Multivariate Cox Regression Model Research Articles

The association between liver fibrosis score and incident dementia: A nationwide retrospective cohort study.

We assessed the relationship of liver fibrosis score with incident dementia in a large, national sample. For this retrospective cohort study, data of dementia-free individuals aged 40-69 years were derived from electronic records of the largest healthcare provider in Israel. The association between liver fibrosis score (FIB-4), assessed from routine laboratory measurements, and incident dementia was explored through multivariate cox regression models. Of the total sample (N=826,578, mean age 55±8 years at baseline), 636,967 (77%) had no fibrosis, 180,114 (21.8%) had inconclusive fibrosis status and 9497 (1.2%) had high risk for advanced fibrosis. Over a median follow-up of 17 years, 41,089 dementia cases were recorded. Inconclusive liver fibrosis and advanced fibrosis were associated with increased dementia risk (HR=1.09, 95%CI: 1.07-1.11 and HR=1.18, 95%CI: 1.10-1.27, respectively). This association remained robust through seven sensitivity analyses. Liver fibrosis assessed through a serum-based algorithm may serve as a risk factor for dementia in the general population. Liver fibrosis may predict dementia diagnosis in the general population. Inconclusive liver fibrosis was associated with 9% increased dementia risk. Advanced liver fibrosis was associated with 18% increased dementia risk. Findings remained robust in sensitivity analyses and after adjustments.

Cardiac arrest and cardiogenic shock complicating ST-segment elevation myocardial infarction in China: A retrospective multicenter study

BackgroundData on the effect of cardiac arrest (CA), cardiogenic shock (CS), and their combination on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI) are limited. The present study sought to evaluate the clinical outcomes of STEMI complicated by CA and CS, and to identify the risk factors for CA or CS. MethodsThis study included 7468 consecutive patients with STEMI in China. The patients were divided into 4 groups (CA + CS, CA only, CS only, and No CA or CS). The endpoints were 30-day all-cause death and major adverse cardiovascular events. A Cox proportional hazards regression analysis was performed. ResultsCA, CS, and their combination were noted in 332 (4.4 %), 377 (5.0 %), and 117 (1.6 %) among all patients. During the 30-day follow-up, 817 (10.9 %) all-cause deaths and 964 (12.9 %) major adverse cardiovascular events occurred, and the incidence of all-cause mortality (3.6 %, 62.3 %, 74.1 %, 83.3 %) and major adverse cardiovascular events (5.4 %, 67.1 %, 75.0 %, and 87.2 %) significantly increased in the No CA or CS, CS only, CA only, and CA + CS groups, respectively. In the multivariate Cox regression models, compared with the No CA or CS group, the CA + CS, CA, and CS-only groups were associated with an increased risk of all-cause death and major adverse cardiovascular events. Patients with CA + CS had the highest risk of all-cause death (hazard ratio [HR], 25.259 [95 % confidence interval (CI) 19.221–33.195]) and major adverse cardiovascular events (HR 19.098, 95%CI 14.797–24.648). ConclusionsCA, CS, and their combination were observed in approximately 11 % of Chinese patients with STEMI, and were associated with increased risk for 30-day mortality and major adverse cardiovascular events in Chinese patients with STEMI.

Association between dietary magnesium intake and all-cause mortality among patients with diabetic retinopathy: a retrospective cohort study of the NHANES 1999-2018.

This study aimed to investigate the association between dietary magnesium intake and all-cause mortality among diabetic retinopathy (DR) patients. In this retrospective cohort study, data of 1,034 DR patients were extracted from the National Health and Nutrition Examination Survey (NHANES) (1999-2018). Dietary magnesium data were obtained from two 24-hour dietary recall interviews, and categorized into quartiles. Potential confounders were selected using weighted univariate Cox regression models. Weighted univariate and multivariate Cox regression models were used to explore the association between dietary magnesium intake and all-cause mortality in DR patients. The results were presented with hazard ratios (HRs) and 95% confidence intervals (CIs). Associations were further explored for subgroups related to age, gender, cardiovascular disease, and chronic kidney disease. Our study included 1,034 DR patients, of whom 438 (42.36%) died. The mean age of all patients was 63.26 (0.51) years old, with a median follow-up time of 75.00 months. Higher magnesium intake was associated with lower all-cause mortality risk (HR=0.58, 95%CI: 0.38-0.88) in DR patients. The association remained for those aged <65 years (HR=0.35, 95%CI: 0.15-0.81), male patients (HR=0.48, 95%CI: 0.27-0.84), patients without chronic kidney disease (HR=0.43, 95%CI: 0.23-0.82), and patients with a history of cardiovascular disease (HR=0.63, 95%CI: 0.39-1.02). DR patients with adequate magnesium intake exhibited a lower incidence of all-cause mortality. Further studies are needed to validate our findings and explore the optimal strategy for magnesium supplementation in DR patients.

