Multifactorial Analysis Research Articles

Beta 2-microglobulin is an independent risk marker of acute kidney injury in adult patients with hemophagocytic lymphohistiocytosis.

The role of beta2-microglobulin (β2-MG) in predicting acute kidney injury (AKI) in hemophagocytic lymphohistiocytosis patients has been poorly studied. This study aimed to analyze the clinical characteristics of hemophagocytic lymphohistiocytosis patients and identify risk factors that predict AKI development. This retrospective observational cohort study conducted ata single-centerinvolved 938 patients diagnosedwith hemophagocytic lymphohistiocytosis, who were divided into AKI groupand non-AKI group. Patient data were collected and analyzed usingunivariate and multivariate binary logistic regression to identify potiential risk factors associated with AKI occurrence. RESULTS: Among the enrolled patients, 486 were male (51.9%), the median age was 37years (interquartile range, 28.0, 52.0), 58.4%experienced AKI. Mechanical ventilation (8.0% vs. 0.8%) and vasopressor support (21.7% vs. 4.1%) occurred at significantly higher rates in the AKI group compared to the non-AKI group, with significantly higher in-hospital mortality (5.5% vs. 1.3%) and 28-day mortality (12.8% vs. 5.4%). When β2-MG was used as a continuous variable, multifactorial analysis showed that β2-MG, transplantation, and vasopressor support were independently associated with risk for the development of AKI. The incidence ofmorbidity and mortality in patients with hemophagocytic lymphohistiocytosis complicated by AKIremains high. Monitoring levels ofβ2-MG may provide clinicians with timely indicatorsofchanges in renal function, facilitating adjustments to treatment strategies.

The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment

BackgroundThe systemic inflammatory response index (SIRI) is a novel inflammatory-immune biological marker that has prognostic value in various cardiovascular diseases. This study aims to investigate the relationship between SIRI and short-term and long-term prognosis in patients with acute type A aortic dissection (AAAD) underwent surgical treatment.MethodsWe conducted a retrospective analysis of patients with AAAD who underwent emergency surgical treatment at our center. Through multifactorial logistics regression analysis and cox proportional hazards regression analysis, we identified SIRI as an independent risk factor for major adverse events (MAEs) and long-term aorta-related adverse events (ARAEs) post-surgery. The optimal cutoff value of preoperative SIRI was determined using receiver operating characteristic (ROC) curve analysis, and patients were divided into low SIRI group and high SIRI group. The prognostic outcomes at different time points post-surgery for the two groups of patients were analyzed using Kaplan-Meier survival analysis, and the significance was determined by log-rank test.ResultsA total of 691 AAAD patients were included in this study. Among them, 50 patients (7.2%) died within 30 days post-surgery, and 175 patients (25.3%) experienced MAEs. A total of 641 patients were followed up, with an average follow-up time of 33.5 ± 17.5 months, during which 113 patients (17.6%) experienced ARAEs. The results of multifactorial logistics regression analysis and cox proportional hazards regression analysis showed that SIRI was an independent risk factor for postoperative MAEs (OR=3.148, 95%CI[1.650-6.006], p<0.001) and ARAEs (HR=2.248, 95%CI[1.050-4.809], p<0.037). Kaplan-Meier analysis demonstrated that the MAEs-free survival in the high SIRI group was significantly lower than that in the low SIRI group, and a similar trend was observed in the ARAEs-free survival during follow-up (log-rank test, p<0.001).ConclusionPreoperative SIRI is significantly associated with the short-term and long-term prognosis of AAAD patients underwent emergency open surgery, demonstrating its valuable prognostic value. Therefore, preoperative SIRI is a reliable biological marker that can serve as a valuable tool for preoperative risk stratification and decision management.

Association between tenofovir plasma trough concentrations in the early stage of administration and discontinuation of up to five years tenofovir disoproxil fumarate due to renal function-related adverse events in Japanese HIV-1 infected patients

BackgroundThe relationship between plasma tenofovir (TFV) concentration at the beginning of tenofovir disoproxil fumarate (TDF) administration and the development of renal dysfunction during long-term administration of TDF has not been demonstrated yet. The objective of the present study was to determine whether plasma TFV trough concentrations during early TDF administration could serve as an indicator of renal dysfunction when TDF is administered for long periods.MethodsWe included 149 HIV-1 infected Japanese patients who were prescribed TDF. We investigated the relationship between plasma TFV trough concentrations and the rate of discontinuation due to the development of renal dysfunction for up to five years after the start of TDF administration. We also examined how the decrease in renal function over time due to TDF administration was related to factors associated with high TFV levels and plasma TFV trough concentrations.ResultsThe median TFV trough concentration in the TDF discontinuation group was 88 ng/mL, which was significantly higher (p = 0.0041), than that in the continuation group (72 ng/mL). Further, using an ROC curve, the cut-off value for TFV trough concentration at which TDF discontinuation was significantly high was found to be 98 ng/mL. Logistic multivariate analysis of factors associated with discontinuation of TDF due to renal function-related adverse events showed that being ≥ 50 years old (OR = 2.96; 95% CI, 1.01–8.64), having eGFR < 80 mL/min/1.73m2 at the start of TDF administration (OR = 5.51; 95% CI, 1.83–17.5), and TFV trough concentration ≥ 98 ng/mL (OR = 2.96; 95% CI, 1.16–7.60) were independent factors.ConclusionsThe results suggested that the importance of measuring TFV concentrations to evaluate the risk of developing renal function-related adverse events during long-term TDF administration.

Self-care ability and associated factors in community-dwelling older adults living with oral frailty using the COM-B model.

