Multivariate Cox Proportional Hazards Analysis Research Articles

Metachronous primary gastric cancer after endoscopic resection in patients with esophageal squamous cell carcinoma.

This study aimed to evaluate the risk factors for developing metachronous primary Gastric Cancer (GC) after Endoscopic Resection (ER) for esophageal Squamous Cell Carcinoma (SCC). We studied 283 patients with esophageal SCC who underwent ER. The study outcomes were as follows: (1) incidence of metachronous primary GC after ER; and (2) predictors for the development of metachronous primary GC after ER by the Cox proportional hazards model. The median follow-up was 43.1months (1.81-79.1), and the 3-year cumulative incidence of metachronous primary GC was 6.5% (95%CI: 4.1-10.4). The incidence of metachronous primary GC during the follow-up period was 2.31 per 100 person-years. The frequencies of severe gastric atrophy and macrocytosis at the timing of ER were significantly higher in patients with than without metachronous primary GC (91.7% vs. 73.2%, p = 0.0422, 20.8% vs. 5.2%, p = 0.0046, respectively). Severe gastric atrophy was associated with the development of metachronous primary GC (sex-and-age adjusted hazard ratio (HR) [95%CI] = 4.12 [0.95-27.78], p = 0.0093). Macrocytosis was associated with the development of metachronous primary GC (sex-and-age adjusted HR = 4.76 [1.75-13.0], p = 0.0012) and found to be an independent predictor for metachronous primary GC by multivariate Cox proportional hazards analysis (HR [95%CI] = 4.35 [1.60-11.84], p = 0.004). Severe gastric atrophy and macrocytosis should be noted in the development of metachronous primary GC after ER for esophageal SCC. In particular, macrocytosis at the timing of ER was considered an important predictor. UMIN000001676.

Entecavir versus tenofovir disoproxil fumarate on the reduction of incidence of hepatocellular carcinoma in patients with chronic hepatitis B‐related liver cirrhosis

AbstractThis study aimed to compare the effect of long‐term continuous entecavir (ETV) compared with tenofovir disoproxil fumarate (TDF) on the reduction of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis B (CHB) related liver cirrhosis. This study recruited patients who had CHB‐related liver cirrhosis and received ETV or TDF treatment for more than 6 months. Regular assessments of ultrasonography and alpha‐fetoprotein test were arranged every 3 months for HCC detection. Five‐year cumulative incidence of HCC and risk factors for HCC development were analyzed. A total of 286 consecutive cirrhotic patients were included, 198 in the ETV group and 88 in the TDF group. During a median follow‐up of 57.5 months, 25 (12.6%) patients in the ETV group and 12 (13.6%) patients in the TDF group developed HCC. The 5‐year cumulative incidence of HCC was comparable between the ETV and TDF groups (6.57% vs. 9.09%, log‐rank p = .242). Multivariate Cox proportional hazard analysis revealed that male, old age, diabetes, and low platelet count were independent risk factors for HCC development. This study observed that long‐term ETV or TDF provided comparable preventive effects on HCC development in patients with CHB‐related liver cirrhosis.

Multicenter analysis of immunosuppressive medications on the risk of malignancy following adult solid organ transplantation.

This study aimed to assess the risk of maintenance immunosuppression on the post-transplant risk of malignancy across all solid organ transplant types. This is a retrospective cohort study from a multicenter hospital system in the United States. The electronic health record was queried from 2000 to 2021 for cases of solid organ transplant, immunosuppressive medications, and post-transplant malignancy. A total of 5,591 patients, 6,142 transplanted organs, and 517 post-transplant malignancies were identified. Skin cancer was the most common type of malignancy at 52.8%, whereas liver cancer was the first malignancy to present at a median time of 351 days post-transplant. Heart and lung transplant recipients had the highest rate of malignancy, but this finding was not significant upon adjusting for immunosuppressive medications (heart HR 0.96, 95% CI 0.72 - 1.3, p = 0.88; lung HR 1.01, 95% CI 0.77 - 1.33, p = 0.94). Random forest variable importance calculations and time-dependent multivariate cox proportional hazard analysis identified an increased risk of cancer in patients receiving immunosuppressive therapy with sirolimus (HR 1.41, 95% CI 1.05 - 1.9, p = 0.04), azathioprine (HR 2.1, 95% CI 1.58 - 2.79, p < 0.001), and cyclosporine (HR 1.59, 95% CI 1.17 - 2.17, p = 0.007), while tacrolimus (HR 0.59, 95% CI 0.44 - 0.81, p < 0.001) was associated with low rates of post-transplant neoplasia. Our results show varying risks of immunosuppressive medications associated with the development of post-transplant malignancy, demonstrating the importance of cancer detection and surveillance strategies in solid organ transplant recipients.

