Cox Proportional Hazards Model Analysis Research Articles

Analysis of clinical characteristics and prognostic factors of elderly patients with renal cell carcinoma based on the SEER database.

To study the difference of clinical characteristics and prognostic factors from elderly patients with renal cell carcinoma (RCC), the statistical analysis was carried out based on the surveillance, epidemiology, and end results database. The relevant clinical information of 19,472 RCC patients from 2010 to 2015 were collected, and the differences of clinicopathological characteristics and survival rate was analyzed by log-rank method and Chi square test, respectively. Multivariate Cox regression model was used to explore the independent risk factors affecting the long-term survival of RCC patients. Results showed that the proportion of elderly RCC patients in the 60-64-year group in 2010 was 15.20%, but the value elevated to 18.51% in 2015, and the Chi-square test revealed the significant correlation between elderly RCC patients with gender, race, American Joint Committee on cancer stage, T stage, N stage, and M stage. The difference of survival time between the 60-69 year, 70-79 year, 80-84 year, and 85+ year group was significant, and Kaplan-Meier analysis showed a negative effects of age on survival rate of RCC patients, indicating a worsening trend with increasing age. Cox proportional hazards model analysis further confirmed that age was the important independent prognostic factor. Our study reveals that the onset age of RCC in elderly population is gradually decreasing, and the malignant degree of elderly RCC patients is increasing with age. The female elderly population could be more susceptible to RCC than male elderly population, and 85+ year population could also be cancer susceptible with a higher lymph node metastasis rate, later tumor stage, and poor prognosis, suggesting that these elderly populations should pay more attention to the RCC screening.

#3781 INSULIN RESISTANCE IS ASSOCIATED WITH INCIDENT CHRONIC KIDNEY DISEASE IN POPULATION WITH NORMAL RENAL FUNCTION

Abstract Background and Aims Insulin resistance is prevalent in chronic kidney disease (CKD) and may accelerate its progression. This study aimed to investigate whether insulin resistance was associated with the development of incident CKD in a population with normal renal function. Method A total of 3,331 individuals with normal renal function from a community-based cohort formed the study population. We determined the relationship between insulin resistance indices and incident CKD using Cox proportional hazard model and Kaplan-Meier survival analysis. Results During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 414 (12.4%) participants. The high homeostasis model assessment-insulin resistance (HOMA-IR) level group had an increased risk of incident CKD (HR, 1.40; 95% CI, 1.13-1.74; p = 0.002) compared to the normal group after adjusting for confounding factors The risk of incident CKD also increased with lower quantitative insulin sensitivity check index (QUICKI) levels (HR, 0.62; 95% CI, 0.41-0.92; p = 0.018) and higher leptin-adiponectin ratio (LAR) levels (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006). Conclusion Higher insulin resistance indices were associated with the incidence of CKD. Our data suggests that increased insulin resistance may be involved in the development of incident CKD in individuals with normal renal function.

A single baseline amyloid PET could be sufficient for predicting Alzheimer’s disease conversion in mild cognitive impairment

AbstractBackgroundBaseline amyloid burden in mild cognitive impairment (MCI) has been linked to conversion to Alzheimer’s disease (AD), but the comparison of baseline and longitudinal changes in amyloid burden for predicting AD remains unresolved. The objectives of this study aimed to compare the prognostic ability of baseline and longitudinal changes in amyloid burden in MCI patients.MethodSeventy‐five individuals with MCI were recruited and examined annually by clinical interviews for a mean follow‐up of 24 months (Range 11.6 – 42.0). [18F]Florbetaben positron emission tomography (PET) scans were performed. T1‐weighted 3D volumes were acquired for co‐registration, and to define regions of interest (ROIs). We examined whether baseline and longitudinal amyloid burden changes can improve AD conversion by Cox proportional hazard model analysis and receiver operating characteristic (ROC) curve analysis.ResultCox proportional hazards model analysis showed that baseline amyloid burden was significantly associated with increased risk of conversion to AD (hazard ratio [HR] = 10.0; 95% confidence interval [CI], 1.15 – 85.39; p = 0.04), but longitudinal amyloid burden changes was not (HR = 0.2; 95% CI, 0.04 – 1.51; p = 0.13). When predicting AD, longitudinal amyloid burden changes had better ROC accuracy of 65.2% (95% CI, 48.4 – 82.0%) than baseline amyloid burden of 59.6% (95% CI, 40.3 – 79.0%), without statistical significance in pairwise comparison.ConclusionA single baseline amyloid PET could be sufficient in the prediction of AD conversion in MCI.