Self-care can improve overall oral health. However, few studies have investigated this in community-dwelling older adults with oral frailty. The Capability, Opportunity, Motivation and Behaviour (COM-B) model may be an appropriate framework to identify factors that affect self-care ability. The purpose of this study was to investigate the current status of and factors influencing self-care ability in community-dwelling older adults living with oral frailty, and to analyse the risk factors of low self-care ability. Two hundred seventy-five community-dwelling older adults with oral frailty participated in this cross-sectional study from October 2022 to March 2023. Participants underwent evaluations of oral health knowledge and behaviour, oral health literacy, nutritional condition, social support, oral health-related quality of life, self-efficacy and self-care ability using questionnaires. The self-care ability of older adults was assessed using the Chinese version of self-care ability scale for the elderly (SASE). The influencing factors were evaluated by single-factor analysis, correlation analysis and multi-factor analysis. Furthermore, we conducted additional analysis, wherein self-care ability was analysed as a categorical variable. Of the participants, the SASE score was 62.43 ± 7.33, and 73.09% were inadequate at self-care ability. There was a positive correlation between the level of self-care ability and each variable (p < .001). Multiple linear regression showed that health literacy (p < .001), age (p < .001), nutritional condition (p = .001), gender (p = .003), quality of life (p = .014) and self-efficacy (p = .040) were significantly associated with decreased self-care ability (R2 = 0.444, F = 19.241). Binomial logistic regression analysis showed that gender, educational level, nutritional condition, oral health literacy and quality of life (all P<0.05) were risk factors for developing low levels of self-care ability. This study suggests that health literacy, age, nutritional condition, quality of life, gender and self-efficacy are important factors that influence self-care ability in community-dwelling older adults living with oral frailty.

Exploring the Impact of Campus Landscape Visual Elements Combination on Short-Term Stress Relief among College Students: A Case from China

Although the effect of campus landscape space on stress relief among college students has been confirmed, few existing studies have considered the impact on stress recovery from the perspective of factor combination, and the key visual elements and the most effective combination of visual elements to relieve stress are still unclear. This study attempts to conduct a natural experiment within Chinese campuses, measuring physiological indicators of stress such as heart rate (HR), frequency domain index of heart rate variability (LF/HF), skin conductance level (SCL), skin temperature (SKT), and respiratory rate (RESP) using physiological instruments. It explored the effects of visual elements and their combinations in campus landscape spaces on short-term stress relief among college students through semantic segmentation, multifactorial analysis of variance, and post hoc multiple comparison methods. Research results demonstrate that the presence of water elements in the field of vision can effectively improve the stress relief effects of landscape spaces. Reasonable combinations of natural landscape elements and artificial landscape elements in the design can also effectively promote stress relief among students. Building facade area and sky area, water area and sky area, and plant species and pavement area are three combinations of factors with the strongest interactive effects. “Natural water scenery” and “exquisite artificial” are two campus landscape design patterns most conducive to short-term stress relief.

[Analysis of the Spatiotemporal Distribution of Algal Blooms and Its Driving Factors in Chaohu Lake Based on Multi-source Datasets].

Eutrophication and harmful algae blooms are one of the common ecological and environmental problems faced by freshwater lakes all over the world. As a typical inland freshwater lake, Chaohu Lake exhibits a high level of eutrophication and algae blooms year-round and shows a spatiotemporal difference in different regions of the lake. In order to understand the basic regularity of the development and outbreak of algal blooms in Chaohu Lake, the data from the comprehensive water observation platform and remote sensing were integrated to obtain the spatiotemporal distribution of algal blooms from 2015 to 2020. Then, an evaluation model based on Boosted Regression Trees (BRT) was constructed to quantitatively assess the importance and interactions of various environmental factors on algal blooms at different stages. The results indicated that:① The occurrence of algal blooms in Chaohu Lake exhibited significant seasonal variations, with the cyanobacteria beginning to recover in spring and bring about a light degree of algal blooms in the western and coastal areas of Chaohu Lake. The density of cyanobacteria reached its maximum in summer and autumn, accompanied by moderate and severe degrees of algal bloom outbreaks. ② During the non-outbreak period, the variation in the cyanobacteria density was greatly affected by physical and chemical factors, which explained 80.3% of the variance in the change in cyanobacteria density. The high concentrations of dissolved oxygen content in the water column and the weak alkalinity (7.2-7.6) and appropriate water temperature (about 3℃) provided a favorable environmental condition for the breeding and growth of cyanobacteria. In addition, the onset of algal blooms was closely related to the air temperature steadily passing through the threshold. According to the statistics, the date of first outbreak of algal blooms in Chaohu Lake was 11 days or so after the air temperature steadily remained above 7℃. ③ During the outbreak period, the occurrence of algal blooms was influenced by the combination of cyanobacterial biomass and meteorological conditions such as temperature, wind speed, and sunshine duration. The cumulative contribution ratio of the four factors was as high as 95%, and each factor had an optimal interval conductive to the outbreak of algal blooms. Furthermore, the results of multi-factor interaction analysis indicated a larger probability of the outbreak of algal blooms in Chaohu Lake under the combined effect of high cyanobacteria density, suitable temperature, and the breeze. This study analyzed and revealed the spatiotemporal characteristics and the dominant influencing factors of algal blooms in Chaohu Lake at different stages, which could provide the scientific basis for the prediction, early warning, and disposal of algal blooms under the context of climate change.

Risk Factors of Chemotherapy-Induced Thrombocytopenia After Oxaliplatin-Containing Chemotherapy for Gastrointestinal Malignancies.