#3804 ASSOCIATION BETWEEN PLASMA XOR AND OUTCOMES IN CKD PATIENTS

Abstract Background and Aims Plasma xanthine oxidoreductase (pXOR) is an enzyme plays a key role in uric acid (UA) production and produces reactive oxygen species (ROS), and it has been reported that pXOR activity is related with cardiovascular events in the general population. However, the relationship between pXOR activity and prognosis in patients with chronic kidney disease (CKD) remains unclear. Method We measured pXOR activity by Liquid chromatography tandem quadruple mass spectrometer (LC-TQMS method) in 415 outpatients with CKD, and compared demographic and laboratory data between two groups based on the median pXOR activity. Furthermore, we examined the association between pXOR activity and outcomes; renal replacement therapy (RRT), major adverse cardiovascular events (MACE), and all-cause mortality, using multivariate Cox proportional hazards model. Results Median age and eGFR were 71 years old and 21.6 ml/min/1.73 m2, respectively. Median pXOR activity is 3.33 pmol/h/ml and 26.3 pmol/h/ml in the lower and higher pXOR activity groups, respectively. eGFR was significantly lower and UA was significantly higher in the lower pXOR activity group compared with the higher pXOR group (eGFR, 18.9 vs 27.4, P, &amp;lt;0.001; UA, 5.7 vs 6.1, P, &amp;lt;0.001). During the follow-up period of 38 months, the incidence of each outcome including RRT, MACE, or all-cause mortality were significantly higher in the lower pXOR group (log rank test, P&amp;lt;0.001). Multivariate Cox proportional hazards analysis including eGFR and UA levels showed that lower pXOR activity was significantly associated with poor renal? outcome (HR, 1.4; 95% CI, 1.0-2.1; P, 0.038). Furthermore, in subgroup analysis with or without antihyperuricemic use, univariate Cox analysis showed similar association between pXOR and each outcome. Conclusion In patients with CKD, lower pXOR activity has a significantly higher risk of all outcome (RRT, MACE, and all-cause mortality).

Association between triglyceride-glucose index and all-cause mortality in critically ill patients with ischemic stroke: analysis of the MIMIC-IV database

BackgroundThe triglyceride-glucose (TyG) index was significantly associated with insulin resistance (IR). Several studies have validated the effect of TyG index on cerebrovascular disease. However, the value of TyG index in patients with severe stroke requiring ICU admission remains unclear. The aim of this study was to investigate the association between the TyG index and clinical prognosis of critically ill patients with ischemic stroke (IS).MethodsThis study identified patients with severe IS requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC-IV) database, and divided them into quartiles based on TyG index level. The outcomes included in-hospital mortality and ICU mortality. The association between the TyG index and clinical outcomes in critically ill patients with IS was elucidated using Cox proportional hazards regression analysis and restricted cubic splines.ResultsA total of 733 patients (55.8% male) were enrolled. The hospital mortality and intensive care unit (ICU) mortality reached 19.0% and 14.9%, respectively. Multivariate Cox proportional hazards analysis showed that the elevated TyG index was significantly related to all-cause death. After confounders adjusting, patients with an elevated TyG index had a significant association with hospital mortality (adjusted hazard ratio, 1.371; 95% confidence interval, 1.053–1.784; P = 0.013) and ICU mortality (adjusted hazard ratio, 1.653; 95% confidence interval, 1.244–2.197; P = 0.001). Restricted cubic splines revealed that a progressively increasing risk of all-cause mortality was related to an elevated TyG index.ConclusionThe TyG index has a significant association with hospital and ICU all-cause death in critically ill patients with IS. This finding demonstrates that the TyG index might be useful in identifying patients with IS at high risk of all-cause death.

Prognostic impacts of geriatric nutritional risk index in patients with ischemic heart failure after percutaneous coronary intervention

Malnutrition has been proven to be associated with increased risk of poor prognosis in a series of diseases. This study explored the association between poor nutritional status and prognosis in patients with ischemic heart failure (IHF) undergoing percutaneous coronary intervention (PCI). The study enrolled 1745 patients with IHF undergoing PCI. The mean follow-up time was 28.7 months. Nutritional status was assessed by geriatric nutritional risk index (GNRI). All patients were divided into four groups according to GNRI quartiles (median and interquartile range: 103.8, 99.9-107.7). The primary endpoint was major adverse cardiovascular events (MACE), and the secondary endpoints were each component of the primary endpoint as follows: all-cause mortality, non-fatal myocardial infarction (MI), and any revascularization. The Kaplan-Meier survival analyses were performed to evaluate the incidence of the endpoints among 4 groups. The multivariate Cox proportional hazards analysis confirmed the independent effect of GNRI on the primary endpoint and secondary endpoints. The restricted cubic spline (RCS) was performed to evaluate the non-linear association of GNRI with MACE. The negative correlation of the GNRI with MACE (Log-rank P<0.001), all-cause mortality (Log-rank P<0.001) and any revascularization (Log-rank P<0.001) was confirmed through the Kaplan-Meier curves. Multivariate analysis showed that the decreased GNRI was independently related to increased risk of MACE (Quartile 1 versus Quartile 4: HR, 95% CI: 2.66, 2.01-3.51, P<0.001), all-cause mortality (Quartile 1 versus Quartile 4: HR, 95% CI: 2.33, 1.54-3.50, P<0.001) and any revascularization (Quartile 1 versus Quartile 4: HR, 95% CI: 3.42, 2.22-5.27, P<0.001). In addition, the non-linear association of GNRI with MACE was shown through RCS and the risk of MACE decreased as the GNRI increased in general (Non-linear P<0.001). Decreased GNRI was an independent risk factor of MACE in IHF patients undergoing PCI.

