Univariate Statistical Analysis Research Articles

Loneliness in Bavaria before and during the COVID-19 pandemic

Loneliness represents asignificant health risk and is associated with numerous mental and physical conditions. The aim of this paper was to describe the prevalence of loneliness in Bavaria before and during the COVID-19 pandemic with respect to socio-demographic attributes. Data sources were the German Ageing Survey (DEAS) and the Socio-Economic Panel (SOEP). Univariate statistical analyses were carried out for different socio-demographic attributes, such as age, gender, type of household, education, and financial resources. According to the SOEP, the proportion of adults who are often or very often lonely increased from 2.3% in 2017 to 16.2% in 2021. In 2021, women had ahigher prevalence of loneliness than men (21.0% vs. 11.3%), and younger adults had the highest prevalence of loneliness (18 to 25years: 31.7%) compared to the other age groups. During the COVID-19 pandemic, loneliness increased in almost every population subgroup in Bavaria. Further studies are needed to examine whether this development is temporary or represents along-term effect even after the measures to prevent the spread of COVID-19 have been lifted.

Volatile organic compounds in exhaled breath: a promising approach for accurate differentiation of lung adenocarcinoma and squamous cell carcinoma

Lung cancer subtyping, particularly differentiating adenocarcinoma (ADC) from squamous cell carcinoma (SCC), is paramount for clinicians to develop effective treatment strategies. In this study, we aimed: (i) to discover volatile organic compound (VOC) biomarkers for precise diagnosis of ADC and SCC, (ii) to investigated the impact of risk factors on ADC and SCC prediction, and (iii) to explore the metabolic pathways of VOC biomarkers. Exhaled breath samples from patients with ADC (n= 149) and SCC (n= 94) were analyzed by gas chromatography-mass spectrometry. Both multivariate and univariate statistical analysis method were employed to identify VOC biomarkers. Support vector machine (SVM) prediction models were developed and validated based on these VOC biomarkers. The impact of risk factors on ADC and SCC prediction was investigated. A panel of 13 VOCs was found to differ significantly between ADC and SCC. Utilizing the SVM algorithm, the VOC biomarkers achieved a specificity of 90.48%, a sensitivity of 83.50%, and an area under the curve (AUC) value of 0.958 on the training set. On the validation set, these VOC biomarkers attained a predictive power of 85.71% for sensitivity and 73.08% for specificity, along with an AUC value of 0.875. Clinical risk factors exhibit certain predictive power on ADC and SCC prediction. Integrating these risk factors into the prediction model based on VOC biomarkers can enhance its predictive accuracy. This work indicates that exhaled breath holds the potential to precisely detect ADCs and SCCs. Considering clinical risk factors is essential when differentiating between these two subtypes.

Prognostic indicators for canine parvoviral enteritis in a Teaching Hospital in Italy: a retrospective study of 76 cases.

Potential prognostic indicators have been associated with decreased survival during canine parvoviral enteritis (CPE), such as body weight, sex, and clinicopathological parameters. Few studies reported the prognostic factors for CPE in Italy; therefore, the aim of this study was to identify prognostic factors associated with the survival of dogs admitted to the Veterinary Teaching Hospital of Perugia University, naturally infected with canine parvovirus. Seventy-six medical records of dogs with a definitive diagnosis of parvoviral infection admitted from 2017 to 2021 have been reviewed and included in the study. From medical records were extracted data on signalment, history, clinical examination, hematology, serum biochemistry, treatments, progression of clinical signs during hospitalization and outcome. The data have been subjected to univariate and multivariate statistical analysis. Our results showed winter season, male sex, dog ownership, small breed, normal sensory status, normal heart rate, normal hydration status, abdominal pain, increased capillary reperfusion time, and normal white blood cell count as positive prognostic factors. The survival model confirmed that parameters such as male sex, small breed, and ownership increased the survival rate during hospitalization. Data reported in the present study are partially in agreement with previous studies and added new information on the possible prognostic factors in dogs affected by CPE in Italy.

