% and 13.9% less cases than expected, versus 8.7% among Non-Hispanic White (NHW) and 5.8% among Non-Hispanic Asian and Pacific Islander (NHAPI) patients. Comparing U.S. regions, the Midwest, Northeast, West, and South had 14.6%, 10.2%, 10.2%, and 9.0% less cases than expected for 2020, respectively. Conclusions: Our data suggest that the reported cervical cancer cases were significantly less than predicted based on past trends during the COVID-19 pandemic.. Older age, NHB and Hispanic patients, and those residing in Midwest states had the greatest number of possible missed diagnoses of cervical cancer during this time. Mitigating strategies are needed to reinstate screening programs, particularly in these at-risk groups to prevent increased rates of advanced stage disease and mortality.

Disparities by sex in Hispanic patients with cutaneous melanoma: A national database analysis.

e23045 Background: Melanoma is the fifth most common form of malignancy in the United States.1 Studies have established that Hispanic patients have worse melanoma-specific survival compared to non-Hispanic White individuals.2 However, there is a paucity of literature investigating sex differences in patient characteristics and outcomes within Hispanic melanoma patients. Thus, the aim of this study is to further examine sex differences in melanoma characteristics and disease-specific survival within Hispanic patients. Methods: Individuals of Hispanic descent diagnosed with microscopically confirmed cases of cutaneous melanoma (ICD-O-3 codes 8720/3-8780/3; Primary Site codes C44.0-C44.9) between 2000 and 2020 were identified through the Surveillance, Epidemiology, and End Results (SEER) database. Statistical analyses involved Chi-squared tests, Kaplan-Meier and log-rank methods, and multivariate Cox regression, with significance set at a p-value &lt; 0.05. Results: In a cohort of 12,328 Hispanic melanoma patients (43.3% male, 56.7% female), a significant association between sex and age was found (p &lt; 0.001). The greatest proportion of males were in the 60-79 age group (39.7%), while females were predominantly in the 40-59 age group (39.0%). Greater number of males had truncal melanomas (31.4%) compared to females having lower extremity melanomas (35.2%) (p &lt; 0.001). Females exhibited higher rates of localized disease (80.3% vs 70.2%) while males were more frequently diagnosed with regional (18.5% vs 13.8%) and distant disease (11.3% vs 5.9%) (p &lt; 0.001). Males demonstrated greater mean Breslow thickness (1.80 vs 1.44; p &lt; 0.001), elevated rates of lymph node positivity (37.2% vs 27.2%; p &lt; 0.001), and metastatic disease (2.8% vs 1.6%; p &lt; 0.001). On univariate Kaplan-Meier analysis, males demonstrated significantly reduced disease-specific survival (182.9 months) compared to females (214.2 months) (p &lt; 0.001). After adjusting for age, disease stage, annual income, rural vs urban residence, and primary tumor site, male sex independently increased disease-specific mortality compared to females (HR = 1.31; 95% CI 1.16-1.48; p &lt; 0.001). Conclusions: Our investigation reveals that Hispanic males tend to receive melanoma diagnoses at older ages, advanced-stage disease, and primarily on the trunk.3 Furthermore, our study is the first to highlight a significantly reduced disease-specific survival in males compared to females. The observed sex differences may arise from a complex interplay of behavioral factors and immunological, hormonal, or genetic influences.4 Men exhibit a lower likelihood of engaging in skin self-examinations and seeking medical assistance. Limitations to this study include use of data reported through a national database. Nonetheless, this study underscores the significance of sex-specific variations in presentation and disease-specific survival among Hispanic patients.

The association between fatty acids and atherosclerotic diseases: A mendelian randomization study

BackgroundThe current observational studies have disputed the relationship between various fatty acids and atherosclerotic diseases, and the causal relationship between the two is still unclear. MethodsIn this study, we utilized the available genome-wide association studies (GWAS) summary data on fatty acids and atherosclerotic diseases from the IEU OpenGWAS project. After identifying the appropriate single nucleotide polymorphisms (SNPs) as instrumental variables, we employed the MR-PRESSO outlier test to remove extreme values. Subsequently, we conducted a two-sample mendelian randomization (MR) analysis and performed sensitivity analyses to ensure the reliability of the results. ResultsThe results of MR analysis suggest that ratio of saturated fatty acids to total fatty acids is positively correlated with the incidence rate of coronary heart disease (OR = 1.341, 95% CI = 1.016 - 1.769, P value = 0.038), monounsaturated fatty acid levels is negatively correlated with the incidence of stroke (OR = 0.800, 95% CI = 0.642 - 0.996, P value = 0.046), and docosahexaenoic acid levels is negatively correlated with the incidence of peripheral artery disease (OR= 0.747, 95% CI= 0.572 - 0.976, P value= 0.033). All results showed no heterogeneity or pleiotropy, but leave-one-out tests showed that the analysis results of some fatty acids were driven by a single SNP. ConclusionsThis study highlights the existence of causal relationships between fatty acids and atherosclerotic diseases at the genetic level. These findings provide valuable insights for potential prevention measures and therapeutic targets for the three atherosclerotic diseases.