Long-Term Outcomes of Stereotactic Radiosurgery for Postoperative World Health Organization Grade I Skull Base Meningioma: Utility of Ki-67 Labeling Index as a Prognostic Indicator.

Gross total resection, without causing neurological deficits, is challenging in skull base meningioma (SBM). Therefore, stereotactic radiosurgery (SRS) is an important approach for SBMs; however, it is difficult to predict the long-term prognosis. To identify the predictive factors for tumor progression after SRS for World Health Organization (WHO) grade I SBMs, focusing on the Ki-67 labeling index (LI). In this single-center retrospective study, factors affecting progression-free survival rates (PFSs) and neurological outcomes in patients undergoing SRS for postoperative SBMs were evaluated. Based on the Ki-67 LI, patients were classified into 3 groups: low (<4%), intermediate (4%-6%), and high LI (>6%). In the 112 patients enrolled, the cumulative 5- and 10-year PFSs were 93% and 83%, respectively. The PFSs were significantly higher in the low LI group (95% at 10 years) compared with the other groups (intermediate LI, 60% at 10 years, P = .007; high LI, 20% at 10 years, P = .001). Multivariable Cox proportional hazard analysis demonstrated that the Ki-67 LI was significantly associated with the PFSs (low vs intermediate LI; hazard ratio, 6.00; 95% CI, 1.41-25.54; P = .015; low vs high LI; hazard ratio, 31.90; 95% CI, 5.59-181.77; P = .001). Ki-67 LI may be a useful predictor of long-term prognosis in SRS for postoperative WHO grade I SBM. SRS provides excellent long- and mid-term PFSs in SBMs with Ki-67 LIs <4% or 4% to 6%, with a low risk of radiation-induced adverse events.

Impact of estimated plasma volume status on clinical outcomes in patients with lower extremity artery disease who underwent endovascular therapy.

Lower extremity artery disease (LEAD) is an arterial occlusive disease associated with high morbidity and mortality. Estimated plasma volume status (ePVS), a marker of plasma volume expansion and contraction, is gaining attention in the field of cardiovascular diseases. However, the impact of ePVS on the clinical outcomes of patients with LEAD remains unclear. We calculated ePVS using two different formulas, Kaplan-Hakim (KH-ePVS) and Duarte (D-ePVS), in 288 patients (mean age, 73 years; 77% male) with LEAD who underwent the first endovascular therapy (EVT), and prospectively followed them up between 2014 and 2019. All patients were divided into two groups based on the median ePVS values. The primary endpoints were composite events, including all-cause death and major adverse limb events (death/MALE). The median follow-up duration was 672 days. There were 183, 40 and 65 patients in Fontaine classes II, III, and IV, respectively. The median KH-ePVS and D-ePVS was 5.96 and 5.09, respectively. The ePVS significantly increased with advancing Fontaine classes. Kaplan-Meier analysis demonstrated that the high ePVS group had higher rates of death/MALE than the low ePVS group. Multivariate Cox proportional hazard analysis revealed that each ePVS was an independent predictor for death/MALE after adjusting for confounding risk factors. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. ePVS was associated with LEAD severity and clinical outcomes, suggesting that ePVS could be an additional risk factor for death/MALE in patients with LEAD who underwent EVT. We demonstrated that the association between ePVS and the clinical outcomes of patients with LEAD. The prognostic ability for death/MALE was significantly improved by adding ePVS to the basic predictors. LEAD lower extremity artery disease, MALE major adverse limb events, PVS plasma volume status.

Long-term outcomes after cytoreductive nephrectomy and thrombectomy of patients with metastatic renal cell carcinoma with venous tumor thrombus: a retrospective study from a large Chinese center