Pancreatic cancer associated ascites: Risk factors, outcomes, and management.

e16305 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with significant morbidity and mortality as most patients present with advanced disease. The development of ascites has been associated with poor outcomes and further characterization and contemporary management strategies are needed. Therefore, we performed a comprehensive analysis of PDAC patients with ascites, including clinical and biological data, to describe its incidence, associated clinical factors, and outcomes. Methods: Patients were prospectively consented and enrolled the Gastrointestinal Biobank (“GI-Bank”) at Cedars-Sinai Medical Center, which collected patient specimens, associated clinical data, and self-reported questionnaires. Data was consolidated using a standard software tool (Redcap). Statistical analysis was conducted using Excel and using Datatab.net software tools. Results: Of the 437 patients with PDAC, 182 (41.6%) developed ascites. Overall survival (OS) between ascites and non-ascites groups were significantly different by log-rank test (p = 0.001), and estimated median OS was 473 days (95% CI [407, 537]) in ascites patients versus 554 days [467, 678] in non-ascites patients. In Cox proportional hazards model analysis, ascites status, but not sex or race, was associated with decreased survival (HR 1.49, [1.18, 1.87]). Ascitic fluid data was obtained in 77 patients; 62 (80.5%) had SAAG > 1.1; 14(22.6%) of SAAG > 1.1 patients also had positive cytology. The estimated median OS from the diagnosis of ascites was 100 days [76, 128] and median time to puncture was 4 days. Estimated median time from first tap to death was 56 days [42, 95]. 90 (49.5%) were treated with diuretics and 41 (22.5%) were treated with PleurX catheter. Patients with ascites had a worse survival and were more likely to receive greater than one chemotherapy regimen. There was no relationship between ascites and receipt of surgery or radiation. Conclusions: The development of ascites in patients with pancreatic cancer is common and contributes to significant morbidity and mortality. The use of diuretics is lower than would be expected for patients with elevated SAAG. Prospective evaluation of management strategies is needed to improve this important clinical conundrum.

Sarcopenia vs body mass index (BMI) as a prognostic biomarker in patients with metastatic clear cell renal cell carcinoma (mCCRCC) in the era of first line immune checkpoint inhibitors (ICIs).

e16515 Background: ICIs are an important systemic treatment option for patients with mCCRCC. Sarcopenia, defined as low muscle mass, is associated with inferior outcomes in mCCRCC. However, there is limited data regarding sarcopenia and overall survival (OS) in patients receiving treatment with ICI-based regimens. Our objective was to evaluate associations between sarcopenia and BMI with OS in patients with mCCRCC receiving first line ICIs. Methods: A retrospective review of patients with mCCRCC receiving first line ICI-based therapy at Fred Hutchinson Cancer Center between 1/2015 to 4/2022 was performed. Patients without CT scans within 75 days of treatment initiation were excluded. Skeletal muscle index (SMI) at the level of L3 was measured using validated techniques. Sarcopenia was classified according to an international definition (SMI < 55 cm2/m2 for men and SMI < 39 cm2/m2 for women). BMI was defined as underweight ( < 19 kg/m2), normal (19-24.99kg/m2), overweight (25-29.99 kg/m2), and obese ( > 30 kg/m2). OS was estimated using the Kaplan-Meier method. Associations with OS were evaluated with Cox proportional hazard model analysis. Results: A total of 96 patients (25% female) with a median age of 62 (Interquartile range, IQR 55-68), met inclusion criteria. Due to missing CT images, 9 (9%) patients were excluded. 10 (11%), 43 (49%), and 22 (25%) were International Metastatic RCC Database Consortium (IMDC) favorable, intermediate, and poor risk respectively (12 unknown). Median follow up was 23 months (IQR 12-35). First-line therapy included ICI monotherapy (N = 15), ipilimumab/nivolumab (N = 49) or ICI/VEGF targeted therapy (N = 23). In total, 43 (49%) patients were sarcopenic. Median OS overall was 42.6 months (IQR 15.9-NR). Two-year OS was 57% in sarcopenic vs 76% in non-sarcopenic patients (Log-Rank p = 0.06). On multivariable analysis adjusted for IMDC risk criteria, age, and gender, SMI (continuous) was independently associated with survival (HR 0.94, 95%CI 0.90-0.99, p = 0.03) while BMI was not significantly associated with OS on univariate or multivariable analyses (p > 0.05). Among the 49 patients receiving ipilimumab/nivolumab combination therapy, sarcopenia was significantly associated with decreased 2-year OS (47% vs. 77%, p = 0.02). Across IMDC risk strata, sarcopenia was significantly associated with decreased 2-year OS in the intermediate risk group only (44% vs. 83%, p = 0.01). Conclusions: Sarcopenia, but not BMI, is independently associated with OS among patients with mCCRCC receiving first line ICI-based regimens. This finding is consistent with the literature suggesting that muscle mass measurement provides an important prognostic biomarker for patients with mCCRCC. SMI could inform treatment selection and adoption of muscle measures when risk-stratifying this population should be considered.