Thrombocytopenia is among the most common chemotherapy-related hematologic toxicities. We aim to determine the predictors of oxaliplatin chemotherapy-induced thrombocytopenia in patients with gastrointestinal tumors to guide the clinic. Clinical data of 750 patients with a malignant gastrointestinal tumor were included as the primary cohort. Basic clinical data, serological indices, and anthropometric indices of these patients were collected. According to the presence or absence of CIT, univariate analysis was performed to identify significant factors for multivariate analysis. In R language software, nomogram was constructed based on the results of multi-factor analysis, and the calibration curve and ROC curve were drawn. Univariate analysis identified 17 factors as closely related to CIT occurrence, namely age, lymph node metastasis (N) stage, metastasis (M) stage, lung metastasis, other site metastasis, chemotherapy regimen, course of treatment, total dose of oxaliplatin, AST, albumin, neutrophils, monocytes, baseline platelets, transferrin, natural killer (NK) cell, phase angle, and SMI (P < 0.10). The binary logistic multivariate regression analysis revealed five independent risk factors for developing CIT (P < 0.05), including the M stage, total dose of oxaliplatin, albumin, baseline thrombocyte count, and NK cell. Based on the results of multivariate logistic regression analysis, R software was used to establish a nomogram model. The calibration curve shows that the combined predictor has good consistency. The area under the ROC curve was 0.877 and the best cut-off value was 0.3579613 (sensitivity, 78.9%; specificity, 81.8%), which showed the better prediction efficiency. The total dose of oxaliplatin, M stage, albumin, baseline platelet count, and NK cell was independent risk factors for CIT. The sequentially constructed histogram model had a good predictive effect on the risk of thrombocytopenia caused by oxaliplatin chemotherapy in patients with gastrointestinal malignancies.

Perceptibility and acceptability of lightness difference of a single maxillary central incisor.

The aim of this study was to assess the lightness difference perceptibility and acceptability thresholds, for a single maxillary central incisor, and to investigate possible differences in these thresholds regarding the direction (+ΔL* vs. -ΔL*), the observer group (dentists vs. laypersons), and the gender and age of the observers. A series of images with varying lightness (L*), were created by altering the right maxillary central incisor of a male Caucasian, on a frontal view full-portrait image. Digital modification of one central incisor by 1 ΔL* unit resulted in 15 different images: one control, seven with increased and seven with decreased lightness. The images were presented in random order, on a digitally calibrated monitor, to 158 observers, grouped into 79 dentists, and 79 laypersons, who were asked to evaluate every image and answer whether they perceive a difference and if yes, whether they accept this difference. A multifactorial analysis of covariance was performed to analyze the perception and acceptance of any difference in the central incisors and to estimate the thresholds. The statistical significance level was α = 0.05. Overall, the magnitude of ΔL*, direction of ΔL*, observer group and age were each significant (p < 0.001), as was gender (p = 0.03). The effect of the magnitude of ΔL* interacted with its direction and the observer group (p = 0.045), and the effect of age interacted with the direction of ΔL*, and the gender and the group of the observers. Estimated 50%:50% perceptibility thresholds ranged from 0.1 to 2.7, and 50%:50% acceptability thresholds ranged from 2.3 to 4.5. Overall, dentists perceived lightness differences at lower magnitudes than laypersons; difference in lightness was perceived and accepted at lower magnitudes when the tooth become lighter instead of darker; and female observers perceived and accepted lightness differences at lower magnitudes compared to males. As age increased overall, differences of lightness were perceived and accepted at higher magnitudes. Perceptibility and acceptability of lightness differences of a single maxillary central incisor are affected by the magnitude and the direction of lightness change, as well as the gender, the age, and the type of the observers. Even small changes in lightness are perceivable; however, thresholds of perception and acceptance are dependent on the magnitude and the direction of change and are also dependent on the observer, with women, dentists and younger people perceiving and accepting changes at lower magnitudes of ΔL*.

Exploring the causes of the prevalence of vancomycin-resistant Enterococcus faecalis

BackgroundBacterial drug resistance represents a significant global concern, with vancomycin-resistant Enterococcus faecalis posing a particularly grave threat to contemporary healthcare systems. This study aims to reveal the reasons for the prevalence of VRE in China.MethodsThis study collected data from the China Antimicrobial Resistance Detection System, China Statistical Yearbook, and China Meteorological Network. The collected data are meticulously organized and subjected to both single-factor and multi-factor analyses. An accurate multiple linear regression model was developed by utilizing this comprehensive dataset.ResultsSingle-factor analysis revealed significant regional variations in the resistance rate of vancomycin-resistant Enterococcus faecalis (P = 0.003). Specifically, there were noteworthy disparities observed between regions experiencing temperate and monsoon climates (P = 0.029; P = 0.005). Furthermore, multi-factor regression analysis demonstrated a negative correlation between the drug resistance rate and both rainfall and rGDP, while a positive correlation was observed with nPI.ConclusionWe successfully established a prediction model for the VRE and found that the resistance rate was low in areas with high rainfall and high per capita economic income, but high in areas with many specialized public health institutions. This is critical for public health strategies and helps policymakers and healthcare practitioners tailor antibiotic resistance approaches to local geography, meteorology, economic conditions.

Construction of a prognostic model for autophagy in Wilm's tumor.

Wilm's tumor (WT) is one of the most common childhood urological tumors, ranking second in the incidence of pediatric abdominal tumors. The development of WT is associated with various factors, and the correlation with autophagy is currently unclear. To develop a new prognostic model of autophagy-related genes (ATG) for WT. Using the Therapeutically applicable research to generate effective treatments (TARGET) database to screen for differentially expressed ATGs in WT and normal tissues. ATGs were screened for prognostic relevance to WT using one-way and multifactorial Cox regression analyses and prognostic models were constructed. The risk score was calculated according to the model, and the predictive ability of the constructed model was analyzed using the ROC (receiver operating characteristic) curve to verify the significance of the model for the prognosis of WT. Sixty-eight differentially expressed ATGs were identified by univariate Cox regression analysis, and two critical prognostic ATGs (CXCR4 and ERBB2) were identified by multivariate Cox regression analysis. Patients were divided into high-risk and low-risk groups according to the differential expression of these two ATGs. Kaplan-Meier (KM) curves showed a significant difference in survival time between the two groups. The critical prognostic ATGs were combined with race, age, and stage in a multifactorial regression analysis, and the final prognostic model was produced as a line graph. The prognostic model of autophagy-related genes composed of the CXCR4 gene and ERBB2 gene has a specific predictive value for the prognosis of WT, and the present study provides a clear basis for future research on biomarkers and therapeutic targets.