BackgroundTargeted therapy combined with immunotherapy is the current first-line treatment for metastatic renal cell carcinoma (mRCC), but patients with tumor thrombus (TT) may suffer from lower limb edema or even sudden cardiac death, so the purpose of this study is to investigate the efficacy and safety of surgical treatment in patients with mRCC and TT and explore worse factors to affect the prognosis in this series of patients.Patients and methodsA total of 85 mRCC patients with TT who received cytoreductive nephrectomy and thrombectomy at our medical center from 2014 to 2023 are included. All patients received postoperative systemic therapy. Overall survival (OS) is defined as the time from surgery to death due to any reason or the last follow-up. Kaplan–Meier analysis was performed to evaluate OS and differences among groups were tested by log-rank. Multivariable Cox proportional hazards analysis was performed to ascertain independent relationships between clinicopathological factors and OS.ResultsThe median age of patients was 58 years old. Eleven patients (12.9%) had no symptoms, 39 patients (45.9%) had local symptoms, 15 patients (17.6%) had systemic symptoms, and 20 patients (23.5%) had both. Mayo grade of TT was 0, 1, 2, 3, and 4 for 12, 27, 31, 7, and 8 patients respectively. Fifty-five patients had lung metastasis, 23 had bone metastasis, 16 had liver metastasis, 13 had adrenal metastasis, and 9 had lymph node metastasis. Of all patients, 17 patients had multiple metastases. The median operation time is 289 min and the median intraoperative hemorrhage is 800 ml. Twenty-eight patients experienced postoperative complications, 8 of which were serious complications of modified Clavien grade III or higher. The median OS of all patients was 33 months and median follow up time was 26 months. In multivariate analysis, systemic symptom (p = 0.00753), pathological type (p = 0.0166), sarcomatous degeneration (p = 0.0334), and perirenal fat infiltration (p = 0.0202) are independent predictors of OS.ConclusionCytoreductive nephrectomy and thrombectomy is relatively safe and effective for patients with mRCC accompanied by TT. In this series of patients, the worse prognosis is associated with systemic symptoms, non-clear cell carcinoma, sarcomatous degeneration and perirenal fat infiltration.

Surgical Treatment Outcomes of Patients with Non-Small Cell Lung Cancer and Lymph Node Metastases

This study aimed to investigate the appropriate subgroups for surgery and adjuvant chemotherapy in patients with non-small-cell lung cancer (NSCLC) and nodal metastases. We retrospectively reviewed 210 patients with NSCLC and nodal metastases who underwent surgery and examined the risk factors for poor overall survival (OS) and recurrence-free probability (RFP) using multivariate Cox proportional hazards analysis. Pathological N1 and N2 were observed in 114 (52.4%) and 96 (47.6%) patients, respectively. A single positive node was identified in 102 patients (48.6%), and multiple nodes were identified in 108 (51.4%). Multivariate analysis revealed that vital capacity &lt; 80% (hazard ratio [HR]: 2.678, 95% confidence interval [CI]: 1.483–4.837), radiological usual interstitial pneumonia pattern (HR: 2.321, 95% CI: 1.506–3.576), tumor size &gt; 4.0 cm (HR: 1.534, 95% CI: 1.035–2.133), and multiple-node metastases (HR: 2.283, 95% CI: 1.517–3.955) were significant independent risk factors for poor OS. Tumor size &gt; 4.0 cm (HR: 1.780, 95% CI: 1.237–2.562), lymphatic permeation (HR: 1.525, 95% CI: 1.053–2.207), and multiple lymph node metastases (HR: 2.858, 95% CI: 1.933–4.226) were significant independent risk factors for recurrence. In patients with squamous cell carcinoma (n = 93), there were no significant differences in OS or RFP between those who received platinum-based adjuvant chemotherapy (n = 25) and those who did not (n = 68), at p = 0.690 and p = 0.292, respectively. Multiple-node metastases were independent predictors of poor OS and recurrence. Patients with NSCLC and single-node metastases should be considered for surgery despite N2 disease. Additional treatment with platinum-based adjuvant chemotherapy may be expected, especially in patients with squamous cell carcinoma.

Tp53 as a potential therapeutic biomarker in patients with recurrent high-grade glioma treated with anlotinib and temozolomide.

e14000 Background: Patients with recurrent high-grade glioma (rHGG) had a dismal prognosis. Previous studies have found that anlotinib is effective in treating rHGG, but there are no predictive biomarkers to select potential beneficiaries. Methods: The clinical and pathological data of patients with rHGG treated with anlotinib and temozolomide (TMZ) in our hospital were collected and analyzed. Treatment response was assessed according to Response Assessment in Neuro-Oncology criteria. Survival was estimated using the Kaplan-Meier curve with the log-rank test. Tumor protein 53 ( TP53), O-6-methylguanine-DNA methyltransferase, and pre-treatment peripheral blood index were evaluated for potential therapeutic biomarkers. Results: From August 2017 to February 2022, 23 eligible patients with rHGG were included in this study. The objective response rate was 52.2% (95% confidence intervals [CI]: 30.6-73.2%), and the disease control rate was 91.3% (95% CI: 72.0-98.9%). The median progress-free survival (PFS) for all patients was 5.3 months (95% CI: 4.9-5.7 months), with a 6-month PFS rate of 30.4% (95% CI: 13.2-52.9%). The median overall survival (OS) and the 12-month OS rate were 11.0 months (95% CI: 9.7-12.3) and 39.1% (95% CI: 19.7-61.5%), respectively. Patients with TP53 wild-type had significantly higher OS than those with TP53 mutant-type (13.0 months [95% CI: 10.5-15.5 months] vs. 9.0 months [95% CI: 7.4-10.6 months], p= 0.009). Multivariate cox proportional hazards analysis showed that TP53 was an independent prognostic biomarker for OS. Conclusions: The present study showed that anlotinib combined with TMZ had a promising efficacy in treating rHGG and TP53 was a potential biomarker to predict prognosis.

