Category: Statistics

Am J Cancer Res. 2024 Oct 15;14(10):4760-4771. doi: 10.62347/RIWX7204. eCollection 2024.

ABSTRACT

Nasopharyngeal carcinoma (NPC) is a malignant tumor that targets the nasopharyngeal mucosal epithelium. Concurrent chemoradiotherapy (CCRT) is a pivotal treatment modality for NPC, yet it poses a risk for osteoradionecrosis (ORN), a complication that can impede further treatment. This study sought to explore the risk factors for ORN in NPC patients post-CCRT and to construct predictive models. We performed a retrospective analysis of clinical data from 417 NPC patients treated with CCRT at the Affiliated Hospital of Jiangnan University, with 204 patients from Longyan First Hospital as a validation cohort for the models. Our findings indicated that a high radiation dose, tooth extraction after radiotherapy, inadequate oral hygiene, smoking, anemia, and advanced T staging were associated with an elevated risk of ORN in NPC patients following CCRT. We formulated risk prediction models for ORN utilizing a nomogram, gradient boosting machine (GBM), and random forest (RF) algorithms. The area under the curve (AUC) was 0.813 (95% CI: 0.724-0.902) for the nomogram model in the validation cohort, 0.821 (95% CI: 0.732-0.910) for the GBM, and 0.735 (95% CI: 0.614-0.855) for the RF. Delong’s test indicated no statistically significant differences in the AUC values among the three models. The nomogram has strong performance across both the training and validation cohorts, featuring a straightforward structure that is both intuitive and comprehensible. Taking into account the model’s discriminative power, generalizability, and clinical practicability, the nomogram was proven to be highly applicable in the current study.

PMID:39553231 | PMC:PMC11560816 | DOI:10.62347/RIWX7204

Am J Cancer Res. 2024 Oct 15;14(10):4880-4895. doi: 10.62347/YAWK6271. eCollection 2024.

ABSTRACT

The objective of this study was to identify characteristic factors for pathological complete response (pCR) in patients with locally advanced breast cancer (LABC) undergoing surgery and neoadjuvant chemotherapy (NACT). We retrospectively collected pathological data from 237 LABC patients treated in Affiliated Fuzhou First Hospital of Fujian Medical University from January 2010 to June 2021 and divided them into a training group (n = 166) and a validation group (n = 71) in a 7:3 ratio. A predictive model for pCR was established through logistic regression analysis and evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Significant differences between the pCR and non-pCR groups were observed in tumor size (P = 0.001), T stage (P = 0.003), estrogen receptor (ER) (P = 0.031), progesterone receptor (PR) (P = 0.013), human epidermal growth factor receptor 2 (HER-2) (P = 0.001), and molecular type (P = 0.001). The pCR group also had lower levels of carbohydrate antigen 19-9 (P = 0.013), cancer antigen 125 (P = 0.011), carcinoembryonic antigen (CEA) (P = 0.001), and systemic inflammatory index (SII) (P = 0.006), but a higher prognostic nutritional index (PNI) (P = 0.001) compared to the non-pCR group. There were no statistical differences in baseline data between the training and validation groups (P>0.05). Multivariate logistic regression analysis identified tumor size (P = 0.001), HER-2 (P = 0.010), CA125 (P = 0.005), CEA (P = 0.001), SII (P = 0.010), and PNI (P = 0.001) as independent risk factors for pCR. We constructed and visualized a nomogram model that included these 6 factors and developed a dynamic prediction model using the Dynamic Nomogram (DynNom) package. In a random sample of 6 patients, the probability of non-pCR reached 98.8%. The model’s AUC was 0.881 in the training group, with a clinical benefit rate of 71.68% and a concordance index (C-index) of 0.881, indicating a good fit. In the validation group, the AUC was 0.722, with a clinical benefit rate of 70.2% and a C-index of 0.722, also indicating a good fit. The Delong test showed a significant difference in AUC between the two groups (P = 0.027). In conclusion, this study constructed and validated a Nomogram model based on clinical pathological features and hematological indicators, finding that higher pCR rates were associated with smaller tumor size, HER-2 positivity, lower levels of CA125 and CEA, lower SII, and higher PNI, significantly enhancing breast cancer management and offering important clinical implications.

PMID:39553222 | PMC:PMC11560830 | DOI:10.62347/YAWK6271

Am J Cancer Res. 2024 Oct 15;14(10):4788-4802. doi: 10.62347/ZSWV1767. eCollection 2024.