Left ventricular mass as a modulator of ventricular arrhythmia risk and sex differences after CRT for nonischemic cardiomyopathy and LBBB

BackgroundThe risk of ventricular arrhythmias (VAs) after cardiac resynchronization therapy (CRT) has been associated with ischemic disease/scar, sex, and possibly left ventricular mass (LVM). ObjectiveThe purpose of this study was to evaluate sex differences and baseline/postimplant change in LVM on VA risk after CRT implantation in patients with nonischemic cardiomyopathy and left bundle branch block. MethodsIn patients meeting the criteria, baseline and follow-up echocardiographic images were obtained for LVM assessment. VA events were reported from device diagnostics and therapies. VA risk was stratified by receiver operating characteristic (Youden index cutoff point) for baseline LVM and baseline/postimplant change in LVM. Multivariate Cox regression model was also used for VA risk stratification. ResultsOne hundred eighteen patients (71 female patients [60.2%]; mean age 60.5 ± 11.3 years; left ventricular ejection fraction 19.2% ± 7.0%; QRS duration 165.6 ± 20 ms; LVM 313.9 ± 108.8 g) were enrolled and followed up for a median of 90 months (interquartile range 44–158 months). Thirty-five patients (29.6%) received appropriate shocks or antitachycardia pacing at a median of 73.5 months (interquartile range 25–130 months) postimplantation. Males had a higher VA incidence (male patients 18 of 47 [38.3%] vs female patients 17 of 71 [23.9%]; P = .02). Baseline LVM > 308.9 g separated patients with higher VA risk (P = .001). Less than a 20% decrease in LVM increased VA risk (P < .001). Baseline LVM was the only baseline characteristic predicting VA events in the Cox regression model (hazard ratio 1.01; 95% confidence interval 1.001–1.009; log-rank, P = .003). Sex differences in VA risk were eliminated by the baseline LVM parameters. ConclusionVA risk after CRT implantation in nonischemic cardiomyopathy was associated with baseline LV > 308.9 g and a decrease in LVM ≤ 20%, without sex differences.

Prognostic Value of Coronary Microvascular Dysfunction Assessed by Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

CaIMR is proposed as a novel angiographic index designed to assess microcirculation without the need for pressure wires or hyperemic agents. We aimed to investigate the impact of caIMR on predicting clinical outcomes in STEMI patients. One hundred and forty patients with STEMI who received PCI in Putuo Hospital of Shanghai from October 2021 to September 2022 were categorized into CMD and non-CMD groups according to the caIMR value. The baseline information, patient-related examinations, and the occurrence of MACE at the 12-month follow-up were collected to investigate risk factors in patients with STEMI. We divided 140 patients with STEMI enrolled into two groups according to caIMR results, including 61 patients diagnosed with CMD and 79 patients diagnosed with non-CMD. A total of 21 MACE occurred during the 1 year of follow-up. Compared with non-CMD group, patients with CMD showed a significantly higher risk of MACE. A multivariate Cox regression model was conducted for the patients, and it was found thatcaIMR was a significant predictor of prognosis in STEMI patients (HR: 8.921). Patients with CMD were divided into culprit vascular CMD and non-culprit vascular CMD, and the result found that culprit vascular CMD was associated with the incidence of MACE (OR: 4.75) and heart failure (OR: 7.50). CaIMR is a strong predictor of clinical outcomes and can provide an objective risk stratification for patients with STEMI. There is a strong correlation among leukocyte index, the use of furosemide, Killips classification, and clinical outcomes.