MTORC1 activation in presumed classical monocytes: observed correlation with human size variation and neuropsychiatric disease.

Gain of function disturbances in nutrient sensing are likely the largest component in human age-related disease. Mammalian target of rapamycin complex 1 (mTORC1) activity affects health span and longevity. The drugs ketamine and rapamycin are effective against chronic pain and depression, and both affect mTORC1 activity. Our objective was to measure phosphorylated p70S6K, a marker for mTORC1 activity, in individuals with psychiatric disease to determine whether phosphorylated p70S6K could predict medication response. Twenty-seven females provided blood samples in which p70S6K and phosphorylated p70S6K were analyzed. Chart review gathered biometric measurements, clinical phenotypes, and medication response. Questionnaires assessed anxiety, depression, autism traits, and mitochondrial dysfunction, to determine neuropsychiatric disease profiles. Univariate and multivariate statistical analyses were used to identify predictors of medication response. mTORC1 activity correlated highly with both classical biometrics (height, macrocephaly, pupil distance) and specific neuropsychiatric disease profiles (anxiety and autism). Across all cases, phosphorylated p70S6K was the best predictor for ketamine response, and also the best predictor for rapamycin response in a single instance. The data illustrate the importance of mTORC1 activity in both observable body structure and medication response. This report suggests that a simple assay may allow cost-effective prediction of medication response.

Phytochemical fingerprint revealing antibacterial and antioxidant activities of endemic banana cultivars in Southeast Asia

This study explores the bioactive secondary metabolite profiles of the peels of three major cultivars of bananas (Musa acuminata and Musa balbisiana). These cultivars are primarily grown in Southeast Asia and are widely consumed due to their rich nutritional and fiber content. The research utilizes advanced analytical techniques, specifically HPLC-DAD-q-TOF-MS/MS, in conjunction with both univariate and multivariate statistical analyses, to analyze the ethanolic extracts of the banana peels. This study identifies phenolic acids, flavonoids, and proanthocyanidins as significant contributors to the differentiation of the cultivars. The secondary metabolites rutin, chlorogenic acid, and gentisic acid are pinpointed as the key discriminants. Moreover, the research demonstrates a synergistic contribution of certain phytochemicals to the antioxidant and antibacterial properties of the banana peel extracts. The fingerprint profiling tools introduced in this study offer a reliable method for identifying metabolite biomarkers for the discrimination of banana cultivars.

Usefulness of the 1H NMR Multisuppression Approach for the Global Characterization of Monovarietal Extra-Virgin Olive Oils.

Extra-virgin olive oil (EVOO) is one of the most appreciated vegetable oils worldwide, but its high price makes it prone to suffer adulteration with lower quality oils. Therefore, it is important to have methodologies able to study EVOO composition as a whole in a simple and fast way, in order to guarantee its quality and safety. For this purpose, in this study, commercial samples of five Spanish olive cultivars (Arbequina, Arroniz, Cornicabra, Hojiblanca, Picual) were studied by Proton Nuclear Magnetic Resonance (1H NMR) spectroscopy, using standard and multisuppression pulses. The aim was to explore the possibility of 1H NMR use to characterize in a single run and in a global way the composition of these monocultivar oils, regarding not only their main components (fatty acids supported on triglycerides) but also minor ones (squalene, sterols, diterpenic wax esters of phytol and geranylgeraniol, phenolic and secoiridoid derivatives, like tyrosol, hydroxytyrosol, oleacein, oleocanthal, and lignans, among others, and aldehydes). The use of univariate and multivariate statistical analyses confirmed the presence of compositional features that were specific to some olive varieties. The Arbequina and Arroniz oils showed the most characteristic features that allowed for clearly differentiating them from the others. In contrast, the discrimination between the Cornicabra, Hojiblanca and Picual oils was not so easily achieved.