MSR92 Racial and Smoking Status Disparities in Mediation Effects on Liraglutide-Associated Cardiovascular Outcomes: A Dynamic Path Analysis Using Leader Trial Data

Mediation analyses are useful to disentangle possible causal pathways from an exposure/treatment to its clinically relevant outcomes. Mediation effects are commonly presented in changes in hazard ratios obtained from Cox proportional hazard model analyses, yet the assumption of proportionality is however violated with a post-exposure mediator added into the analysis. Dynamic path analysis evolved more recently where the proportionality is not required and all time-varying mediators can be simultaneously modeled, thereby reflecting the complexity of mediators in causal pathways. We sought to apply dynamic path analyses for assessing the heterogeneity of mediation effects on liraglutide-associated major adverse cardiovascular event (MACE) outcome by racial and smoking status of patients.

The timing of statin initiation on survival outcomes of cancer patients treated with immune checkpoint inhibitors: A retrospective cohort study.

e14672 Background: Concomitant use of statins has been associated with improved survival outcomes in patients treated with immune checkpoint inhibitors (ICIs), but it is unclear if the timing of statin initiation plays a role in patient outcomes. We aimed to investigate the outcomes of patients who were started on a statin before and after initiation of ICI therapy. Methods: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. We collected data on statin use including the timing of statin initiation, basic demographics, underlying comorbidities, and cancer information. We compared the overall survival (OS) and progression-free survival (PFS) between statin and non-statin users using Cox proportional hazard model analysis and Kaplan-Meier Survival analysis. Results: Among 734 patients who received ICIs, 76 patients received statins after ICI initiation, 52 patients received statins before ICI initiation, and 606 were non-statin users. Patients who received statins after ICI had a longer OS (median 37.6 vs. 11.3 vs. 10.3 months, p = 0.01) and PFS (median 10.5 vs. 5.6 vs. 6.3 months, p = 0.02) than patients who received statins before ICI and non-statin users. In Cox proportional hazard analyses, the use of statins after ICI was associated with a lower risk of mortality (HR, 0.65 [95% CI: 0.45-0.94], p = 0.02) or disease progression (HR, 0.71 [95% CI: 0.53-0.95], p = 0.02) compared with non-statin users. On the other hand, the use of statins before ICI was not associated with a lower risk of mortality (HR, 1.46 [95% CI: 0.96-2.22], p = 0.08) or disease progression (HR, 1.22 [95% CI: 0.86-1.73], p = 0.26) compared with non-statin users. These trends were observed in multivariate Cox proportional analyses adjusting for underlying comorbidities, cancer stage, type, and therapy. Conclusions: The use of statins after the initiation of immunotherapy is associated with improved survival outcomes. [Table: see text]

Augmented curation of disease diagnoses and medications for patients with hepatocellular carcinoma.

e13573 Background: Unstructured EHR data contains nuanced rich insights for Real World Evidence (RWE) studies, however harnessing this unstructured data at scale can be challenging. Here, we evaluated two Natural Language Processing-based curation (“augmented curation”) models to identify medical conditions and medications from clinical notes for patients with hepatocellular carcinoma at City of Hope National Medical Center. Methods: We deployed two augmented curation models originally trained on de-identified EHR data from the nference nSights platform, a federated data platform comprising clinical data from several Academic Medical Centers, on clinical notes found in the City of Hope POSEIDON platform, an oncology insights engine. We assessed their performances using manual chart review as reference. We then calculated an Enrichment Factor (EF) score for augmented curation model extraction and its 95% confidence intervals. The EF score was defined as the number of patients captured by either augmented curation or structured data divided by the number of patients captured by structured data alone. Results: The augmented curation models captured conditions and medications from clinical notes with F1 scores of 0.93 and 0.95, respectively. Compared to structured EHR data alone, the disease diagnosis model captured significantly more individuals with signs and symptoms such as vomiting (EF: 22.8, 95% CI: [15.2, 41.1]), weight loss (EF: 5.0, 95% CI: [4.1, 6.6]), nausea (EF: 4.3, 95% CI: [3.1, 6.9]), and edema (EF: 3.1, 95% CI: [2.7, 3.7]). Similarly, the medication use augmented curation model captured significantly more individuals with medications such as interferon, aspirin, and pembrolizumab. From a Cox proportional hazards model analysis, we found that a survival model using augmented curation-based features and structured data achieved a model concordance of 0.745 (95% CI: [0.741, 0.748]), compared to 0.722 (95% CI: [0.717, 0.726]) for the model based on structured data alone. In addition, the augmented curation-based survival model identified jaundice (HR: 2.0, 95% CI: [1.5, 2.7]) as a significant risk factor for mortality, which was not picked up by the structured data-based survival model. Conclusions: Overall, this study shows that augmented curation models can be used to accurately capture comorbidities and medications from unstructured clinical notes, and these extracted covariates are correlated with clinically meaningful endpoints such as survival. We recommend using augmented curation as a standard insight generation approach in RWE study protocols.