Analysis of clinical features and prognostic factors in Takayasu arteritis involving pulmonary hypertension: A retrospective study.

Multiple takayasu arteritis (TA) is a chronic nonspecific large to medium vasculitis disease that mainly accumulates the aorta and its branches. Pulmonary vascular disease is often seen as stenosis and occlusion, and patients may show no moderate to severe pulmonary hypertension (PH). This study aims to summarize the clinical characteristics and analysis of prognostic factors in patients with PH caused by TA. Patients diagnosed with aortitis involving the pulmonary artery by pulmonary arteriography or pulmonary artery and total aortic computed tomography arteriography (CTA). All patients underwent detailed clinical assessment, laboratory data collection, and analysis of imaging data. Patients were followed up and factors affecting the prognosis of the pulmonary arteries were analyzed. Most of the patients' complaints were chest tightness, shortness of breath, decreased activity tolerance, hemoptysis and chest pain. 56.90% of the patients were in at the time of admission. Echocardiographic estimation of pulmonary artery systolic pressure was 90.39 ± 22.87 mm Hg. In terms of laboratory tests, 39.66%% of the patients had elevated C-reactive protein and erythrocyte sedimentation rate, and amino-terminal natriuretic peptide precursor on admission. In terms of imaging, all patients had pulmonary artery involvement, which was combined with aortic involvement in 31.03%. Nuclide lung perfusion/ventilation imaging of the patients revealed multiple perfusion defects/absences in the segmental and subsegmental distribution of the lungs. Univariate Cox regression model analysis suggested that patients' WHO functional class at admission, age ≧ 51 years at the time of consultation, and amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL were factors affecting the prognosis. Further multifactorial Cox regression model analysis suggested amino-terminal natriuretic peptide precursor ≧ 3500 pg/mL was an independent predictor of poor prognosis with a hazard ratio (HR) value of 5.248. Electrocardiogram and echocardiogram may suggest an increased right heart load; some patients have elevated serum inflammatory indexes. Characteristic imaging manifestations include widening of the main pulmonary artery, multiple pulmonary segmental and subsegmental stenoses.

A Prognostic Model Based on the Log Odds Ratio of Positive Lymph Nodes Predicts Prognosis of Patients with Rectal Cancer.

This study aimed to compare the prognostic value of rectal cancer by comparing different lymph node staging systems, and a nomogram was constructed based on superior lymph node staging. Overall, 8700 patients with rectal cancer was obtained from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. The area under the curve (AUC), the C index, and the Akaike informativeness criteria (AIC) were used to examine the predict ability of various lymph node staging methods. Prognostic indicators were assessed using univariate and multivariate COX regression, and further correlation nomograms were created after the data were randomly split into training and validation cohorts. To evaluate the effectiveness of the model, the C index, calibration curves, decision curves (DCA), and receiver operating characteristic curve (ROC) were used. We ran Kaplan-Meier survival analyses to look for variations in risk classification. While compared to the N-stage positive lymph node ratio (LNR), the log odds ratio of positive lymph nodes (LODDS) had the highest predictive effectiveness. Multifactorial COX regression analyses were used to create nomograms for overall survival (OS) and cancer-specific survival (CSS). The C indices of OS and CSS for this model were considerably higher than those for TNM staging in the training cohort. The created nomograms demonstrated good efficacy based on ROC, rectification, and decision curves. Kaplan-Meier survival analysis revealed notable variations in patient survival across various patient strata. Compared to AJCC staging, the LODDS-based nomograms have a more accurate predictive effectiveness in predicting OS and CSS in patients with rectal cancer.

Radiological Features for Predicting the Status of CD8-Positive Lymphocytes in HER2 Positive Breast Cancer.

The level of tumor-infiltrating lymphocytes (TILs) in human epidermal growth factor receptor type 2 (HER2)-positive breast cancer (BC) is positively correlated with pathological complete response. To investigate the relationship between ultrasound (US) and magnetic resonance imaging (MRI) features and the level of CD8-positive TILs (CD8+-TILs) in patients with HER2-positive BC. Retrospective cohort study. This retrospective study included 155 consecutive women with HER2-positive BC. Patients were divided into two groups: CD8+-TILlow (< 35%) and CD8+-TILhigh (≥ 35%) groups. US and MRI features were evaluated using the BI-RADS lexicon, and the apparent diffusion coefficient (ADC) value was calculated using RadiAnt software. Univariate and multivariate analyses revealed the optimal US and MRI features for predicting CD8+-TIL levels. Receiver operating characteristic analysis and the Delong test were used to compare the diagnostic performance of US and MRI features. Furthermore, implementing a nomogram will increase clinical utility. Univariate analysis of US features showed significant differences in shape, orientation, and posterior echo between the two groups; however, there were no significant differences in margins, internal echo, and microcalcification. Multifactorial analysis revealed that shape, orientation, and posterior echo were independent risk factors, with odds ratios of 11.62, 2.70, and 0.16, respectively. In terms of MRI features, ADC was an independent predictor of CD8+-TIL levels. These three US features and the ADC performed well, with area under the curve (AUC) values of 0.802 and 0.705, respectively. The combination of US and ADC values had higher predictive efficacy (AUC = 0.888) than either US or ADC alone (p = 0.009, US_ADC vs. US; p < 0.001, US_ADC vs. ADC). US features (shape, orientation, and posterior echo) and ADC value may be a valuable tool for estimating CD8+-TIL levels in HER2-positive BC. The nomogram may help clinicians in making decisions.