Whole blood transcriptome in long-COVID patients reveals association with lung function and immune response

BackgroundMonths after infection with SARS-CoV-2, at least 10% of patients still experience complaints. Long-COVID is a heterogeneous disease and clustering efforts revealed multiple phenotypes on a clinical level. However, the molecular pathways underlying long-COVID phenotypes are still poorly understood. ObjectivesThis study aims to cluster patients according to their blood transcriptomes and uncover the pathways underlying their disease. MethodsBlood was collected from 77 patients with long-COVID from the P4O2 COVID-19 study. Unsupervised hierarchical clustering was performed on the whole blood transcriptome. These clusters were analysed for differences in clinical features, pulmonary function tests and gene ontology (GO) term enrichment. ResultsClustering revealed two distinct clusters on a transcriptome level. Compared to cluster 2 (n=65), patients in cluster 1 (n=12) showed a higher rate of pre-existing cardiovascular disease (58% vs 22%), higher prevalence of gastrointestinal symptoms (58% vs 29%), shorter hospital duration during SARS-CoV-2 infection (median: 3 vs 8 days), lower Tiffeneau index (72% vs 81%) and lower diffusion capacity of the lung for carbon monoxide (DLCO) (68% vs 85% predicted). GO-term enrichment analysis revealed upregulation of genes involved in the antiviral innate immune response in cluster 1, while genes involved with the adaptive immune response were upregulated in cluster 2. ConclusionThis study provides a start in uncovering the pathophysiological mechanisms underlying long-COVID. Further research is required to unravel why the immune response is different in these clusters, and to identify potential therapeutic targets to create an optimized treatment or monitoring strategy for the individual long-COVID patient.

Associations of ctDNA clearance and pathological response after neoadjuvant treatment in patients with locally advanced oral cancer.

6043 Background: Neoadjuvant treatment (NAT) has improved clinical outcomes in some patients with locally advanced oral squamous cell carcinoma (LAOSCC). Effective biomarkers assessing the treatment response is still lacking. Previous studies have posed the potential of circulating tumor DNA (ctDNA) in monitoring treatment response, but the underlying mechanisms behind non-shedding in tumors remain unclear. Methods: 29 LAOSCC patients received NAT followed by surgery were enrolled. Seven (24.1%), 9 (31%), and 13 (44.8%) patients received NAT of apatinib+camrelizumab, TPF chemoagents, and toripalimab+paclitaxel+cisplatin, respectively. Tumor tissues before NAT underwent whole exome sequencing and whole transcriptome resequencing. Blood samples at pre-NAT (T0), mid-NAT (T1), before surgery (T2) and after surgery (T3) were analyzed using a tumor-informed, personalized NGS assay. Multi-omics analysis, including ctDNA status, was performed with patients' clinical features and outcomes. Results: Among the 29 patients received NAT, the MPR rate was 55.2% (16/29), and the pCR rate was 27.6% (8/29). At baseline(T0), ctDNA was detectable in 25/29 (86.2%) patients, which decreased over time (T1: 77.8%; T2: 51.7%; T3: 6.9%). Persistent ctDNA at T2 indicates a higher rate of residual disease after NAT (100% non-pCR) compared to ctDNA-negative patients (42.8% non-pCR; p = 0.0047). All patients achieving pCR at T2 were ctDNA-negative (n=8, 100%) including 2 non-shedders. The PPV and NPV for predicting pCR by ctDNA clearance at T2 were 57.1% (8/14) and 100% (15/15), respectively. ARSF, CFAP47, or HAUS8 mutations at baseline were associated with significantly higher pCR rates (p&lt;0.05). Four non-shedders with undetectable ctDNA at T0 were significantly enriched in patients with negative lymph nodes, lower clinical T stage, and high CPS score. The non-shedders had significantly lower tumor mutational burden (TMB), higher stromal score and cancer-associated fibroblast (CAF) (p&lt;0.05). Spatial transcriptome analysis further supports that MHC-II pathway-related genes were significantly up-regulated in the non-shedders. The enhancing communication intensity between CAFs, endothelial cells and T cells might provide an anti-cancer immune microenvironment for non-shedders. Conclusions: Our results indicate that the clearance of ctDNA clearance at T2 was associated with an improved pCR rate. Furthermore, our findings shed light on the factors that prevent ctDNA release from oral squamous cell carcinoma.[Table: see text]