ABSTRACT

Ovarian cancer is usually detected in the advanced stages. Existing treatments for high grade serous ovarian cancer (HGSOC) are not adequate and approximately fifty percent of patients succumb to this disease and die within five years after diagnosis. We conducted pre-clinical studies in a mouse model of ovarian cancer to evaluate disease outcome in response to treatment with the multi-kinase inhibitor cabozantinib. Cabozantinib is a receptor tyrosine kinase inhibitor with multiple targets including vascular endothelial growth factor receptor-2 (VEGFR-2), associated with immune suppression in ovarian cancer. Mice (C57BL/6) were injected with ID8-RFP ovarian tumor cells and treated with cabozantinib. Studies investigated ascites development, tumor burden and regulation of anti-tumor immunity with treatment. Mice treated with cabozantinib had significantly decreased solid tumor burden and decreased malignant ascites as compared to untreated controls. Improved outcome in cabozantinib treated mice was associated with a significantly higher percentage of CD69 early activated T cells, a higher percentage of granzyme B secreting CD8 T cells, the enhanced release of cytokines and chemokines known to recruit CD8 T cells and amplify T cell function, as well as reduced VEGFR-2. Findings suggest that cabozantinib is an important clinical agent capable of improving ovarian cancer in mice potentially in part by priming the autologous immune system to promote anti-tumor immunity.

PMID:39553221 | PMC:PMC11560812 | DOI:10.62347/ZSWV1767

Am J Cancer Res. 2024 Oct 15;14(10):4946-4955. doi: 10.62347/MHXS8480. eCollection 2024.

ABSTRACT

OBJECTIVE: To explore the value of preoperative prognostic nutritional index (PNI) and systemic immune inflammation index (SII) for predicting the efficacy and prognosis of patients with osteosarcoma undergoing neoadjuvant chemotherapy (NACT) combined with surgery.

METHODS: A retrospective study was conducted on patients with osteosarcoma undergoing NACT combined with surgery in Sun Yat-sen University Cancer Center from January 2017 to May 2019. The patients were grouped into a remission group (pCR group, 85 patients) and a non-remission group (non-pCR, 79 patients), according to the treatment efficacy. The pathological data as well as clinical data were collected from patients, which were subsequently employed for statistical analysis to determine the factors affecting the efficacy of the treatment. The diagnostic value of PNI and SII for predicting the efficacy were assessed through following up the patients for 5 years to observe their overall survival rate. COX regression analysis was leveraged to identify risk factors affecting the survival time. The impact of different PNI and SII levels on the survival time was observed.

RESULTS: Multivariate regression analysis showed that factors including Enneking stage, PNI level and SII level were in association with poor efficacy after NATC combined with surgery. The mortality within 5 years was higher and the 5-year overall survival rate was lower in the non-pCR group than those in the pCR group (both P < 0.05). The COX regression analysis indicated that PNI and SII levels were risk factors for poor prognosis in patients with osteosarcoma following NACT combined with surgery. Further analysis showed that patients with low PNI and high SII levels had a lower 5-year survival rate (P < 0.05).

CONCLUSION: Enneking stage, PNI, and SII levels were risk factors for poor efficacy in patients with osteosarcoma after NACT combined with surgery. Patients whose PNI level was low and SII level was high presented poor prognosis following the treatment.

PMID:39553218 | PMC:PMC11560818 | DOI:10.62347/MHXS8480

Am J Cancer Res. 2024 Oct 15;14(10):4803-4816. doi: 10.62347/MWLI5585. eCollection 2024.

ABSTRACT

OBJECTIVE: To evaluate the potential of leukocyte-specific protein 1 (LCP1) and adenosine diphosphate-dependent glucokinase (ADPGK) as predictive biomarkers for immunotherapy-related adverse events in late-stage non-small cell lung cancer (NSCLC) patients with the KARS G12C mutation undergoing treatment with programmed cell death protein-1 (PD-1) monoclonal antibodies.

METHODS: A total of 160 late-stage NSCLC patients with the KARS G12C mutation receiving PD-1 monoclonal antibody treatment were retrospectively analyzed. LCP1 and ADPGK expression levels were assessed at both mRNA and protein levels using validated methods. Statistical analyses, including correlation analysis, logistic regression, and receiver operating characteristic (ROC) curve analysis, were conducted to explore the association between LCP1 and ADPGK expression levels and the occurrence of immunotherapy-related adverse events.