Abstract PO1-02-14: Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort

Abstract Background Compared to middle-aged women, older women have a higher risk of breast cancer death. Whether the increased risk of breast cancer death is present in all subgroups of older adults with breast cancer, or negligible in the subgroups receiving adequate surgical and oncological treatment, has been debated. We studied long-term prognosis by age and subtype, adjusting for stage, treatment, socioeconomic status and comorbidity, clarifying which subgroups of older patients that are at increased risk of breast cancer death. Methods In a nation-wide cohort of 45,949 women aged ≥60 years at diagnosis of breast cancer 1997-2014, we estimated crude probabilities of breast cancer death and from other causes using competing risk methods. Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) with 95% confidence intervals (CI. Results In this large population-based cohort study of older women with breast cancer, we found an increasing risk of breast cancer death with increasing age at diagnosis, both at 5- and 10-year follow up. The strong association between age and breast cancer death was found for all breast cancer subtypes, being most prominent in Her2-positive breast cancer. The age effect was also significant in Luminal A breast cancer where treatment opportunities are not necessarily affected by age. High-risk tumors were equally common in all age groups above 60 years. In multivariable analysis, stage, subtype, grade and treatment were important explanatory variables to the age-related differences in survival, while comorbidity and socioeconomic status contributed minorly. After adjustments, older age remained an independent risk factor for both overall and breast cancer survival. Older women with triple-negative (60-79 years) or Her2-positive (60-84 years) tumors had a 5-year risk of breast cancer death exceeding the risk of death by other causes. Conclusions Older women had a significantly higher risk of breast cancer death irrespective of breast cancer subtype, also in Luminal A disease where treatment opportunities are not necessarily affected by age. Table 3. Crude probabilities of breast cancer specific death and death by other cause (competing cause of death) at 5, 10 and 15 years. Table 4. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) Table 5. Multivariable analysis of prognostic factors affecting 15-year overall (OS) and breast cancer- specific survival (BCSS) by age at diagnosis and subtype. Citation Format: Amelia Chiorescu, Anna L V Johansson, Antonis Valachis, Alexios Matikas, Jan Frisell, Lars Holmberg, Irma Fredriksson. Breast cancer in older women - long-term prognosis by age and subtype in a large population-based cohort [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-02-14.

Abstract PO3-02-13: Breast Cancer in Very Young Adult Women At or Under the Age of 35 Years: Characteristics and Outcomes

Abstract Background: Breast cancer (BC) is the most common malignancy among women in Saudi Arabia. Noticeably, it shows a higher incidence in younger age groups than what is reported from Western countries. Age 35 years and less is an applied cut-off age for clinically defining BC in very young women (BCVY). This study describes characteristics, survival and risk of death associated factors in this rare subset of patients. Methods: A retrospective cohort study included females &amp;gt; 18 and &amp;lt; 35 years with histologically confirmed primary non-metastatic breast cancer from an academic hospital in Jeddah, Saudi Arabia between the years 2009-2019. Demographic data, tumor clinicopathological features, and outcomes were obtained. Survival and potential associated factors were examined. A p-value of less than 0.05 was regarded as statistically significant. Results: 204 female patients with a confirmed breast cancer diagnosis were included. The mean age at diagnosis was 31.43 ± 2.94 years. Fifty-three percent of the patients had a left-sided tumor with the majority being IDC (92%) and one-third with positive axillary lymph nodes (N+) and multifocal disease in 17%. One-quarter of the tumors showed LVI, 45% revealed associated DCIS and 26% showed tumor necrosis on histopathology examination. The presence of tumor-infiltrating lymphocytes (TILs) was reported in 23% of TNBC cases. Tubular differentiation score 3 was reported in 79.4%, nuclear pleomorphism score 3 in 79% and mitosis activity score 3 in 19% while the most reported overall grade was II in 48.5% followed by grade III in 34%. HER2-positive in 33.8 %, HR-positive in 34.3 %, TNBC in 24% and unknown in 8% of the patients. Thirty percent had a distant recurrence and 15% were deceased. The mean survival time was 4.61 years with a maximum of 6.54 years and a minimum of 3.67 years. Table 1 shows the multivariate logistic regression analysis of factors influencing the risk of death in very young patients with breast cancer. Conclusions: The current study describes the clinicopathological characteristic, survival and related factors of breast cancer in very young patients &amp;lt; 35 years, which is considered an uncommon presentation. Large, high-grade tumors and a high frequency of HER2 and TNBC were observed in BCVY patients. Involvement of the regional lymph nodes and the development of distant recurrence were associated significantly with an increased risk of death. The presence or absence of TILs, LVI and tumor necrosis on histopathological examination did not influence the risk of recurrence or death in this cohort. Table 1. The multivariate logistic regression analysis of factors influencing the risk of death in very young patients with breast cancer. Citation Format: Atlal Abusanad, Rana Ajabnoor, Aydah Al-Awadhi, Omalkhair Abualkhair. Breast Cancer in Very Young Adult Women At or Under the Age of 35 Years: Characteristics and Outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-13.

Abstract PO1-12-06: Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia?