Lipidomic-Based Algorithms Can Enhance Prediction of Obstructive Coronary Artery Disease.

Lipidomics emerges as a promising research field with the potential to help in personalized risk stratification and improve our understanding on the functional role of individual lipid species in the metabolic perturbations occurring in coronary artery disease (CAD). This study aimed to utilize a machine learning approach to provide a lipid panel able to identify patients with obstructive CAD. In this posthoc analysis of the prospective CorLipid trial, we investigated the lipid profiles of 146 patients with suspected CAD, divided into two categories based on the existence of obstructive CAD. In total, 517 lipid species were identified, from which 288 lipid species were finally quantified, including glycerophospholipids, glycerolipids, and sphingolipids. Univariate and multivariate statistical analyses have shown significant discrimination between the serum lipidomes of patients with obstructive CAD. Finally, the XGBoost algorithm identified a panel of 17 serum biomarkers (5 sphingolipids, 7 glycerophospholipids, a triacylglycerol, galectin-3, glucose, LDL, and LDH) as totally sensitive (100% sensitivity, 62.1% specificity, 100% negative predictive value) for the prediction of obstructive CAD. Our findings shed light on dysregulated lipid metabolism's role in CAD, validating existing evidence and suggesting promise for novel therapies and improved risk stratification.

Efficacy and safety of alfaxalone compared to propofol in canine refractory status epilepticus: a pilot study

IntroductionRefractory status epilepticus (RSE) is defined as seizure activity that is minimally responsive to first- or second-line antiseizure medications. Constant rate infusion (CRI) intravenous propofol (PPF) is commonly used to treat RSE in dogs and cats. The antiseizure activity of alfaxalone (ALF) in RSE has been demonstrated in various experimental studies. This study compared the clinical efficacy and safety of intramuscular administration followed by CRI infusion of ALF with intravenous administration followed by CRI infusion of PPF to treat canine RSE.Materials and methodsThis was a multicenter, prospective, randomized clinical trial of client-owned dogs referred for status epilepticus that did not respond to first- and second-line drugs. Animals with suspected or confirmed idiopathic or structural epilepsy were included. The dogs were randomly assigned to either the PPF or ALF treatment groups and each group received drug CRI infusions for 6 h. Drug dosages were progressively reduced by 25% every hour from the third hour until suspension after 6 h. Patients were classified as responders or non-responders based on the relapse of epileptic seizures during the 24 h therapy infusion or within 24 h of drug suspension. Univariate statistical analyses were performed.ResultsTwenty dogs were enrolled in the study. Ten (10/20) dogs were randomly allocated to the PPF group and 10 (10/20) to the ALF group. Successful outcomes were obtained in six (6/10) patients in the PPF group and five (5/10) patients in the ALF group. Adverse effects were recorded in six (6/10) and three (3/10) animals in the PPF and ALF groups, respectively. No statistically significant differences in outcomes or the presence of adverse effects were observed between the groups.DiscussionThe results of this preliminary study suggest that ALF can be considered a valid and safe alternative to PPF for the treatment of RSE in dogs, with the additional advantage of intramuscular administration. However, caution should be exercised when using these drugs to provide airway and hemodynamic support.

Efficacy and safety of alfaxalone compared to propofol in canine refractory status epilepticus: a pilot study.