Effect of obstructive sleep apnea on prognosis in patients with acute coronary syndromes with varying numbers of standard modifiable risk factors: insight from the OSA-ACS study

BackgroundStandard modifiable risk factors (SMuRFs) increase the risk of cardiovascular events in patients with acute coronary syndrome (ACS) and are also strongly associated with obstructive sleep apnea (OSA) in a bidirectional relationship. However, the association of OSA with recurrent cardiovascular events in ACS patients based on the number of SMuRFs remains unclear. Hence, we aimed to elucidate the prognostic implication of OSA in ACS patients stratified by the number of SMuRFs.MethodsThis was a post hoc analysis of the OSA-ACS study (NCT03362385), including 1927 patients admitted for ACS and undergoing portable sleep monitoring. OSA was defined as an apnea hypopnea index ≥ 15 events/h. The primary endpoint was major adverse cardiovascular and cerebrovascular event (MACCE) including cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina or heart failure, and ischemia-driven revascularization. Cox proportional hazards model and Kaplan-Meier analysis were used to investigated the relationship between OSA and subsequent cardiovascular events after patients were stratified by the number of SMuRFs.ResultsAmong 1927 patients enrolled, 130 (6.7%) had no SMuRF, 1264 (65.6%) exhibited 1–2 SMuRFs and 533 (27.7%) presented 3–4 SMuRFs. With the increase of the number of SMuRFs, the proportion of OSA in ACS patients tended to increase (47.7% vs. 51.5% vs. 56.6%), but there was no significant difference between them (P = 0.08). After the stratification of ACS patients via SMuRF numbers and adjustment for confounding factors, fully adjusted Cox regression indicated that OSA increased the risk of MACCE (adjusted HR, 1.65; 95%CI, 1.06–2.57; P = 0.026) and ischemia-driven revascularization (adjusted HR, 2.18; 95%CI, 1.03–4.65; P = 0.042) in ACS patients with 3–4 SMuRFs.ConclusionsIn hospitalized ACS patients, OSA is associated with an increased risk of MACCE and ischemia-driven revascularization among patients with 3–4 SMuRFs. Therefore, screening for OSA should be emphasized in ACS patients with 3–4 SMuRFs, and intervention trials should be prioritized in these high-risk patients.

Sarcopenia Is a Prognostic Factor in Patients Undergoing Percutaneous Endoscopic Gastrostomy.

(1) Background: Percutaneous endoscopic gastrostomy (PEG) is a widely used long-term enteral nutrition method, but little is known about the associated prognostic factors in patients with PEG. Sarcopenia, a condition characterized by a loss of skeletal muscle mass, increases the risk of developing various gastrointestinal disorders. Yet, the relationship between sarcopenia and the prognosis after PEG remains unclear. (2) Methods: We conducted a retrospective study of patients who underwent PEG consecutively from March 2008 to April 2020. We analyzed preoperative sarcopenia and the prognosis of patients after PEG. We defined sarcopenia as a skeletal muscle index at the level of the third lumbar vertebra of ≤29.6 cm2/m2 for women and ≤36.2 cm2/m2 for men. Cross-sectional computed tomography images of skeletal muscle at the level of the third lumbar vertebra were evaluated using DICOM image analysis software (OsiriX). The primary outcome was the difference in overall survival after PEG based on the status of sarcopenia. We also performed a covariate balancing propensity score matching analysis. (3) Results: Of 127 patients (99 men, 28 women), 71 (56%) were diagnosed with sarcopenia, and 64 patients died during the observation period. The median follow-up period did not differ between patients with and without sarcopenia (p = 0.5). The median survival time after PEG was 273 days in patients with sarcopenia and 1133 days in those without (p < 0.001). Cox proportional hazard model analyses identified three factors that were significantly associated with overall survival: sarcopenia (adjusted hazard ratio [HR]: 2.9, 95% confidence interval [CI]: 1.6-5.4, p < 0.001), serum albumin level (adjusted HR: 0.34, 95% CI: 0.21-0.55, p < 0.001) and male sex (adjusted HR: 2.0, 95% CI: 1.1-3.7, p = 0.03). Propensity score-matched analysis (n = 37 vs. 37) showed that the survival rate was lower in the sarcopenia group than in the non-sarcopenia group (at 90 days: 77% (95% CI, 59-88) vs. 92% (76-97), at 180 days: 56% (38-71) vs. 92% (76-97), and at one year: 35% (19-51) vs. 81% (63-91), p = 0.0014). (4) Conclusions: Sarcopenia was associated with poor prognosis in patients having undergone PEG.