Abstract Background: Febrile neutropenia (FN), a major hematologic adverse event in perioperative chemotherapy for breast cancer, is more prevalent among Asians than in Caucasian populations. Four main guidelines, i.e., ASCO, EORTC, NCCN, and ESMO, provide recommendations regarding the appropriate use of hematopoietic growth factors. These guidelines recommend primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) based on the estimated incidence of FN, primarily defined by the chemotherapy regimen. G-CSF administration is recommended when the incidence of FN is ≥20% or 10–20% with risk(s). However, the incidence of FN varies depending on the trial and design, and patient-specific risk factors for FN remain unclear. We previously performed a multicenter prospective cohort study in Japan, the CSPOR-BC FN study, evaluating the incidence of FN during perioperative chemotherapy for breast cancer. Herein, we conducted an additional analysis to explore thresholds of patient-specific risk factors for FN that could be evaluated before chemotherapy. We analyzed the risk factors for FN and verified the appropriateness of patient selection for prophylactic G-CSF administration. Methods: The previously reported CSPOR-BC FN study (PubMed ID=33631458) consecutively enrolled 1005 patients with stage I–III breast cancer between August 2015 and July 2017. In the current additional analysis, we intended to have 477 patients in the visiting group that evaluated true-FN, defined as ≥37.5℃ and grade 4 neutropenia. Multivariate analysis of risk factors for FN was performed, followed by the determination of cutoff values for age and pretreatment absolute neutrophil count (ANC) as risk factors. Results: Chemotherapy regimens administered were FEC (fluorouracil, epirubicin, and cyclophosphamide) in 170 patients (36%), E(A)C (epirubicin (doxorubicin) + cyclophosphamide) in 165 patients (35%), and TC (docetaxel + cyclophosphamide) in 142 patients (30%). The incidence of FN was 28.7% (N = 137). To evaluate the risk factors for FN, we predefined regimens, age, performance status (PS), stage, chemotherapy or radiotherapy history, infectious wounds, open wounds, ANC, and renal and liver dysfunction as potential risk factors. Multivariate analysis of risk factors for FN identified regimen (TC), age (≥65), low pretreatment ANC, treatment setting, and no primary pegfilgrastim prophylaxis as significant risk factors. Two patient-specific risk factors (age and pretreatment ANC) were analyzed. Logistic regression analysis revealed that age≥65 years was a significant risk factor (odds ratio=2.24, 95% confidence interval: 1.34–3.75). Applying a cutoff of 65 years (age) to predict FN, the sensitivity and specificity were 28.4 and 83.8%, respectively, which were inaccurate. Despite applying a cutoff of 67 years optimized from the receiver operating characteristic (ROC) curve, the sensitivity (22.4%), specificity (90.7%), and area under the curve (0.519) indicated low discrimination for predicting FN. The incidence of FN by age group was as follows: &amp;lt; 45 years, 30.8%; 45–55 years, 26.4%; 55–64 years, 20.9%; ≥65 years, 39.6%. Additionally, applying a cutoff of 2436/µL (pretreatment ANC) optimized from the ROC curve, the observed sensitivity (27.6%) and specificity (83.8%), and area under the curve (0.558) also indicated low discrimination for predicting FN. The incidence of FN by stratum of pretreatment ANC was as follows: &amp;lt; 2000, 33.3%; 2000–3000, 30.7%; 3000–4000, 29.9%; and &amp;gt;4000, 24.6. Accordingly, setting a cutoff value to predict FN incidence using age and/or pretreatment ANC was deemed inappropriate. Conclusion: Selecting patients for primary prophylactic G-CSF based on the existing FN risk can be challenging. Primary prophylactic G-CSF would be considered for every patient undergoing perioperative chemotherapy for breast cancer, especially Asians. ROC curve for FN and age. The AUC was 0.519. ROC curve for FN and neutrophil count. The AUC was 0.558. Citation Format: Kazutaka Narui, Takashi Ishikawa, Ikumi Takashima, Kosuke Kashiwabara, Yukari Uemura, Yuichiro Kikawa, Naruto Taira, Hirofumi Mukai. Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-12-06.

Abstract PO5-01-12: Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens

Abstract Late recurrence of breast cancer remains a significant challenge in patient management. Despite the established efficacy of hormone therapy, factors influencing late recurrence and the impact of different hormone therapy regimens on this outcome are not yet fully understood. This study aims to investigate the key determinants contributing to late recurrence within the context of different hormone therapy regimens. This study is a retrospective analysis of medical records from two institutions between 1988 and 2018, specifically examining patients who had HR-receptor positive breast cancer who underwent surgery and completed a 5-year course of standard hormone therapy. Primary endpoint is to identify the demographic, clinical and pathologic factors as associated with late recurrence. Out of 1929 eligible patients, 49.6% (956) received Tamoxifen (TMX), 37.6% (726) received Aromatase inhibitors (AI), and 12.8% (247) switched between regimens (TMX to AI or AI to TMX). Median follow-up was 12.1 years (3.75 - 21.41 years). During this period, all-type recurrence (ATR) occurred in 9.3% of all patients, with higher rates in the TMX recipients (12.2%). Locoregional and contralateral recurrence were identified in 10.6% of TMX recipients, 6.5% of patients who switched regimens, and 5% of AI recipients. In all patients, 5.4% were diagnosed with distant metastasis, with slightly higher rates in the TMX recipients (6.4%). Multiple sites in the bone, lung, liver and brain (34.3%) was the most prevalent location of distant metastasis (DM), followed by soft tissue (20%), liver (16.2%), bone (10.5%), lung (8.6%), and other locations. Significant differences in recurrence-free survival (RFS) were observed between hormone therapy groups (p=0.004, log-rank test). Mean overall RFS was 20.4 years (95% C.I. 20.1-20.9 years). TMX recipients had a mean RFS of 19.8 years, AI recipients had a mean RFS of 18.3 years and those who switched regimens had a mean RFS of 21.9 years. Further analysis showed premenopausal patients who switched regimens had higher RFS (p=0.014). No significant difference in RFS was seen between premenopausal patients receiving AI or Tamoxifen, or amongst post-menopausal patients with different hormone therapy regimens. No significant difference in distant metastasis-free survival (DMFS) was observed between hormone therapy groups (p=0.442). Mean overall DMFS was 21.5 years (95% C.I. 21.2 - 21.8 years), with TMX patients 21.1 years, AI patients at 18.6 years, and those who switched regimens at 21.4 years. Sub-analyses of DMFS in pre and postmenopausal patients with different hormone therapy regimens showed no significant differences. Multivariate analysis showed tumor size ≤ 2cm (p= 0.0001) and negative axillary node involvement (p= 0.0001) significantly decreased odds of developing late all-type recurrence (ATR) in TMX recipients. In patients who switched regimens, Her2 positivity (p=0.04) significantly decreased the odds of late ATR. In AI recipients, not undergoing axillary operation (p = 0.008) significantly increased the odds of late ATR. For TMX recipients, negative axillary node involvement (p=0.004), tumor size ≤ 2cm (p=0.03), and undergoing mastectomy (p=0.02) significantly decreased odds of distant metastasis (DM). Among patients who switched regimens, adjuvant anti-Her2 therapy (p=0.02) significantly decreased odds of DM. For AI recipients, high PR score (p=0.02) and undergoing sentinel lymph node biopsy significantly decreased odds of DM, while age &amp;lt; 50 years significantly increased odds of developing DM. These findings emphasize the significance of the relationship between hormone therapy regimens and factors affecting late recurrence, thereby providing valuable insights for clinical decision-making. Risk stratification based on identified factors can help in identifying patients at higher risk of late recurrence allowing for more intensive surveillance and potentially early intervention. Univariate (Chi-square, Logistic Regression) and Multivariate Analysis (Logistic Regression) for Clinicopathologic factors associated with all-type recurrence and distant metastasis after surgery and completion of 5-years endocrine therapy Table. a. LN lymph node b. SLNB, Sentinel lymph node biopsy c. ALND, Axillary lymph node dissection d. Cutoff values of Ki67 14% in KUAH and 10%in SNUH e. ER and PR cutoff value is 10% f. UV, Univariate analysis, MV multivariate analysis, O.R. Odds Ratio, C.I. Confidence Interval Citation Format: Mary Rose Mendoza, Eun-Shin Lee. Factors Influencing Late Recurrence in Breast Cancer: A Comprehensive Analysis of the Impact of Hormone Therapy Regimens [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-01-12.