Refractory status epilepticus (RSE) is defined as seizure activity that is minimally responsive to first- or second-line antiseizure medications. Constant rate infusion (CRI) intravenous propofol (PPF) is commonly used to treat RSE in dogs and cats. The antiseizure activity of alfaxalone (ALF) in RSE has been demonstrated in various experimental studies. This study compared the clinical efficacy and safety of intramuscular administration followed by CRI infusion of ALF with intravenous administration followed by CRI infusion of PPF to treat canine RSE. This was a multicenter, prospective, randomized clinical trial of client-owned dogs referred for status epilepticus that did not respond to first- and second-line drugs. Animals with suspected or confirmed idiopathic or structural epilepsy were included. The dogs were randomly assigned to either the PPF or ALF treatment groups and each group received drug CRI infusions for 6 h. Drug dosages were progressively reduced by 25% every hour from the third hour until suspension after 6 h. Patients were classified as responders or non-responders based on the relapse of epileptic seizures during the 24 h therapy infusion or within 24 h of drug suspension. Univariate statistical analyses were performed. Twenty dogs were enrolled in the study. Ten (10/20) dogs were randomly allocated to the PPF group and 10 (10/20) to the ALF group. Successful outcomes were obtained in six (6/10) patients in the PPF group and five (5/10) patients in the ALF group. Adverse effects were recorded in six (6/10) and three (3/10) animals in the PPF and ALF groups, respectively. No statistically significant differences in outcomes or the presence of adverse effects were observed between the groups. The results of this preliminary study suggest that ALF can be considered a valid and safe alternative to PPF for the treatment of RSE in dogs, with the additional advantage of intramuscular administration. However, caution should be exercised when using these drugs to provide airway and hemodynamic support.

Identification of Urine Metabolic Markers of Stroke Risk Using Untargeted Nuclear Magnetic Resonance Analysis.

Stroke remains the second leading cause of mortality worldwide, and the third leading cause of death and morbidity combined, affecting more than 12 million people every year. Stroke pathophysiology results from complex interactions of several risk factors related to age, family history, gender, lifestyle, and the presence of cardiovascular and metabolic diseases. Despite all the evidence, it is not possible to fully prevent stroke onset. In recent years, there has been an exploration of innovative methodologies for metabolite analysis aimed at identifying novel stroke biomarkers. Utilizing Nuclear Magnetic Resonance (NMR) spectroscopy, we investigated small molecule variations in urine across different stages of stroke risk. The Framingham Stroke Risk Score was used in people over 63 years of age living in long-term care facilities (LTCFs) to calculate the probability of suffering a stroke: low stroke risk (LSR, control), moderate stroke risk (MSR), and high stroke risk (HSR). Univariate statistical analysis showed that urinary 4-hydroxyphenylacetate levels increased while glycolate levels decreased across the different stroke risk groups, from the LSR to the HSR groups. Trimethylamine N-oxide (TMAO) had average concentration values that were significantly higher in elderly people in the HSR group, while trigonelline levels were significantly lower in the MSR group. These metabolic markers can be used for early detection and to differentiate stages of stroke risk more efficiently.

Interpersonal violence against people with intellectual disabilities in São Paulo, Brazil: characteristics of victims, perpetrators and referrals

IntroductionInterpersonal violence is a phenomenon that can occur with different people and conditions. However, people with intellectual disabilities have increased vulnerability to this problem, with potential risks to their health and well-being. The aim of this study was to identify the sociodemographic characteristics of people with disabilities who have been victims of interpersonal violence, the profile of the perpetrators and the measures taken after the victims have been cared for.MethodsThis is an exploratory, descriptive, cross-sectional study using the Interpersonal Violence Notification Forms entered into the Brazilian Ministry of Health’s Notifiable Diseases Information System. The city of São Paulo was chosen as the setting because it is the largest city in Latin America and has a faster data processing system than other cities. The period covered notifications made between 2016 and 2022. The information was collected between October and November 2023 and a univariate statistical analysis was carried out. Fisher’s exact test was used, with a significance level of 5% (α = 0.05).ResultsThere were 4,603 notifications against people with intellectual disabilities in the period. The forms of physical violence, neglect/abandonment and psychological/moral violence were more frequent in the 15–19 age group, while sexual violence was more frequent in the 10–14 age group (p < 0.001). The sex most often attacked was female in all the forms investigated (p < 0.001) and the skin colors of the most victimized people were black and/or brown, except in cases of neglect/abandonment (p = 0.058). Most of the victims had little schooling (p = 0.012). The aggressions were committed by one person (p < 0.001), known or related to the victim, such as mother or father, except in cases of sexual violence, where strangers were the main perpetrators (p < 0.001). The sex of the perpetrator was male, except in cases of neglect and/or abandonment (p < 0.001), and the age was between 25 and 29 (p = 0.004). In cases of sexual violence, rape was the most frequent and the procedures carried out were blood collection followed by prophylaxis for Sexually Transmitted Infections (STIs) were the main procedures carried out by health professionals (p = 0.004). The majority of referrals made after receiving care were to the health and social assistance network, with few referrals to bodies such as the human rights reference center, guardianship council and police stations (p < 0.001).ConclusionPeople with intellectual disabilities are highly vulnerable to the forms of violence studied, especially children and adolescents, black or brown, with low levels of education. The perpetrators are usually close people, male and older than the victims. The referrals made by health professionals did not prioritize the victim’s safety and the guarantee of human rights. Lines of care for the health of victims of violence should be implemented, taking into account special aspects, such as people with intellectual disabilities, whose search for help can be difficult.