Role of Pathologic Single-Nodal and Multiple-Nodal Descriptors in Resected Non-Small Cell Lung Cancer

BackgroundThe 8th edition of lung cancer N staging assignment includes the location of lymph node metastasis, but does not include single- and multiple-N descriptors. Research QuestionDo the single- and multiple-N statuses stratify the prognosis of patients with non-small cell lung cancer (NSCLC)? Study Design and MethodsUsing the National Cancer Database, we analyzed patients with pathologically staged N1–2 NSCLC. N descriptors were classified into pathological single N1 (pSingle-N1), pathological multiple N1 (pMulti-N1), pSingle-N2, and pMulti-N2. Survival analysis was performed using Kaplan–Meier method and multivariate Cox regression models. ResultsIn the general analysis cohort, 24,531, 22,256, 8,528, and 21,949 NSCLC patients had pSingle-N1, pMulti-N1, pSingle-N2, and pMulti-N2, respectively. Patients with pMulti-N1 and pMulti-N2 had a shorter survival than those with pSingle-N1 and pSingle-N2, respectively (hazard ratio [HR]: 1.22, P < 0.0001 for N1 and 1.39, P < 0.0001 for N2). After adjusting age, sex, and histology, the HR for pSingle-N2 compared with pMulti-N1 was 1.05 (P = 0.0031). Patients with pN1 were categorized by metastatic lymph node count (1, 2, 3, 4+), showing significant prognostic differences among groups (P < 0.0001). In the sensitivity analysis cohort (limited to R0 resection, lobectomy or more, survival ≥ 30 days, ≥ 10 examined lymph nodes, and without neoadjuvant therapy; n = 34,904) and the external validation cohort (n = 708) analyses supported these results. InterpretationNSCLC patients with 1 metastatic lymph node, whether in N1 or N2 stations, had better survival than those with more than 1 lymph node involved. NSCLC patients with a single skip N2 lymph node metastasis had survival similar to patients with multiple N1 lymph nodes, and the number of lymph nodes involved in N1 resections up to ≥ 4 was sequentially prognostic.

Pseudomonas aeruginosa infection correlates with high MFI donor-specific antibody development following lung transplantation with consequential graft loss and shortened CLAD-free survival

BackgroundDonor-specific antibodies (DSAs) are common following lung transplantation (LuTx), yet their role in graft damage is inconclusive. Mean fluorescent intensity (MFI) is the main read-out of DSA diagnostics; however its value is often disregarded when analyzing unwanted post-transplant outcomes such as graft loss or chronic lung allograft dysfunction (CLAD). Here we aim to evaluate an MFI stratification method in these outcomes.MethodsA cohort of 87 LuTx recipients has been analyzed, in which a cutoff of 8000 MFI has been determined for high MFI based on clinically relevant data. Accordingly, recipients were divided into DSA-negative, DSA-low and DSA-high subgroups. Both graft survival and CLAD-free survival were evaluated. Among factors that may contribute to DSA development we analyzed Pseudomonas aeruginosa (P. aeruginosa) infection in bronchoalveolar lavage (BAL) specimens.ResultsHigh MFI DSAs contributed to clinical antibody-mediated rejection (AMR) and were associated with significantly worse graft (HR: 5.77, p < 0.0001) and CLAD-free survival (HR: 6.47, p = 0.019) compared to low or negative MFI DSA levels. Analysis of BAL specimens revealed a strong correlation between DSA status, P. aeruginosa infection and BAL neutrophilia. DSA-high status and clinical AMR were both independent prognosticators for decreased graft and CLAD-free survival in our multivariate Cox-regression models, whereas BAL neutrophilia was associated with worse graft survival.ConclusionsP. aeruginosa infection rates are elevated in recipients with a strong DSA response. Our results indicate that the simultaneous interpretation of MFI values and BAL neutrophilia is a feasible approach for risk evaluation and may help clinicians when to initiate DSA desensitization therapy, as early intervention could improve prognosis.

Outcomes and Baseline Predictors of Failure in Primary Standalone Xen45 Gel Stent versus Trabeculectomy for Glaucoma