Associations between pinch strength, cardiovascular events and all-cause mortality in patients undergoing maintenance hemodialysis

Background and aimsPatients undergoing maintenance hemodialysis (MHD) experience increased mortality and cardiovascular disease (CVD) risks; however, the potential connection between pinch strength (PS) and the prognosis of these patients remains unknown. Consequently, this study aimed to comprehensively assess the influence of PS and handgrip strength (HGS) on both survival and cardiovascular events (CVE) in patients undergoing MHD.MethodsData were gathered from patients undergoing MHD at the Hemodialysis Center of Guangzhou Red Cross Hospital in March 2021. We performed a retrospective follow-up spanning 24 months, with death serving as the primary endpoint for observation and CVE as the secondary endpoint. Multifactorial Cox regression analysis, Kaplan–Meier survival curves, trend tests, and restricted cubic spline were applied to explore the association.ResultsDuring a 24-month follow-up, data were collected from 140 patients undergoing MHD with an average age of 66.71 ± 12.61 years. Among them, 52 (37.14%) experienced mortality, whereas 36 (40.00%) had CVE without baseline CVD. Kaplan–Meier survival curves demonstrated better survival rates and reduced CVE risk for patients in the second, third, and fourth quartiles compared with those in the first quartile for PS. Adjusted analyses in different models revealed higher PS levels were independently associated with all-cause mortality (major model, model 4, HR, 0.78; 95% CI, 0.64–0.95) but not with CVE risk (unadjusted HR, 0.90; 95% CI, 0.77–1.05). Compared with lower quartile PS levels, higher PS levels significantly reduced all-cause mortality (HR, 0.31; 95% CI, 0.10–1.02), and this trend remained consistent (P for trend = 0.021). Finally, the restricted cubic spline method using different models showed a linear relationship between PS and all-cause mortality (P > 0.05), when PS exceeded 4.99 kg, the all-cause mortality of MHD patients significantly decreased.ConclusionsPS was independently associated with all-cause mortality but not with CVE in patients undergoing MHD.