Prognostic Value of Lymph Node Parameters in Elderly Patients With Stage III Serous Ovarian Cancer Based on Competing Risk Model.

Competing risk models were used in this study. The purpose of this study was to assess the predictive usefulness of lymph node characteristics in elderly patients with stage III serous ovarian cancer. We conducted a retrospective analysis on 148,598 patients from 2010 to 2016 using the surveillance, epidemiology, and end results database. Lymph node characteristics were collected and examined, including the number of lymph nodes retrieved the number of lymph nodes examined (ELN) and the number of positive lymph nodes (PN). Using competing risk models, we evaluated the connection between these variables and overall survival (OS) and disease-specific survival (DSS). This study included a total of 3457 ovarian cancer patients. Multivariate analysis using the COX proportional hazards model found that ELN>22 was an independent predictive factor for both OS (hazard ratio [HR] [95% CI]=0.688 [0.553 to 0.856], P <0.05) and DSS (HR [95% CI]=0.65 [0.512 to 0.826], P <0.001), PN>8 was identified as a significant risk factor for both OS (HR [95% CI]=0.908 [0.688 to 1.199], P =0.497) and DSS (HR [95% CI]=0.926 [0.684 to 1.254], P =0.62). Subsequently, using the competing risk model, ELN>22 was found to be an independent protective factor for DSS (HR [95% CI]=0.738 [0.574 to 0.949], P =0.018), while PN>8 was identified as a risk factor for DSS (HR [95% CI]=0.999 [0.731 to 1.366], P =1). Our findings demonstrate the robustness of the competing risk model to evaluate the results of the COX proportional hazards model analysis.

CTLA4 mRNA is downregulated by miR-155 in regulatory T cells, and reduced blood CTLA4 levels are associated with poor prognosis in metastatic melanoma patients.

Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint expressed in regulatory T (Treg) cells and activated T lymphocytes. Despite its potential as a treatment strategy for melanoma, CTLA-4 inhibition has limited efficacy. Using data from The Cancer Genome Atlas (TCGA) melanoma database and another dataset, we found that decreased CTLA4 mRNA was associated with a poorer prognosis in metastatic melanoma. To investigate further, we measured blood CTLA4 mRNA in 273 whole-blood samples from an Australian cohort and found that it was lower in metastatic melanoma than in healthy controls and associated with worse patient survival. We confirmed these findings using Cox proportional hazards model analysis and another cohort from the US. Fractionated blood analysis revealed that Treg cells were responsible for the downregulated CTLA4 in metastatic melanoma patients, which was confirmed by further analysis of published data showing downregulated CTLA-4 surface protein expression in Treg cells of metastatic melanoma compared to healthy donors. Mechanistically, we found that secretomes from human metastatic melanoma cells downregulate CTLA4 mRNA at the post-transcriptional level through miR-155 while upregulating FOXP3 expression in human Treg cells. Functionally, we demonstrated that CTLA4 expression inhibits the proliferation and suppressive function of human Treg cells. Finally, miR-155 was found to be upregulated in Treg cells from metastatic melanoma patients compared to healthy donors. Our study provides new insights into the underlying mechanisms of reduced CTLA4 expression observed in melanoma patients, demonstrating that post-transcriptional silencing of CTLA4 by miRNA-155 in Treg cells may play a critical role. Since CTLA-4 expression is downregulated in non-responder melanoma patients to anti-PD-1 immunotherapy, targeting miRNA-155 or other factors involved in regulating CTLA4 expression in Treg cells without affecting T cells could be a potential strategy to improve the efficacy of immunotherapy in melanoma. Further research is needed to understand the molecular mechanisms regulating CTLA4 expression in Treg cells and identify potential therapeutic targets for enhancing immune-based therapies.