The Predictive Values of White Blood Cell Indices (Lymphocyte and Eosinophilic Granulocyte) for Heart Failure in Acute Coronary Syndrome Patients Following Percutaneous Coronary Intervention: A Prospective Cohort Study.

White blood cell (WBC) indices are strongly associated with cardiovascular disease, but data on the prognostic values of these parameters in patients with acute coronary syndrome (ACS) following percutaneous coronary intervention (PCI) are sparse. The current study aimed to investigate the relationship between baseline WBC indices levels and the incidence of heart failure (HF) in ACS patients after PCI and explore the predictive values over a 2-year follow-up period. A total of 416 consecutive ACS patients treated with PCI were enrolled and received a median of 27.7 months follow-up. Univariate and multivariate Cox regression analyses and the receiver operating characteristic (ROC) curves were performed. Baseline lymphocyte (LYMPH) count, eosinophil (EO) count and eosinophil percentage (EO %) were higher in patients who experienced HF over a 2-year follow-up. In multivariate Cox proportional hazards analysis, LYMPH count, EO count and EO % were independently associated with the occurrence of HF (hazard ratio [HR] = 12.876, P = 0.025; HR = 16.625, P = 0.004; HR = 1.196, P = 0.031, respectively). The area under the ROC curve of baseline EO count predicting the occurrence of HF in ACS patients following PCI was 0.625 (P = 0.037). For patients aged 60 years and above, who had PCI or history of coronary artery bypass grafting, the higher EO count, the higher the risk of HF. Elevated baseline LYMPH count, EO count and EO % were independently associated with the incidence of HF in ACS patients following PCI, suggesting that WBC indices might be available, simple, and cost-efficient biomarkers with predictive value, especially for patients aged more than 60 years.

Use of machine learning derived features from CT and H&amp;E whole-slide images to predict overall survival in head and neck squamous cell carcinoma.

6086 Background: Computed tomography (CT) and H&amp;E whole-slide images (WSI) have been found to carry rich prognostic information for patients diagnosed with head and neck squamous cell carcinoma (HNSCC). However, most machine learning models aimed for outcome prediction only took advantage of single image modality. In this work, we developed and validated a prognostic machine learning method incorporating both CT and WSI to predict overall survival in HNSCC patients. Methods: Matched radiographic CT scans and digitized WSI were acquired from the Cleveland Clinic for 167 HNSCC patients, including 120 HPV-associated oropharyngeal cancer and 47 laryngeal cancer. Both primary tumor and the largest suspicious lymph node were annotated on CT scans and primary tumor was delineated on H&amp;E WSI. We split the dataset into training and validation set using a 7:3 ratio, which resulted in 119 patients in the training set and 48 for hold-out validation. We applied a machine learning model (M_ML) using both CT and WSI as input to perform end-to-end predictions of overall survival. We used the harrell’s concordance index (C-index) to evaluate the prognostic performance. Finally, we performed the multivariable cox proportional hazard analysis adjusting for clinicopathological variables (i.e. age, gender, smoking pack-year [PY], AJCC 7th edition overall stage, and treatment modality) to validate the independent prognostic significance of the model. Results: The combined machine learning model M_ML (C-index = 0.81) outperformed the model using CT images alone (C-index = 0.63) and WSI alone (C-index = 0.64) on the validation set. In multivariable analysis, M_ML is still statistically significant accounting for clinicopathologic factors (p = 0.0007). Conclusions: This pilot study shows that a multi-omic machine learning model utilizing both radiographic CT and digitized WSI can predict HNSCC overall survival and outperforms models using only a single modality. [Table: see text]

PEDS3: Risk Factors for Thromboembolic Events in Pediatric Patients with Ventricular Assist Devices