Assessment of diagnostic delay, morbidity, and mortality outcomes in 302 calciphylaxis patients over a 17-year period: A retrospective cohort study

BackgroundCalciphylaxis patients historically have experienced diagnostic challenges and high morbidity, however limited data is available examining these characteristics over time. ObjectiveThe primary goals were to a) investigate factors associated with diagnostic delay of calciphylaxis and b) assess morbidity outcomes. The secondary goal was to provide updated mortality rates. MethodsA retrospective review of 302 adult patients diagnosed with calciphylaxis between January 1, 2006 and December 31, 2022 was conducted. Univariate and multivariate statistical analyses were performed. ResultsNon-nephrogenic calciphylaxis (p=0.0004) and involvement of the fingers (p=0.0001) were significantly associated with an increased diagnostic delay, whereas involvement of the arms (p=0.01) and genitalia (p=0.022) resulted in fewer days to diagnosis. Almost all patients with genitalia, finger, or toe involvement had nephrogenic disease. The number of complications per patient decreased with time, especially for wound infections (p=0.028), increase in lesion number (p=0.012), and recurrent hospitalizations (p=0.020). Updated 1-year mortality rates were 36.70% and 30.77% for nephrogenic and non-nephrogenic calciphylaxis, respectively. LimitationsLimitations include the retrospective nature and data from a single institution. ConclusionDiagnostic delay, particularly in non-nephrogenic calciphylaxis, and complications per patient decreased with time, highlighting the importance of continued awareness to expedite diagnosis. Mortality rates have continued to improve in recent years.

Factors Associated with Alternate Level of Care Status Designation: a Case-Control Study and Model to Optimize Care Trajectories.

As health-care demand is growing, our health-care system will require the optimization of the care trajectories. Patients with an alternate level of care (ALC) status could be a target for flow optimization. We aimed to characterize ALC patients and risk factors for ALC status, and to propose an integrated model to analyze the trajectory of ALC patients and discuss solutions to reduce their burden. A case-control design was used to compare 60 ALC and 60 non-ALC patients admitted to the geriatric unit of the Centre hospitalier de l'Université de Montréal in 2021, collecting medical and sociodemographic data. Based on our model, univariate statistical analyses were computed to compare groups and identify risk factors for ALC status. ALC patients were less independent (22% performed five to six activities of daily living vs. 43%, p = .03). Both groups were comparable in terms of mobility and neurocognitive disorders. ALC patients were more likely to receive a new diagnosis of a neurocognitive disorder or new behavioural or psychological symptoms (37% vs. 15%, p = .008). Up to 25% of ALC patients were admitted despite presenting no active medical condition (vs. 3% of non-ALC patients, p = .002). The optimization of the care trajectory of ALC patients is mainly based on pre-hospital and post-hospital factors. A proportion of ALC admissions might be avoidable with additional investment in home care resources and relocation procedures. Fluidity of ALC trajectory may benefit from improved orientation at discharge procedures. Full optimization of ALC trajectories requires a systemic understanding of the health-care system.