Measuring COVID-19's impact on diagnosis of cervical cancer by race/ethnicity, age, and region of the United States.

e17535 Background: The COVID-19 pandemic brought to light significant access-to-care issues for patients across the country, which we hypothesized may have disrupted recent trends in incidence for certain screenable diseases. The goal of this study was to evaluate the impact of the COVID-19 pandemic on cervical cancer incidence based on age, race, stage at presentation, and regions of the US. Methods: Data on cervical cancer incidence were obtained from the United States Cancer Statistics (USCS) program from 2001-2020. We employed SEER*Stat 8.4.1.2 and Joinpoint regression program 5.0.2 to calculate estimated and actual incidence rates per 100,000 women. We compared actual cervical cancer incidence rates in the year 2020 to estimated rates based on trends from the years 2001-2019. Results: From 2001-2020, 245,618 cases of cervical cancer were identified. In 2019, prior to the pandemic, the incidence was 7.64 per 100,000 women. From 2001-2019, cervical cancer incidence decreased by 0.96% per year (p=0.023). Based on this trend, we expected the incidence to be 7.57 per 100,000 women in 2020, but the reported incidence was only 6.83 per 100,000, therefore, there were 9.8% less cervical cancer cases (1,189 cases) in 2020 than expected. This was most noticeable at the lower and upper ends of the age distribution, with 17.6% less cases than expected in the year 2020among 25-29 year-olds and 18.4% less cases than expected among 85+ year-olds. This is in comparison to the median age group for cervical cancer (50-54 year-olds) in whom there were 14.5% (193) less cases than expected in 2020. Based on stage of disease, for local, regional, and distant disease there were 16.3%, 2.8%, and 1.9%, less cases than expected in 2020, respectively. Within racial and ethnic groups, we found that Non-Hispanic Black (NHB) and Hispanic patients had 15.0% and 13.9% less cases than expected, versus 8.7% among Non-Hispanic White (NHW) and 5.8% among Non-Hispanic Asian and Pacific Islander (NHAPI) patients. Comparing U.S. regions, the Midwest, Northeast, West, and South had 14.6%, 10.2%, 10.2%, and 9.0% less cases than expected for 2020, respectively. Conclusions: Our data suggest that the reported cervical cancer cases were significantly less than predicted based on past trends during the COVID-19 pandemic.. Older age, NHB and Hispanic patients, and those residing in Midwest states had the greatest number of possible missed diagnoses of cervical cancer during this time. Mitigating strategies are needed to reinstate screening programs, particularly in these at-risk groups to prevent increased rates of advanced stage disease and mortality.

Epidemiology of Adenosquamous Carcinomas.

Adenosquamous carcinomas (ASCs) are a very rare histology containing cancer cells with both glandular-like (adeno) and squamous cell histologies, comprising typically a fraction of a percent of all solid tumors. The bulk of the literature on ASCs is comprised of case reports and small series, with the general finding that ASCs tend to have worse outcomes than either of their parent histologies. However, there is a lack of pan site-comparative studies in the literature that compare ASC clinicodemographic and survival outcomes with those of conventional adenocarcinomas (ACs) and squamous cell carcinomas (SCCs). In this study, we summarize these outcomes in eight primary sites, comprising 92.7% of all ASC cases diagnosed from 1975 to 2020 in the Surveillance, Epidemiology, and End Results (SEER) database. Lung ASCs comprise 51.5% of all ASC cases, accounting for 1.1% of all lung cancer cases, followed by uterine/cervical cancers at 29.7% of all ASC cases, translating into 1.8% of all cancers in this site. In descending order, the remaining 20% of ASCs arise in pancreatic, oral cavity, biliary, esophageal, colorectal, and gastric sites, comprising between 0.1% and 0.7% of all cancers in these sites. Apart from pancreatic and oral cavity cancers, ASC tumors tended to favor higher rates of regional or distant disease at presentation with poor tumor differentiation compared to either AC or SCC histologies. After multivariable analysis, adjusting for age, sex, detection stage, grade differentiation, surgery, chemotherapy, and radiotherapy, except for oral cavity cancers, ASCs tended to have worse overall survivals compared to ACs (hazard ratios: 1.1 - 1.6) and SCC (1.0 - 1.3), with colorectal ASCs having the worse overall survival compared to colorectal ACs, with a hazard ratio of 1.4 (95% confidence interval: 1.3 - 1.6). Overall, these results suggest that ASC outcomes are site specific, and in general, tend to have worse outcomes than nonvariant ACs and SCCs even after correction for common clinical and epidemiological factors. These cancers have a poorly understood but unique tumor biology that warrants further characterization.