Abstract PO3-02-08: Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China

Abstract Objective: The management of positive sentinel lymph node biopsies (SLNB) in patients with early-stage breast cancer remains a matter of controversy. Some studies have shown that not all breast cancer patients with positive sentinel lymph nodes (SLNs) benefit from further axillary lymph node dissection (ALND). Our study aims to analyse the risk factors and construct a new nomogram to predict non-sentinel lymph node (NSLN) metastasis in Chinese early-stage breast cancer patients with positive sentinel lymph nodes. Methods: The clinical data of 708 patients with early-stage breast cancer who attended The Fourth Hospital of Hebei Medical University for surgical treatment from January 2016 to December 2021 was retrospectively analyzed. All of them were female breast cancer patients with positive sentinel lymph nodes and underwent ALND. The patients were divided into modeling group and validation group according to the time of treatment. The patients in the modeling group were divided into a positive NSLN group and a negative NSLN group. The characteristics: age, maximum tumor diameter, the number of positive SLNs, proportion of positive SLNs, vessel carcinoma embolus, nerve invasion, status of ER, PR, HER-2 and Ki-67 were included in the analysis. And the independent risk factors of NSLN metastasis were screened by univariate (chi-square test) and multivariate (logistic regression) analysis. A nomogram model was established according to the screened independent risk factors, and the model was externally validated by the validation group. The ROC curve was plotted to calculate the area under the curve (AUC) and evaluate the predictive power of the nomogram model. A calibration curve and decision curve analysis (DCA) were used to evaluate the performance of the model. Results: Among the 708 patients, (modeling group n=410, validation group n=298), the average age, average number of positive SLNs, and NSLN positive rate were 50.9±11.1, 1.55±0.87 and 25.71%. The univariate analysis revealed statistically significant differences in the number of positive SLNs (P&amp;lt; 0.001), the proportion of positive SLNs (P &amp;lt; 0.001), vessel carcinoma embolus (P=0.001), nerve invasion (P=0.012), and ER status (P=0.029) in the NSLN-positive group compared with the negative group. The multifactorial logistic regression analysis revealed that the number of positive SLN (P=0.002; OR: 1.700; 95% CI: 1.219-2.370), the proportion of positive SLN (P=0.048; OR: 3.214; 95% CI: 1.001-10.490), vessel carcinoma embolus (P=0.010; OR: 2.076; 95% CI: 1.194-3.612), nerve invasion (P=0.024; OR: 2.119; 95% CI: 1.221-3.678), and ER status (P=0.045; OR: 2.978; 95% CI: 1.022-8.675) were independent risk factors for NSLN positivity. Furthermore, the nomogram was built using these 5 factors and validated on 298 patients in the validation group. The AUC was 0.728 (P&amp;lt; 0.001; 95%CI: 0.673-0.784) in the modeling group and 0.810 (P&amp;lt;0.001; 95%CI: 0.735-0.886) in the validation group. The calibration curves of the modeling and validation groups were close to the ideal curve, and DCA also showed that the model could be applied in clinical practice. Conclusion: For early-stage breast cancer with positive SLNs, these factors as the positive number of SLNs &amp;gt; 2, the ratio of positive SLNs &amp;gt; 50%, vessel carcinoma embolus, nerve invasion and ER-positive could predict NSLN metastasis well. The proposed nomogram appears to accurately estimate the likelihood of positive NSLNs and may greatly help the surgeon to decide intraoperatively whether to perform further ALND and avoid non-essential ALND as well as postoperative complications. Citation Format: Zhenchuan Song, Xueyi Zhao, Liu Yang. Risk factors and a new predictive nomogram for predicting the Non-sentinel Lymph Node Metastasis in 708 early-stage Breast Cancer Patients with Positive Sentinel Nodes in China [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-02-08.

Abstract PO1-27-03: Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary breast cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) has been increasingly used as the frontline therapy for the management of high-risk localized breast cancer (BC). Achieving pathological complete response (pCR) following NAC is associated with significantly better disease-free (DFS) and overall survival (OS), particularly for triple negative (TN) and HER2+ breast cancer. Among HER2 negative BC, HER2-low BC is a newly defined subset that has a HER2 immunohistochemical (IHC)-1+ or 2+/ISH negative phenotype. HER2 status is divided into 3 categories: HER2 positive, HER2-low, and HER2-zero. In this study, we investigated factors for pCR in relation to HER2 status and survival after NAC. Methods: A total of 197 cases with primary BC from January 2013 to July 2023 were enrolled in this study. There were 83 HER2 positive cases (including 7 HER2 2+/ISH+ cases) and 114 HER2 (78 HER2-low and 36 HER2-0) negative cases. HER2 3+ was dichotomized according to the staining cell rate (cut-off point; 90%) into the following two groups; HER2 3+/&amp;gt;90% (70 cases) and HER2 3+/&amp;lt; 90% (6 cases). The chemotherapy regimen was anthracycline and taxane with the addition of anti-HER2 therapy if the cases were HER2-positive. The clinicopathological factors examined were age, nodal status, tumor size, ER/PgR (cut-off points; 1% and 10%), and the Ki-67 index value (cut-off points: 20% and 40%). pCR was defined as the absence of residual invasive cancer on H&amp;E evaluation of the complete resected breast specimen (ypT0/Tis). We investigated the correlation between pCR and clinicopathological factors. The DFS and OS were calculated using the Kaplan-Meier method and analyzed using the log-rank procedure. Uni- and multivariate analyses of factors for pCR were performed using regression analysis. Results: 1. pCR was observed in 48 cases (57.8%) after NAC in the HER2 positive group and 17 cases (14.9%) in the HER2 negative group. 2. There was no significant relationship between the pCR rate and ER, PgR, Ki-67, menopausal and nodal status in the HER2 positive group. However, pCR was significantly observed more often in smaller tumors. HER2 3+( &amp;gt;90%) had a significantly higher pCR rate than HER2 3+(≤90%) and HER2 2+(ISH+). Multivariate analysis revealed that HER2 3+( &amp;gt;90%) and tumor size (≤5cm) were significant factors for pCR in HER2 positive BC cases. 3. Patients with pCR after NAC had significantly better DFS in HER2 positive BC cases. 4. There was a significant correlation between the pCR rate and ER≤10%, PgR≤10% and tumor size &amp;lt; 5cm in the HER2 negative BC cases. There was no relationship between the pCR rate and the HER2 status; 19.4% in HER2-0 and 12.8% in HER2-low. 5. Multivariate analysis revealed that the PgR status and tumor size were significant factors for pCR in the HER2 negative BC cases. 6. There was no significant difference in DFS between patients with pCR and non-pCR, especially in the luminal type BC cases. Moreover, no significant difference was observed between HER2-low and HER2-0. Conclusion: pCR rate after NAC was 57.8% in the HER2 positive cases and 14.9% in the HER2 negative cases. Moreover, the HER2 3+( &amp;gt;90%) group had a significantly higher pCR rate than the HER2 3+(≤90%) and HER2 2+(ISH+) groups. There was no correlation between the HER2 status (HER2-low and HER2-0) and pCR rate in the HER2 negative BC cases. In addition, the ER/PgR negativity (≤10%) was a significant factor for pCR in the HER2 negative cases. These findings suggest that the IHC data on the HER2 and ER/PgR status may be effective in predicting the pCR rate after NAC in BC cases. Citation Format: Nobuyuki Arima, Reiki Nishimura, Kazuhiro Muramoto, Atsushi Inayoshi, Tomio Tanigawa, Sugiko Watanabe. Studies on factors for pathological complete response after neoadjuvant chemotherapy in relation to HER2 status in primary breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-27-03.