PO-02-067 PREDICTORS AND IMPACT OF PULMONARY VEIN NON-RECONNECTION IN THE SECOND PROCEDURE AFTER ABLATION INDEX-GUIDED PULMONARY VEIN ISOLATION FOR ATRIAL FIBRILLATION

Reconnection of the pulmonary vein (PV) is the primary mechanism of atrial tachyarrhythmia (AT) recurrence after atrial fibrillation (AF) ablation. In patients with AT recurrence after the first ablation index (AI)-guided AF ablation, we examined the predictors of PV non-reconnection and its impact on the outcome after the second procedure. We aimed to elucidate the predictor of PV non-reconnection and its impact on the outcome after the second ablation procedure. Among the consecutive 2089 patients undergoing the first AI-guided AF ablation, we studied 289 with AT recurrence undergoing the second procedure. We compared clinical characteristics and outcomes between the patient groups with and without PV reconnection at the beginning of the second procedure. Of the 289 patients, 134 (46%) had non-reconnection, while the other 155 (54%) had reconnection at least in one PV. Patients' characteristics, including AF type (paroxysmal AF, 41% versus 48%; persistent AF, 28% versus 26%; long-standing persistent AF, 31% versus 26%, respectively, P=0.50), were similar between the two groups. The percentage of first-pass PV isolation (FPI) in both PV sides in the first ablation procedure was significantly higher in PV non-reconnection than in those with reconnection group (77% versus 43%, respectively, p<0.001). Multivariate logistic regression analysis revealed that FPI at the first procedure (odds ratio, 0.23 (95% confidence interval (CI), 0.13-0.38), p<0.001) was the only independent predictor of PV reconnection. After the second procedure, Kaplan-Meier analysis revealed that AT recurrence rate was significantly higher in patients with PV non-reconnection than in those with reconnection (Log-rank test, p=0.005). Multivariate Cox proportional hazard model analysis revealed that PV non-reconnection (hazard ratio (HR), 1.71 (95%CI, 1.14-2.55), p=0.008), left atrial dimension (1.04 (1.01-1.07), p=0.006), and left ventricular ejection fraction (0.98 (0.96-0.99), p=0.005) were independent predictors of AT recurrence. However, AF type was not: HR to paroxysmal AF (reference) was 1.10 (95%CI, 0.67-1.83) (p=0.70) in persistent AF and 1.30 (0.82-2.03) (p=0.26) in long-standing persistent AF. FPI in the first procedure was the only independent predictor of PV non-reconnection. After the second procedure, PV non-reconnection was an independent worsening predictor of AT recurrence, suggesting a need for an aggressive search for non-PV mechanisms.

Age-Specific Differences in the Risk of Colorectal Precursor Lesions Among Patients with Type 2 Diabetes Undergoing Surveillance Colonoscopy.

The incidence rate of colorectal cancer (CRC) in young adults is rising in parallel with type 2 diabetes (T2D). The majority of CRC develop through two main subtypes of precursor lesions; adenomas and serrated lesions. The associations between age and T2D on development of precursor lesions remain uncertain. We studied the association of T2D with the development of adenomas and serrated lesions in individuals <50 versus ≥50 years of age, in a population undergoing long-term regular surveillance colonoscopy due to an elevated risk of CRC. A case-control study was conducted on patients who were enrolled in a surveillance colonoscopy program between 2010-2020. Findings at colonoscopy, clinical and demographic features were collected. Adjusted and unadjusted binary logistic regression assessed the association of age, T2D, sex, and other medical conditions and lifestyle-related factors with different subtypes of precursor lesions diagnosed at colonoscopy. Cox proportional hazards model analysis determined the association of T2D and other confounders with development time for precursor lesions. Cases included 412 patients <50y [mean age 38.7 (range, 24-49y)] and 824 sex-matched controls ≥50y [62.1 (50-75y)]. Individuals <50y were less likely to have been diagnosed with T2D than those ≥50y (7% vs 22%, P-value<0.001). During the follow-up period, there was no significant association between T2D and diagnosis of any precursor lesions, but when considering development time, individuals with T2D developed non-significant adenomas earlier than those without T2D (HR =1.46; 95% CI: 1.14-1.87; P-value=0.003). However, this was not independent of age or findings at index colonoscopy. T2D does not further increase the incidence of adenomas or serrated lesions in either a young or older cohort undergoing long-term surveillance colonoscopy.

Usefulness of serum creatinine and cystatin C ratio as a screening tool for predicting prognosis in patients with pancreatic cancer.