Background: Pediatric patients on ventricular assist device (VAD) support are at risk of thromboembolic (TE) complications which include pump thrombosis, ischemic stroke, and transient ischemic attack. Methods: We conducted a retrospective chart review of pediatric patients implanted with Paracorporeal Pulsatile (PP) or Paracorporeal Continuous (PC) VADs between 2005-2022, at the Stollery Children’s Hospital (Edmonton, AB). Patients that transitioned from PC to PP were classified in a combination group. Patient and device related factors, including initial anti-coagulation strategies were collected. Kaplan Meier (KM) survival analysis was performed to determine freedom from TE event based on initial anti-coagulation strategy and VAD type. Univariate and multivariate Cox proportional hazard analysis was conducted to look for factors associated with TE events. Results: Of the 95 patients included, median age was 0.92 years (IQR 0.27, 5.37), median weight at implant was 8.4 kg (IQR 4.4, 18.0). Almost two-thirds (63%) had non congenital disease, with 47% supported on PC devices, 25% on PP devices, and 28% with a combination of devices. Initial anti-coagulation was with either Heparin (61.5%) or Bivalirudin (38.5%). Unadjusted freedom from a TE event was significantly higher in those who received Bivalirudin as their initial anti-coagulation strategy (p=0.022, Figure 1). KM analysis based on device type found that PC VADs predicted shorter freedom from TE events (p=0.012). In multivariate analysis, initial anticoagulation strategy (HR 0.359, 95% CI 0.165–0.785, p=0.01) for Bivalirudin was protective against events, while device type (HR 10.9, 95% CI 2.68–44.2, p<0.001), specifically PC devices, was found to be a predictor of TE events. Conclusions: This study suggests that device type, particularly PC, and heparin as an initial anti-coagulation strategy are risk factors TE events. Further work is needed to understand the interaction between device type and initial anti-coagulation strategy.

Impacts of androgen pathway manipulation on patients with lung cancer.

e21010 Background: Sex hormone may play a role in lung cancer pathophysiology. We aimed to evaluate if androgen pathway manipulation (APM) is associated with better survival in patients with lung cancer, and how finasteride, a 5-alpha reductase inhibitor, impacts androgen receptor (AR) activation and growth of lung cancer cells. Methods: In this retrospective hospital-based cohort study, we screened all men with lung cancer diagnosed during the period from January 2006 to December 2021. APM exposure was defined as using antiandrogens, 5-alpha reductase inhibitors, or gonadotropin-releasing hormone agonists for &gt; 30 days after lung cancer diagnosis. The in vitro study was conducted on A549 lung cancer cells; while the tumor xenograft model was conducted on BALB/c nude mice. Results: Among 4744 men with lung cancer, 98 (2.1%) were identified as having APM exposure. The majority of patients (73.5%) received 5-alpha reductase inhibitors. The patients with APM exposure were older (71.5 vs. 67.0, p &lt; 0.001), had a higher proportion of having prostate cancer (27.6% vs. 1.4%, p &lt; 0.001), and had a smaller proportion of having metastatic lung cancer (41.8% vs. 54.0%, p = 0.003), compared to those without APM exposure. In multivariable Cox proportional hazards analysis, patients with APM exposure experienced better OS compared to those without exposure (Hazard ratio 0.57; 95% CI, 0.44–0.73, p &lt; 0.001). In in vitro study, we illustrated that AR protein stimulated the cell proliferation of A549 cells. Finasteride reduced the AR protein expression and inhibited A549 cell growth. Finasteride promoted ubiquitination and degradation of AR protein and therefore interfered the stability of AR protein. Furthermore, finasteride inhibited cell cycle progression and promoted apoptosis of A549 cells. The in vivo results also supported the inhibition effect of finasteride on lung cancer growth. Conclusions: APM was associated with better OS in male patients with lung cancer. Finasteride interfered with the stability of AR and inhibited A549 lung cancer cell growth. Our findings indicated an oncogenic role of AR on lung cancer which may provide potential therapeutic and targets for lung cancer. The inhibition effect of finasteride on lung cancer might be of benefit for future treatment strategies, prevention and control.[Table: see text]

IDENTIFICATION OF GENOMIC BIOMARKERS OF DISEASE PROGRESSION AND SURVIVAL IN NEWLY‐DIAGNOSED PRIMARY CNS LYMPHOMA

Introduction: There is a significant unmet need for robust genomic biomarkers that identify patients with newly-diagnosed primary CNS lymphoma (PCNSL) at high risk of progression, both during standard methotrexate-based induction as well as after dose-intensive consolidation. Methods: We performed targeted next-generation sequencing of 529 cancer genes of formalin-fixed, paraffin-embedded tumors from 74 patients with newly diagnosed primary CNS diffuse large B-cell lymphoma using the UCSF500 Cancer Panel and the Institute for Human Genetics CLIA Laboratory. The assay detects structural variants including single nucleotide variants, small insertions and deletions, and copy-number alterations (CNAs). Sixty-four EBV-negative PCNSL patients treated with a standard methotrexate, temozolomide, rituximab (MTR) induction were available for complete analysis. Results: We identified frequent mutations involving MYD88 (77%), CD79B (41.9%), ETV6 (27%) and BTG1 (25.7%) as well as frequent CNA involving 6q loss (62.5%), 9p loss (34.4%) and 12 gain (31.3%). Three genomic alterations were most significantly associated with early disease progression in PCNSL: (1) Alterations at 6p21.3, predominantly copy neutral loss of heterozygosity (CN-LOH) at the HLA Class I (HLA-A, B, C) and Class II loci (HLA-DR, DP, DQ, TAP1) as well as homozygous deletion of HLA Class II; (2) Mutations of tumor suppressor genes BTG1 and ETV6. Overall, these genomic alterations were detected in 28 out of 31 progression events in the cohort. The subgroup with either CN-LOH or homozygous deletion at 6p had the earliest progression, followed by the subgroup with mutations at either BTG1/ETV6 and no 6p CN-LOH or homozygous deletion, compared to no alterations at these 3 loci. 10 of 18 tumors with these alterations at 6p also contained BTG1 and/or ETV6 mutations. Survival analysis demonstrates that the subgroup with 6p CN-LOH or homozygous deletion had the earliest progression, followed by the subgroup with BTG1/ETV6 mutations compared to no alterations at these 3 loci (PFS p = 3.7e-5, OS p = 0.0017, logrank test, Figure 1). Multivariate Cox proportional hazard analysis demonstrated a significant 3.24-fold increased risk of progression with 6p CN-LOH/homozygous deletion or BTG1/ETV6 mutations (p = 3.5e-5, adjusted by Age, KPS, IELSG, MSKCC, IOL, Maintenance, and Consolidation). The research was funded by: National Cancer Institute NIH R01CA139-83-01A1 Keywords: aggressive B-cell non-Hodgkin lymphoma, diagnostic and prognostic biomarkers, genomics, epigenomics, and other-omics No conflicts of interests pertinent to the abstract.