RESULTS: The mRNA levels of LCP1 (2.43 ± 0.72 vs. 2.14 ± 0.67, t=2.311, P=0.023) and ADPGK (2.31 ± 0.61 vs. 1.98 ± 0.59, t=3.145, P=0.002) were significantly elevated in patients with adverse reactions. Similarly, protein levels of LCP1 (1.22 ± 0.28 vs. 1.07 ± 0.25, t=3.179, P=0.002) and ADPGK (1.01 ± 0.18 vs. 0.93 ± 0.19, t=2.488, P=0.015) were higher in this group. Correlation and logistic regression analyses revealed positive correlations between LCP1 and ADPGK mRNA levels and adverse event occurrence (LCP1: rho=0.186, P=0.019, OR=1.842; ADPGK: rho=0.246, P=0.002, OR=2.549). Protein levels of LCP1 and ADPGK also correlated with immunotherapy-related adverse events (LCP1: rho=0.254, P=0.001, OR=9.554; ADPGK: rho=0.19, P=0.016, OR=10.058). The combined assessment of LCP1 and ADPGK expression showed strong predictive power for identifying patients at increased risk of adverse events during PD-1 treatment (AUC=0.808), with the validation group achieving an AUC of 0.751.

CONCLUSION: LCP1 and ADPGK are potential independent predictive biomarkers for immunotherapy-related adverse events in late-stage NSCLC patients with the KARS G12C mutation. Their combined assessment may offer a valuable tool for risk stratification during PD-1 monoclonal antibody treatment.

PMID:39553202 | PMC:PMC11560835 | DOI:10.62347/MWLI5585

Front Vet Sci. 2024 Nov 1;11:1443847. doi: 10.3389/fvets.2024.1443847. eCollection 2024.

ABSTRACT

BACKGROUND: Myxomatous mitral valve disease (MMVD) is a common, acquired, and progressive canine heart disease. The presence of heart murmur and current cardiac biomarkers are useful in MMVD cases but are not sufficiently discriminatory for staging an individual patient.

OBJECTIVES: This study aimed to conduct a preliminary assessment of canine serum and plasma expression profiles of 15 selected miRNA markers for accurate discrimination between MMVD patients and healthy controls. Additionally, we aim to evaluate the effectiveness of this method in differentiating between pre-clinical (stage B1/B2) and clinical (stage C/D) MMVD patients.

ANIMALS: Client-owned dogs (n = 123) were recruited for the study. Following sample exclusions (n = 26), healthy controls (n = 50) and MMVD cases (n = 47) were analyzed.

METHODS: A multicenter, cross-sectional, prospective investigation was conducted. MicroRNA expression profiles were compared among dogs, and these profiles were used as input for predictive modeling. This approach aimed to distinguish between healthy controls and MMVD patients, as well as to achieve a more fine-grained differentiation between pre-clinical and clinical MMVD patients.

RESULTS: Performance metrics revealed a compelling ability of the method to differentiate healthy controls from dogs with MMVD (sensitivity 0.85; specificity 0.82; and accuracy 0.83). For the discrimination between the pre-clinical (n = 29) and clinical (n = 18) MMVD cases, the results were promising (sensitivity 0.61; specificity 0.79; and accuracy 0.73).

CONCLUSION AND CLINICAL IMPORTANCE: The use of miRNA expression profiles in combination with customized probabilistic predictive modeling shows good scope to devise a reliable diagnostic tool to distinguish healthy controls from MMVD cases (stages B1 to D). Investigation into the ability to discriminate between the pre-clinical and clinical MMVD cases using the same method yielded promising early results, which could be further enhanced with data from an increased study population.

PMID:39553198 | PMC:PMC11565599 | DOI:10.3389/fvets.2024.1443847

Obstet Med. 2024 Sep 17:1753495X241275847. doi: 10.1177/1753495X241275847. Online ahead of print.

ABSTRACT

BACKGROUND: Preeclampsia is an independent risk factor for vascular diseases. The Postpartum Preeclampsia Clinic (PPPC) intervenes in the first year postpartum to address these risks. This study aims to characterize physicians’ understanding and management of the cardiovascular risk associated with preeclampsia and whether this differs in physicians who had a patient attend the PPPC.

METHODS: Family physicians, obstetricians, internists, obstetric internists, and cardiologists in Edmonton were anonymously surveyed. Results were analyzed using SPSS.

RESULTS: Sixty-four surveys were returned, with physicians correctly identifying preeclampsia as a vascular risk factor 73% of the time. Physicians who had a patient attend the PPPC were more likely to counsel patients on their increased cardiovascular risk, although increased knowledge did not reach statistical significance.

CONCLUSION: Vascular risk reduction clinics may benefit the long-term management of patients with a history of preeclampsia by improving counseling by physicians, which may reduce the disproportionate vascular morbidity these patients face.

PMID:39553184 | PMC:PMC11563521 | DOI:10.1177/1753495X241275847

Obstet Med. 2024 May 23:1753495X241255812. doi: 10.1177/1753495X241255812. Online ahead of print.