Identification of genes related to PD-L1 expression in non-small cell lung cancer (NSCLC) tumor samples by GFPrint, a machine learning framework (MLF).

e13600 Background: The advent of drugs targeting the PD-1/PD-L1 axis has revolutionized NSCLC treatment. Although promising, individual responses to these therapies can vary among individuals, and research is ongoing to better understand the mechanisms involved in PD1/PD-L1 expression to optimize treatment protocols, and identify which patients are most likely to benefit from these therapies. In this study, Genetic Fingerprint (GFPrint), a MLF, was employed to identify mutations in genes linked to PD-L1 expression in NSCLC tumor samples. Methods: Whole exome sequencing (WES) was run on samples from biopsies of 46 NSCLC patients (histologic subtypes: squamous-cell carcinoma and adenocarcinoma). WES data were encoded using GFPrint, a MLF that generates virtual representations of the tumor exomes in a latent space (LS) defined by the genetic features of the samples. Clusters of patients were identified in such LS based on the genetic similarities of their tumors. Statistical univariate analysis was run to analyze differences in the distribution among both clusters of clinical (age, smoking, and metastatic status) and pathological (histotype and PD-L1 expression) features. The mutational burden (MB) of each cluster was also examined by pathway enrichment analysis (PEA). Results: Two main clusters were identified, C0 (n=16) and C1 (n=17), with 13 unassigned patients. Main differences between clusters were related to histology and PD-L1 expression. C0 included significantly less patients with adenocarcinoma (10/16; 62.5%) compared to CL1 (17/17; 100%) (p-value=.01). In addition, C0 presented more patients expressing PD-L1 (9/16; 56.2%) compared to C1 (3/17; 17.6%) (p-value=.04). Of interest, PD-L1 positivity was significantly higher (p value=.03) in adenocarcinomas of C0 patients (6/10; 60.0%) than those of C1 (3/17; 17.6%). Moreover, C0 adenocarcinomas presented higher levels of PD-L1 expression (6.3+/-9.7 %) than those of C1 (2.3+/-7.5 %) (p value=.06). MB analysis revealed that 1,357 genes were mutated exclusively in C0 patients, and PEA allowed the identification of 3 enriched cancer-related KEGG pathways: HIF-1 signaling, Ca2+ signaling and actin cytoskeleton. Selection of non-silent mutations in these pathways enabled the identification of 10 genes, mostly included in the HIF-1 signaling pathway, with previous data suggesting their involvement in PD-L1 regulation and expression: PIK3R1, HK1, NOS2, NRAS, BRAF, ITGA1, ITGA9, EGLN1, EGLN2 and AKT1, being the first 6 the only ones found in adenocarcinomas. Conclusions: The identified genes deserve further studies to validate them as possible targets of pharmacological intervention concomitant to PD-1/PD-L1 blockade, and also as potential biomarkers for patients’ selection to improve the efficiency of immunotherapy in NSCLC treatment.

Urinary metabolome of infants with colic treated with Lactobacillus reuteri DSM 17938: a pilot randomized trial.