PurposeTo compare safety, effectiveness and baseline predictors of failure in standalone primary Xen45 gel stent (Xen) vs trabeculectomy (Trab) in glaucoma. DesignRetrospective study SubjectsSubjects that underwent primary Xen or Trab augmented by mitomycin-C with at least 12 months follow-up. MethodsMultinational observational study of eyes in the Fight Glaucoma Blindness international registry Main outcome measuresThe primary outcome was success at 12 months defined by IOP reduction ≥ 20% from baseline and ≤ threshold IOPs of 15mmHg, 18mmHg and 21mmHg with (qualified) or without (complete) medications and without secondary glaucoma surgery. Multivariable mixed effects cox regression models were used to identify risk factors for failure in each cohort. Results701 eyes (Xen, 308; Trab, 393) of 596 subjects were included with baseline IOP being significantly higher (22.4 vs 19.9 mmHg, p < 0.001) and baseline medications significantly lower in the Xen vs the Trab group (2.9 vs 3.4, p <0.001). Baseline visual field (VF) mean deviation (MD) was less severe in the Xen group (-9.47 vs -13.04 dB, p < 0.001). The proportion of complete surgical success was significantly lower in the Xen vs Trab group across the three upper IOP limits at 12 months; 32% vs 52% at 15mmHg, 37% vs 54% at 18mmHg, and 39% vs 55% at 21mmHg (p < 0.001). The incidence of post-operative numerical and symptomatic hypotony was lower in the Xen vs Trab group. In the Xen cohort, a higher failure rate was associated with Asian ethnicity (HR, 1.97; 95% CI, 1.03-3.79) and use of oral acetazolamide at baseline (HR, 1.74; 1.13-2.70), while a lower failure rate was associated with diagnosis of ocular hypertension/open angle glaucoma suspect (HR, 0.52; 0.28-0.94) and secondary open angle glaucoma (HR, 0.45; 0.25-0.8). Exposure to prostaglandin analogue was associated with greater failure in the Trab group (HR, 2.66; 1.18-6.01). ConclusionsThere was significantly greater complete success at 12 months across all complete success definitions for Trab compared to Xen, while the rate of post-operative hypotony was significantly lower in Xen group. Asian ethnicity and use of oral acetazolamide at baseline were associated with greater failure in Xen, while exposure to prostaglandin analogue was associated with greater failure in Trab patients. Such baseline predictors of success and failure may help guide patient selection for subconjunctival minimally invasive glaucoma surgery in patients undergoing surgical intervention.

The impact of revascularization strategy on clinical failure, hemodynamic failure, and chronic limb-threatening ischemia symptoms in the BEST-CLI Trial

ObjectiveSustained clinical and hemodynamic benefit after revascularization for chronic limb-threatening ischemia (CLTI) is needed to resolve symptoms and prevent limb loss. We sought to compare rates of clinical and hemodynamic failure as well as resolution of initial and prevention of recurrent CLTI after endovascular (ENDO) vs bypass (OPEN) revascularization in the Best-Endovascular-versus-best-Surgical-Therapy-in-patients-with-CLTI (BEST-CLI) trial. MethodsAs planned secondary analyses of the BEST-CLI trial, we examined the rates of (1) clinical failure (a composite of all-cause death, above-ankle amputation, major reintervention, and degradation of WIfI stage); (2) hemodynamic failure (a composite of above-ankle amputation, major and minor reintervention to maintain index limb patency, failure to an initial increase or a subsequent decrease in ankle brachial index of 0.15 or toe brachial index of 0.10, and radiographic evidence of treatment stenosis or occlusion); (3) time to resolution of presenting CLTI symptoms; and (4) incidence of recurrent CLTI. Time-to-event analyses were performed by intention-to-treat assignment in both trial cohorts (cohort 1: suitable single segment great saphenous vein [SSGSV], N = 1434; cohort 2: lacking suitable SSGSV, N = 396), and multivariate stratified Cox regression models were created. ResultsIn cohort 1, there was a significant difference in time to clinical failure (log-rank P < .001), hemodynamic failure (log-rank P < .001), and resolution of presenting symptoms (log-rank P = .009) in favor of OPEN. In cohort 2, there was a significantly lower rate of hemodynamic failure (log-rank P = .006) favoring OPEN, and no significant difference in time to clinical failure or resolution of presenting symptoms. Multivariate analysis revealed that assignment to OPEN was associated with a significantly lower risk of clinical and hemodynamic failure in both cohorts and a significantly higher likelihood of resolving initial and preventing recurrent CLTI symptoms in cohort 1, including after adjustment for key baseline patient covariates (end-stage renal disease [ESRD], prior revascularization, smoking, diabetes, age >80 years, WIfI stage, tissue loss, and infrapopliteal disease). Factors independently associated with clinical failure included age >80 years in cohort 1 and ESRD across both cohorts. ESRD was associated with hemodynamic failure in cohort 1. Factors associated with slower resolution of presenting symptoms included diabetes in cohort 1 and WIfI stage in cohort 2. ConclusionsDurable clinical and hemodynamic benefit after revascularization for CLTI is important to avoid persistent and recurrent CLTI, reinterventions, and limb loss. When compared with ENDO, initial treatment with OPEN surgical bypass, particularly with available saphenous vein, is associated with improved clinical and hemodynamic outcomes and enhanced resolution of CLTI symptoms.