ABSTRACT

OBJECTIVE: This study evaluates obstacles peripartum patients with additional medical needs face and services that would be helpful in obtaining this care.

STUDY DESIGN: A survey was administered to 226 patients at a clinic specializing in internal medicine care for peripartum patients. Data was analyzed through descriptive statistics and linear regression.

RESULTS: The three most reported barriers that interfered with attending medical appointments included the inability to leave work (41%), being too busy (33%), and lack of childcare (29%). Hispanic and Black patients reported more barriers to care as compared to White patients. The three most reported interventions that would be helpful in attending appointments were more virtual appointment options (38%), increased insurance coverage (31%), and provision of childcare (30%). Interventions were widely rated as helpful regardless of barriers faced and race reported.

CONCLUSIONS: Targeted interventions are needed to enhance access to peripartum care, especially for patients from marginalized racial and ethnic populations.

PMID:39553181 | PMC:PMC11563510 | DOI:10.1177/1753495X241255812

Obstet Med. 2024 Jul 25:1753495X241263135. doi: 10.1177/1753495X241263135. Online ahead of print.

ABSTRACT

BACKGROUND: Transthoracic echocardiography, a validated tool for risk assessment in non-pregnant population with sickle cell disease (SCD), uses tricuspid regurgitant velocity (TRV) over 2.5 m/s is an independent mortality risk factor. Its applicability in obstetrics lacks sufficient evidence.

METHODS: In this multicenter retrospective cohort study across five tertiary centers, we aimed to validate TRV as a determinant of increased maternal and fetal risk. Data was collected on 93 women and included 21 patients with TRV of at least 2.5 m/s. The maternal primary composite outcome included occurrence of vaso-occlusive crisis, acute chest syndrome, gestational hypertension, preeclampsia, and mortality. The fetal primary composite outcome comprised perinatal mortality, premature delivery, reduced birth weight, and fetal distress.

RESULTS: Adverse maternal and fetal events arose in both groups with no statistical difference.

CONCLUSION: This study cannot support TRV of 2.5 m/s or more as an independent predictor of adverse obstetric outcomes among women with SCD.

PMID:39553170 | PMC:PMC11563517 | DOI:10.1177/1753495X241263135

Cureus. 2024 Oct 16;16(10):e71587. doi: 10.7759/cureus.71587. eCollection 2024 Oct.

ABSTRACT

Background Currently, there is no known correlation between relevant parameters of respective non-adjacent spinal segments, which suggests the possibility of a third external factor. To our knowledge, no study has examined the humeral head position in consideration of spinal sagittal alignment.This study aims to establish new parameters related to the humeral head axis and evaluate the relationship between the axis of the humeral head and spinal sagittal alignment in asymptomatic volunteers. Methods Standing posteroanterior and lateral radiographs of the entire spine were obtained from 62 asymptomatic volunteers. We analyzed the relationship of the newly established parameters related to the humeral head axis We analyzed the relationship of the newly established parameters related to the humeral head axis and other established spinal parameters. The new parameters are: shoulder tilt (ST: the angle between a line drawn from the center of the humeral head to the center of the superior endplate of T1 and vertical line through the center of the humeral head), shoulder incidence (SI: the angle between a line perpendicular to the upper endplate of the T1 vertebra and a line joining the center of the upper endplate of the T1 vertebra and the axis of the humeral head), shoulder pelvic angle (SPA: the angle between a line joining the axis of the humeral head and the femoral head and a line joining the axis of the femoral heads and the center of the upper endplate of the S1 vertebra), C2 shoulder angle (C2SA: the angle between a line joining the C2 body center and the axis of the humeral head and a line joining the axis of the humeral head and the center of the upper endplate of the T1 vertebra). Statistical analysis was performed using Pearson’s correlation coefficient. Results Mean ST, SI, SPA, and C2SA were 20.0±20.6°, 43.7±21.6°, 7.7±6.6°, and 17.8±13.5° respectively. The SI was found to be correlated with pelvic tilt (r=0.373), lumbar lordosis (r=0.351), and thoracic kyphosis (r=0.469). Pelvic incidence was correlated with SPA (r=0.724), T1 pelvic angle (r=0.691), and C2 pelvic angle (r=0.667). Correlations were observed between SPA and T1PA (r=0.955) and C2PA (r=0.956), and between TIPA and C2PA (r=0.985). Conclusions This report introduced novel parameters related to humeral head position and confirmed their correlation with sagittal alignment from the cervical spine to the pelvis. Humeral head position may play a role in maintaining spinal sagittal balance.

PMID:39553153 | PMC:PMC11565215 | DOI:10.7759/cureus.71587