This study aimed to evaluate the usefulness of the serum creatinine/cystatin C (Cr/CysC) ratio as a prognostic factor after pancreatic surgery in patients with pancreatic cancer. We retrospectively analyzed the data of 88 patients with pancreatic ductal carcinoma who underwent pancreatic surgery from January 2017 to December 2020. CysC measured from frozen serum samples and circulating Cr levels were used to calculate the Cr/CysC ratio. The cutoff value of the Cr/CysC ratio was determined using receiver operating characteristic curves. Cox proportional hazards model analysis and survival curves were applied to identify the prognostic factors. The optimal cutoff value of the Cr/CysC ratio for predicting mortality after surgery was 1.05. This study included 20 (22.7%) and 68 (77.3%) patients with high and low Cr/CysC ratios, respectively. The low Cr/CysC ratio was significantly associated with female sex (p=0.020) and higher levels of C-reactive protein (p=0.020). The postoperative length of stay was significantly longer in patients with low Cr/CysC rates (p=0.044). Patients with low Cr/CysC ratio showed poorer prognosis in relapse-free survival (hazard ratio [HR]=3.33; 95% confidence interval [CI]: 1.54-4.20; p=0.002) and overall survival (HR=2.52, 95% CI: 1.04-6.10, p=0.041), respectively, which were significantly worse than in those with high Cr/CysC ratios (p=0.003 and 0.049, respectively). The Cr/CysC ratio could be a useful screening tool for predicting the prognosis of patients with pancreatic ductal carcinoma undergoing pancreatic surgery.

Tuberculosis notifications in regional Victoria, Australia: Implications for public health care in a low incidence setting.

Regionality is often a significant factor in tuberculosis (TB) management and outcomes worldwide. A wide range of context-specific factors may influence these differences and change over time. We compared TB treatment in regional and metropolitan areas, considering demographic and temporal trends affecting TB diagnosis and outcomes. Retrospective analyses of data for patients notified with TB in Victoria, Australia, were conducted. The study outcomes were treatment delays and treatment outcomes. Multivariable Cox proportional hazard model analyses were performed to investigate the effect of regionality in the management of TB. Six hundred and eleven (7%) TB patients were notified in regional and 8,163 (93%) in metropolitan areas between 1995 and 2019. Of the 611 cases in the regional cohort, 401 (66%) were overseas-born. Fifty-one percent of the overseas-born patients in regional Victoria developed TB disease within five years of arrival in Australia. Four cases of multidrug-resistant tuberculosis were reported in regional areas, compared to 97 cases in metropolitan areas. A total of 3,238 patients notified from 2012 to 2019 were included in the survival analysis. The time follow-up for patient delay started at symptom onset date, and the event was the presentation to the healthcare centre. For healthcare system delay, follow-up time began at the presentation to the healthcare centre, and the event was commenced on TB treatment. Cases with extrapulmonary TB in regional areas have a non-significantly longer healthcare system delay than patients in metropolitan (median 64 days versus 54 days, AHR = 0.8, 95% CI 0.6-1.0, P = 0.094). Tuberculosis in regional Victoria is common among the overseas-born population, and patients with extrapulmonary TB in regional areas experienced a non-significant minor delay in treatment commencement with no apparent detriment to treatment outcomes. Improving access to LTBI management in regional areas may reduce the burden of TB.

Persistent or Recurrent Disease in Thyroid Cancer Survivors Who Have Elevated Serum Antithyroglobulin Antibodies

ObjectiveDetection of residual differentiated thyroid cancer is important but difficult. A variety of imaging modalities and biochemical markers has been used with moderately good success. We hypothesized that elevated perioperative serum antithyroglobulin antibody (TgAb) levels would also be a predictive marker for persistent or recurrent thyroid cancer. MethodsWe performed a retrospective analysis of 277 differentiated thyroid cancer survivors divided into 2 groups: (1) those with low or normal serum TgAb (TgAb−) and (2) those with elevated serum TgAb (TgAb+). All patients were seen at one major academic medical center. Patients were followed for a median of 7.54 years. ResultsPatients in the TgAb+ group were more likely to have positive lymph nodes at initial surgery, to be assigned to a higher American Joint Committee on Cancer stage, and to have significantly higher incidence of persistent/recurrent disease. The higher incidence of persistent/recurrent cancer was significant under univariable and multivariable (including TgAb status, age, and sex) Cox proportional hazards model analysis. ConclusionWe conclude that individuals with elevated serum TgAb at the outset should be followed with a higher index of suspicion for persistent/recurrent thyroid cancer.