Development of Desmoid Tumors After Ileorectal Anastomosis Versus Ileal Pouch-Anal Anastomosis in Familial Adenomatous Polyposis

Background & AimsDesmoid tumours (DT) are an important cause of morbidity and mortality in patients with familial adenomatous polyposis (FAP). DT development might be related to the type and approach of colectomy. We aimed to compare DT development after colectomy with ileorectal anastomosis (IRA) and proctocolectomy with ileal pouch-anal anastomosis (IPAA). MethodsWe performed an international historical cohort study in FAP patients who underwent IRA or IPAA between 1961 and 2020. The primary outcome was the incidence of abdominal DT (either mesenteric, retroperitoneal or abdominal wall). Patients with a DT diagnosis before or at colectomy were excluded. Time to DT was considered censored at an eventual secondary proctectomy after IRA. We used multivariable Cox regression modelling to adjust for potential confounders. ResultsWe analysed data from 852 patients: 514 after IRA and 338 after IPAA (median follow-up 21 and 16 years, respectively). DTs were diagnosed in 64 IRA patients (12%) and 66 IPAA patients (20%). The cumulative DT incidence at 5 and 10 years was 7.5% and 9.3% after open IRA and 4.7% and 10.9% after laparoscopic IRA. These estimates were 13.6% and 15.4% after open IPAA and 8.4% and 10.0% after laparoscopic IPAA. The post-operative risk was significantly higher after IPAA (p < 0.01) in multivariable analysis, while approach did not significantly influence the risk. ConclusionsThe risk of developing an abdominal DT was found to be significantly higher after IPAA than after IRA. Postoperative DT risk should be taken into account when choosing between IRA and IPAA in FAP.

Organ-confined pT2 ISUP4/5 vs. nonorgan confined pT3/4 ISUP2 vs. ISUP3 prostate cancer: Differences in biochemical recurrence-free survival after radical prostatectomy

BackgroundTo test for differences in organ-confined pathological tumor stage (pT) and intermediate International Society of Urological Pathologists (ISUP) grade vs. nonorgan confined pT stage and high ISUP grade and biochemical recurrence (BCR) after radical prostatectomy (RP). MethodsRelying on a tertiary-care database, prostate cancer patients undergoing RP between January 2014 and December 2021 were stratified according to their combination of pT stage and ISUP grade in RP specimens (pT2 ISUP4/5 vs. pT3/4 ISUP2 vs. pT3/4 ISUP3). As Active Surveillance is recommended in ISUP1, these patients were excluded. Moreover, patients with pT2 ISUP2/3 are known for their good prognosis and pT3/4 ISUP4/5 patients for their poor prognosis. Therefore, these patients were also excluded from analyses. Kaplan–Meier survival analyses and multivariable Cox regression models addressed BCR after RP. ResultsOf 215 RP patients, 29 (13%) exhibited pT2 ISUP4/5 vs. 122 (57%) pT3/4 ISUP2 vs. 64 (30%) pT3/4 ISUP3 pathology. In survival analyses, 3-year BCR-free survival rates were 95% in pT2 ISUP4/5 vs. 88% in pT3/4 ISUP2 vs. 65% in pT3/4 ISUP3 patients (P < 0.001). In multivariable Cox regression models addressing BCR, pT3/4 ISUP3 pathology was associated with higher BCR rate relative to pT2 ISUP4/5 pathology (hazard ratio 3.42, 95% confidence interval 1.07-10.94; P = 0.039), but not pT3/4 ISUP2 pathology (P = 0.6). ConclusionCompared to prostate cancer patients with pT2 ISUP4/5 pathology, the combination of pT3/4 ISUP3 pathology is associated with higher risk of BCR after RP. In consequence, patients with pT3/4 ISUP3 pathology should be considered for a closer postoperative follow-up.

Regional Differences in Stage III Nonseminoma Germ Cell Tumor Patients Across SEER Registries