Factors affecting survival after liver retransplantation: a systematic review and meta-analysis.

Liver retransplantation (reLT) has historically had inferior survival relative to primary liver transplant (LT). To improve outcomes after reLT, researchers have identified factors predicting overall (OS) and/or graft survival (GS) after reLT. This systematic review and random effects meta-analysis sought to summarize this literature to elucidate the strongest independent predictors of post-reLT. A systematic review was conducted to identify manuscripts reporting factors affecting survival in multivariable Cox proportional hazards analyses. Papers with overlapping cohorts were excluded. All 25 included studies were retrospective, and 15 (60%) were single-center studies. Patients on pre-transplant ventilation (HR, 3.11; 95% CI, 1.56-6.20; p = 0.001) and with high serum creatinine (HR, 1.46; 95% CI, 1.15-1.87; p = 0.002) had the highest mortality risk after reLT. Recipient age, Model for End-Stage Liver Disease score, donor age, and cold ischemia time >12 h also conferred a significant risk of post-reLT death (all p < 0.05). Factors affecting GS included donor age and retransplant interval (the time between LT and reLT; both p < 0.05). OS is significantly higher when the retransplant interval is ≤7 days relative to 8-30 days (p = 0.04). The meta-analysis was complicated by papers utilizing non-standardized cut-off values to group variables, which made between-study comparisons difficult. However, it did identify 7 variables that significantly impact survival after reLT, which could stimulate future research into improving post-reLT outcomes.

Nocturnal pulse wave amplitude attenuations are associated with long-term cardiovascular events

ObjectivesPhotoplethysmography (PPG) is an established technology for detecting pulse rate and pulse wave irregularities. However, whether temporal variations in pulse wave amplitudes, reflecting a combination of acute hemodynamic or autonomic responses to changes in overall vascular function, carry prognostic information remains unclear. To quantify nocturnal temporal pulse wave amplitude (PWA) attenuations and evaluate its association with long-term cardiovascular (CV) events in a large, racially diverse sample of men and women. MethodsTemporal PWA attenuations were determined based on the slopes between the upper and lower envelopes of PPGs derived from overnight polysomnography of 1957 participants (899 men, 1058 women, mean age 68.2 ± 9.1 years) of the Multi-Ethnic Study of Atherosclerosis. The nocturnal PWA attenuation index was defined as the cumulative duration of all PWA attenuation events relative to total sleep duration. ResultsNocturnal PWA attenuation index was greater in men than in women by almost 13% (16.3 ± 8.9% vs. 14.4 ± 7.9%, p < 0.001). The nocturnal PWA attenuation index was highest in Chinese-American participants (17.9 ± 9.2%) and lowest in African-Americans (13.5 ± 8.1%). During a median follow-up of 4.9 years, 94 CV events occurred. In multivariable Cox proportional hazard analysis adjusted for typical confounders, the nocturnal PWA attenuation index <15.2% was associated with CV events (HR = 1.58 [1.02–2.45], p = 0.042). ConclusionsNocturnal PWA attenuation index is inversely associated with the risk of CV events, particularly in men and African-Americans. The PPG-derived nocturnal PWA attenuation index could be simply obtained from smart wearable consumer devices and may provide a low-cost, accessible and scalable CV risk marker.