Lactobacillus reuteri DSM 17938 is the only probiotic recommended for treatment of colicky infants, but its mechanism of action is not clear. The study aim was to examine urinary metabolomic fingerprint of colicky breastfed infants before and after 1 month of orally administered Lactobacillus reuteri DSM 17938 or placebo. This randomized, blinded, placebo-controlled clinical trial was carried out with a well-documented probiotic. Thirty-two infants were enrolled, 16 in the probiotic group and 16 in the placebo group. Urine samples were collected from each subject before starting supplementation and at the end of the study period. Metabolomic profiles were obtained using a gas chromatography/mass spectrometry instrument. Subsequently, to compare groups before and after probiotic supplementation, univariate and multivariate statistical analysis were performed. In the L. reuteri treated group all metabolites for all class of nutrients (sugars, amino acids, carboxylic acids) resulted more abundant after the study period. The comparison with a control group (placebo treated), confirmed this effect on urines. The metabolomic analysis of urine samples from infants treated with L. reuteri DSM 17938 allowed to detect some interesting features related to the effect of this treatment on urinary metabolome. To validate the results, a test on a larger cohort is required.

Linking the companion diagnostic function of cancer genome profiling to therapy: Investigation of TMB-high predictors.

e13033 Background: Based on the companion diagnostic function of the Comprehensive Cancer Genome Profiling (CGP) test in Japan, pembrolizumab is the standard treatment for patients with Tumor Mutational Burden (TMB)-high (H) solid tumors. In this report, we attempted to extract predictive factors of TMB-H from CGP test results. Methods: We carried out a retrospective cohort study of 42 patients with malignant breast tumors (excluding circulating tumor DNA in the blood) who underwent CGP testing between June 1, 2019, and November 30, 2023, at our hospital and affiliated institutions. We analyzed the association between clinicopathological factors, the number of analyzed cancer-related gene mutations (SNV, InDel), and TMB-H using univariate and multivariate statistical analysis. Results: Of the 42 cases (27 positive and 15 negative for estrogen receptor (ER), respectively), seven (16.7%) were TMB-H. Samples significantly associated with TMB-H according to univariate analysis were submitted as pathology specimens (non-primary (16.7%) vs. primary (0%), p = 0.011), ER (positive (16.7%) vs. negative (0%), p = 0.044), letrozole (LET) (yes (11.9%) vs. no (4.8%), p = 0.008), and previous treatment (after 6th line (14.3%) vs. before (2.4%), p = 0.041). Multivariate analysis showed that LET had a significant effect on TMB-H in Aromatase inhibitor agents (LET + Anastrozole + Exemestane) (LET: OR, 19.9; 95% CI, 2.2–183.5; p = 0.008) and the number of cancer-related gene mutations (PIK3CA+TP53) were significantly affected (PIK3CA: OR, 3.8; 95% CI, 1.1–13.2; p = 0.032. TP53: OR, 0.08; 95% CI, 0.01–0.66; p = 0.015). Single regression analysis showed a significant association between the number of PIK3CA mutations and LET. (β, 0.31; SE, 0.11; p = 0.008). Conclusions: ER positivity, history of LET use, prior therapy after the 6th line, and submission of pathology specimens from non-primary tumors to CGP testing are predictive factors for TMB-H. In multivariate analysis, the history of LET use and the number of PIK3CA mutations were significantly associated with TMB-H. Research shows that PIK3CA mutations are most frequent in patients who have undergone preoperative endocrine therapy with LET (Breast Cancer Res Treat. 2020 Nov;184(1):123–133.), suggesting that an increased number of PIK3CA mutations due to LET contributed to TMB-H. Although immune checkpoint inhibitors (ICIs) are not indicated for ER-positive breast cancer, TMB-H may be a predictor of ICI efficacy in such cases. The limitations of our research were the small sample size, and the study population only included Japanese. For the next steps needed to continue in this research, clinical trials should take place to test whether TMB-H is a predictor of ICIs in a wider population of ER-positive breast cancer.

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer

BackgroundUnderstanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum.MethodsUltrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards.ResultsMetabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00).ConclusionsTo our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.

Small Hemothoraces Not Drained on Admission: Initial Volume Predicts Need for Intervention.