Prognostic value of C-reactive protein to albumin ratio for mortality in acute kidney injury

BackgroundInflammation plays an important role in the development of acute kidney injury (AKI). However, there are few studies exploring the prognostic influence of C-reactive protein to albumin ratio (CAR) among AKI patients. In this study, we investigated whether CAR could be a useful marker to predict the mortality of AKI.MethodsA total of 358 AKI patients were extracted from the Medical Information Mart for Intensive Care III (MIMIC III) database. C-reactive protein (CRP) and albumin were measured at ICU admission. The clinical outcome was 365-day mortality. Cox proportional hazards model and Kaplan-Meier survival analysis were conducted to evaluate the association between CAR and outcome.ResultsCompared with patients in the survival group, nonsurvivors had higher CAR levels. The area under the receiver operating characteristic (ROC) curve of CAR was higher than that of CRP and albumin for mortality (0.64 vs. 0.63, 0.59, respectively). The cut-off point of CAR for mortality was 7.23. In Cox proportional-hazard regression analysis, CAR (hazards ratio (HR) =2.04, 95% confidence interval (CI) =1.47-2.85, p < 0.001 for higher CAR) and Simplified Acute Physiology Score II (HR = 1.02, 95%CI = 1.00-1.03, p = 0.004) were independent predictors of 365-day mortality.ConclusionsOur study demonstrated that a higher level of CAR was associated with 365-day mortality in AKI patients.

Transfer of passive immunity and survival in Jersey heifer calves fed heat-treated pooled colostrum.

Acquisition of adequate transfer of passive immunity (ATPI) by calves depends on the absorption of sufficient mass of colostral immunoglobulin G (IgG). Several studies report conflicting evidence regarding the ability of feeding pooled colostrum to achieve ATPI. Pooling colostrum is practical and efficient for some dairies, and recommendations are required to prevent failure of transfer of passive immunity (FTPI) in calves following pooling. This study aimed to determine the effect of pooling colostrum on serum IgG concentrations, FTPI, and preweaning mortality in calves. A prospective study was performed on two conventional Jersey dairy farms where heat treatment of colostrum occurred in the same colostrum processing kitchen. Four to 10 cows contributed to colostrum pools. A sample of the colostrum pool fed to the calves and serum from calves at 24-72 h was collected for IgG concentration determination by single radial immunodiffusion assay. Multivariable and logistic regression analyses were performed to evaluate factors that predicated serum IgG concentrations and the probability of FTPI, respectively. A Cox proportional hazard model analysis was performed to determine risk factors for mortality over the preweaning period. A total of 164 calves fed 28 colostrum pools were enrolled. Birth weight, number of colostrum feedings and pool IgG concentrations were significant predictors of calf serum IgG concentrations at 24-72 h, whereas the number of colostrum feedings and age at bleeding to determine passive transfer status were not significant predictors of calf serum IgG concentrations at 24-72 h. The prevalence of FTPI was 4.9%. Birth weight, pool IgG concentrations, number of colostrum feedings, and age at bleeding to check for passive transfer status were not significant predictors of the probability of FTPI at 24-72 h. The incidence of mortality was 4.3%. Passive transfer status was not a predictor of mortality. Our study demonstrates the effect of pooling colostrum on serum IgG concentrations even in herds where colostrum with higher median colostrum IgG concentrations is fed to calves. The results emphasize the recommendations to assess pooled colostrum IgG concentrations before feeding calves.

Diagnostic and Prognostic Roles of C-Reactive Protein, Procalcitonin, and Presepsin in Acute Kidney Injury Patients Initiating Continuous Renal Replacement Therapy

For reducing the high mortality rate of severe acute kidney injury (AKI) patients initiating continuous renal replacement therapy (CRRT), diagnosing sepsis and predicting prognosis are essential. However, with reduced renal function, biomarkers for diagnosing sepsis and predicting prognosis are unclear. This study aimed to assess whether C-reactive protein (CRP), procalcitonin, and presepsin could be used to diagnose sepsis and predict mortality in patients with impaired renal function initiating CRRT. This was a single-center, retrospective study involving 127 patients who initiated CRRT. Patients were divided into sepsis and non-sepsis groups according to the SEPSIS-3 criteria. Of the 127 patients, 90 were in the sepsis group and 37 were in the non-sepsis group. Cox regression analysis was performed to determine the association between the biomarkers (CRP, procalcitonin, and presepsin) and survival. CRP and procalcitonin were superior to presepsin for diagnosing sepsis. Presepsin was closely related to the estimated glomerular filtration rate (eGFR) (r = -0.251, p = 0.004). These biomarkers were also evaluated as prognostic markers. Procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher all-cause mortality using Kaplan-Meier curve analysis. (log-rank test p = 0.017 and p = 0.014, respectively). In addition, procalcitonin levels ≥3 ng/mL and CRP levels ≥31 mg/L were associated with higher mortality in univariate Cox proportional hazards model analysis. In conclusion, a higher lactic acid, sequential organ failure assessment score, eGFR, and a lower albumin level have prognostic value to predict mortality in patients with sepsis initiating CRRT. Moreover, among these biomarkers, procalcitonin and CRP are significant factors for predicting the survival of AKI patients with sepsis-initiating CRRT.