Factors related with survival in men and women with heart failure

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): The study was supported by an intramural research grant from the National Institute of Cardiology. Background Heart failure (HF) is a significant cause of morbidity and mortality in both women and men. The discrepancies in the underlying mechanisms and etiology of HF in both sexes suggest that factors related to the prognosis of HF and the risk of death may also be different in men and women. Objective The aim of the study was to identify factors related with survival in men and women with HF. Methods Patients from a hospital database coded as hospitalizations for HF between 01/2014 and 05/2019 were included in the analysis. In all patients, the diagnosis of HF was verified. Information on HF, comorbidities, and death was obtained from available medical records. Kaplan-Meier survival curves were generated to analyze time-to-event data and to compare survival in both men and women. Multivariable Cox proportional hazard analysis was used to evaluate the risk of death and related factors. Results 1824 (70.1%) men and 777 (29.9%) women were included. Women were older than men (68.3 vs. 62.4 years; p&amp;lt;0.001). The median follow-up time (2.43 vs. 2.42 years; p=0.550), and the proportion of all deaths during follow-up were similar in men and women (37.8 vs. 34.5%; p=0.112). The Kaplan-Meier survival curves by sex were alike (p=0.2732) and are presented in Figure 1. The results of the multivariable Cox proportional hazards analysis are presented in Table 1. In both men and women respectively, after adjustment for other covariates, a significant association with an increased risk of death was documented for: catecholamines (HR=2.27 and HR=2.92), significant tricuspid regurgitation (HR=1.46 and HR=1.66), renal failure (HR=1.59 and HR=1.68), liver failure (HR=1.90 and HR=2.44), anemia (HR=1.51 and HR=1.46) and emergency admission (HR=1.21 and HR=1.77). The optimal dose of ACEI was associated with a decreased risk of death in both sexes (HR=0.75 in men and HR=0.60 in women). In men, we also found that other factors, such as diuretics (HR=2.29), chronic HF (HR=1.87), ischemic etiology (HR=1.40), atherosclerosis (HR=1.37), stroke (HR = 1.28), cardioverter defibrillator implantation (HR=1.27), ventricular arrythmias (HR=1.24), and age (HR=1.02) were related with a higher risk of death. Furthermore, only in women a higher risk of death was associated with dementia (HR=2.26), hypertension (HR=1.81), amiodarone (HR=1.68), aortic stenosis (HR=1.52), and myocardial infarction (HR=1.46), while a lower risk was found for an increasing number of comorbidities (HR=0.86). Conclusions Overall survival in men and women with HF was similar, as well as the strength and direction of the relationship with the risk of death in common risk factors. However, some of the predictors of death differed between men and women, which should draw our attention to potential differences in gender-related parameters affecting survival in HF.

Autoimmune, Inflammatory, Atopic, Thyroid, and Psychiatric Outcomes of Offspring Born to Mothers With Alopecia Areata

Alopecia areata (AA) is associated with diverse autoimmune and psychiatric disorders. However, an investigation on the long-term outcomes for offspring born to mothers diagnosed with AA is lacking. To investigate the risks for autoimmune, inflammatory, atopic, thyroid, and psychiatric outcomes of offspring born to mothers with AA. This retrospective population-based birth cohort study used the linked birth registration database with the Nationwide Health Insurance Service database of Korea. The participants included all newborns born to mothers with 3 or more visits with International Classification of Diseases, Tenth Revision code of L63 and 1:10 birth year, sex, insurance, income, and location of residence-matched control offspring born to mothers without AA during the years from 2003 to 2015. The analysis was conducted from July 2022 to January 2023. Maternal AA. The occurrence of the following diseases was measured in newborns from birth to December 31, 2020: AA, alopecia totalis/universalis (AT/AU), vitiligo, psoriasis, inflammatory bowel disease, rheumatoid arthritis, atopic dermatitis, allergic rhinitis, asthma, hyperthyroidism, hypothyroidism, Graves disease, Hashimoto thyroiditis, attention-deficit hyperactivity disorder, mood disorder, and anxiety disorder. Multivariable Cox proportional hazard analyses were performed with the following covariates: birth year, age, insurance type, income level, location of residence, maternal age, mode of delivery, maternal history of atopic disorders, and autoimmune disorders. In total, 67 364 offspring born to 46 352 mothers with AA and 673 640 controls born to 454 085 unaffected mothers were analyzed. The risk of AA (adjusted hazard ratio [aHR], 2.08; 95% CI, 1.88-2.30), AT/AU (aHR, 1.57; 95% CI, 1.18-2.08), vitiligo (aHR, 1.47; 95% CI, 1.32-1.63), atopic disorders (aHR, 1.07; 95% CI, 1.06-1.09), hypothyroidism (aHR, 1.14; 95% CI, 1.03-1.25), and psychiatric disorders (aHR, 1.15; 95% CI, 1.11-1.20) was significantly increased in offspring born to mothers with AA. Among them, 5088 born to mothers with AT/AU were at much greater risk for the development of AT/AU (aHR, 2.98; 95% CI, 1.48-6.00) and psychiatric disorders (aHR, 1.27; 95% CI, 1.12-1.44). In this Korean retrospective population-based birth cohort study, maternal AA was associated with the development of autoimmune/inflammatory, atopic, thyroid, and psychiatric disorders in their offspring. Clinicians and parents need to be aware of the potential for these comorbidities to occur.