Unlike large hemothoraces (HTX), small HTX after blunt trauma may be observed without drainage. We aimed to study if there were risk factors that would predict the need for intervention in initially observed small HTX. A retrospective review of patients with blunt traumatic HTX from 2016 to 2022 was performed. Patients with small HTX (pleural fluid volume <400mL on admission chest computerized tomography [CT]) were included. Patients were considered as being "initially observed" if there was no intervention for the HTX within 48hours after admission. Primary outcome was any HTX-related intervention (open, thoracoscopic or percutaneous procedures) occurring after 48hours and up to 6months after injury. Univariable and multivariable statistical analyses were employed. A P-value of <.05 was considered significant. Of 335 patients with HTX, 188 (59.6%) met inclusion criteria. Median (interquartile range) HTX volume was 90 (36-134)ml. One hundred and twenty-seven (68%) were initially observed. Of these, 31 (24%) had the primary outcome. These patients had a larger HTX volume (median, 129 vs 68mL, P = .0001), and number of rib fractures (median, 7 vs 4, P = .0002) compared to those without the primary outcome. Chest-related readmission occurred in 8 (6%) with a median of 20days from injury. Of these, 7 required an HTX-related intervention. Logistic regression analysis found that both the number of rib fractures and HTX volume independently predicted the primary outcome. For small HTX initially observed, number of rib fractures and initial volume predicted delayed HTX-related intervention.

#1836 Post-transplant evolution of kidney grafts from expanded criteria donors with diabetes

Abstract Background and Aims The increase in the number of potential kidney transplant (KT) recipients has led to efforts to increase the donor pool, including organs from expanded criteria donors (ECD) with diabetes mellitus (DM). However, doubts persist about their viability, especially with DM donors. Our aim is to analyze the post-transplant evolution of KT patients who have received kidney grafts from ECD with or without DM. Method Retrospective observational study of KT who received ECD kidney graft in our center between January 2014 and November 2023. We divided KT patients into two groups based on donor DM; ECD with DM and ECD without DM. We analyzed baseline characteristics and post-KT evolution. Univariate and multivariate statistical analysis was performed using Cox regression (SPSS Statistics 29.0). Results During the study period, 161 patients received grafts from ECD at our center. Pre-implant biopsies were performed on all grafts, with 15 discarded due to high histological score. Of these, 13 (86%) were diabetic donors (p &amp;lt; 0.001). The mean age of donors was 66 years, and that of recipients was 61. Forty-three (26%) KT recipients had a diabetic donor. Clinical characteristics of patients are reflected in Table 1. Conclusion Donors with DM showed adequate survival in our experience, similar to that of other ECD. This may be due to a more stringent pre-transplant clinical selection or pre-KT histological assessment. The development of new techniques is necessary to more precisely asses the viability of these grafts pre-KT, allowing for an increased utilization.

Design, Synthesis, Antitumor Activity and NMR-Based Metabolomics of Novel Amino Substituted Tetracyclic Imidazo[4,5-b]Pyridine Derivatives.

Newly prepared tetracyclic imidazo[4,5-b]pyridine derivatives were synthesized to study their antiproliferative activity against human cancer cells. Additionally, the structure-activity was studied to confirm the impact of the N atom position in pyridine nuclei as well as the chosen amino side chains on antiproliferative activity. Targeted amino substituted regioisomers were prepared by using uncatalyzed amination from corresponding chloro substituted precursors. The most active compounds 6 a, 8 and 10 showed improved activity in comparison to standard drug etoposide with IC50 values in a nanomolar range of concentration (0.2-0.9 μM). NMR-based metabolomics is a powerful instrument to elucidate activity mechanism of new chemotherapeutics. Multivariate and univariate statistical analysis of metabolic profiles of non-small cell lung cancer cells before and after exposure to 6 a revealed significant changes in metabolism of essential amino acids, glycerophospholipids and oxidative defense. Insight into the changes of metabolic pathways that are heavily involved in cell proliferation and survival provide valuable guidelines for more detailed analysis of activity metabolism and possible targets of this class of bioactive compounds.