PurposeWe investigated regional differences in patients with stage III nonseminoma germ cell tumor (NSGCT). Specifically, we investigated differences in baseline patient, tumor characteristics and treatment characteristics, as well as cancer-specific mortality (CSM) across different regions of the United States. MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database (2004-2018), patient (age, race/ethnicity), tumor (International Germ Cell Cancer Collaborative Group [IGCCCG] prognostic groups) and treatment (systemic therapy and retroperitoneal lymph dissection [RPLND] status) characteristics were tabulated for stage III NSGCT patients, according to 12 SEER registries representing different geographic regions. Multinomial regression models and multivariable Cox regression models testing for cancer-specific mortality (CSM) were used. ResultsIn 3,174 stage III NSGCT patients, registry-specific patient counts ranged from 51 (1.5%) to 1630 (51.3%). Differences across registries existed for age (12%-31% for age 40+), race/ethnicity (5%-73% for others than non-Hispanic whites), IGCCCG prognostic groups (24%-43% vs. 14-24% vs. 3%-20%, in respectively poor vs. intermediate vs. good prognosis), systemic therapy (87%-96%) and RPLND status (12%-35%). After adjustment, clinically meaningful inter-registry differences remained for systemic therapy (84%-97%) and RPLND (11%-32%). Unadjusted 5-year CSM rates ranged from 7.1% to 23.3%. Finally in multivariable analyses addressing CSM, 2 registries exhibited more favorable outcomes than SEER registry of reference (SEER Registry 12): SEER Registry 4 (Hazard Ratio (HR): 0.36) and SEER Registry 9 (HR: 0.64; both P = .004). ConclusionWe identified important regional differences in patient, tumor and treatment characteristics, as well as CSM which may be indicative of regional differences in quality of care or expertise in stage III NGSCT management.

Prognostic significance of C-reactive protein/albumin and neutrophil/lymphocyte ratios in patients with COVID-19

Introduction and aim. COVID-19 causes an uncontrolled and generalized inflammatory response of the host immune system. Early recognition of the disease and early prediction of the clinical course are of great importance. The aim of this study was to evaluate the predictive role of the C-reactive protein/albumin ratio (CAR) and the neutrophil/lymphocyte ratio (NLR) for mortality in patients hospitalized with the diagnosis of COVID-19. Material and methods. The patients, who were hospitalized for COVID-19 and whose CRP, albumin, neutrophil, and lymphocyte levels were documented within the first 24 hours after admission, were analyzed retrospectively. Patients were divided into survivors and non-survivors; the groups were compared. Univariate and multivariate Cox regression models were developed to evaluate the CAR and the NLR as risk factors for mortality in COVID-19 patients. Results. One hundred and thirty patients were included in this study. The mean age of the survivor group (n=114) was 60±16 and 52% were male. The mean age of the non-survivor group (n=16) was 75±13 and 56% were male. In the non-survivor group, the CAR detected at the time of admission to the hospital was significantly higher compared to patients in the survivor group (p=0.026). Conclusion. As a result, the CAR, the NLR and LDH are independent risk factor indicators of mortality in hospitalized patients

Prognosis for local radical treatment in patients with esophageal squamous cell carcinoma with low-risk oligometastatic recurrence after curative resection: a retrospective cohort study.

Patients with esophageal carcinoma (EC) with recurrent disease have a poor prognosis. A limited numbers of metastases, safely treatable with curative intent, diagnosed after curative esophagectomy may be defined as oligometastatic recurrence (OLR). However, the appropriate number of metastases and metastatic organs involved remains incompletely characterized. And the role of local therapy in OLR after radical esophagectomy remains unknown. Therefore, this study aimed to more accurately define low-risk OLR in patients with esophageal squamous cell carcinoma (ESCC) treated with radical resection and investigate the role of chemotherapy combined with local treatment (CCLT) in these patients. A total of 83 sequential patients with ESCC who underwent radical esophagectomy, with an Eastern Cooperative Oncology Group (ECOG) performance status ≤2, with ability to tolerate chemotherapy (CT) and local treatment, and with newly diagnosed recurrence between January 2010 and May 2019 in our hospital were recruited. Overall survival (OS) curves after recurrence were analyzed using the Kaplan-Meier method, and a log-rank test was used to assess the OS differences. Cox proportional hazards regression analysis was performed to identify independent factors associated with 2-year OS. Regular follow-up examinations were assessed by thoracic and upper abdominal computed tomography (CT) scanning every 3 months in the first year, every 6 months over the next 2 years, and yearly thereafter. Of the 83 patients with ESCC (71 males and 12 females), the median age was 56 years (range, 37-79 years). Thirty-five patients with ESCC with ≤5 metastases safely treatable with curative intent located in a single organ had a favorable OS compared to 48 patients with metastases located in 2-3 organs with or without regional recurrence and/or regional lymph node (LN) metastases. In our study, low-risk OLR was defined as the presence of ≤5 metastases safely treatable with curative intent in a single organ and was compared to patients with 2-3 organs involved. The 2-year OS of patients with low-risk OLR with liver oligometastases was significantly worse than survival in patients with lung oligometastases (0% vs. 61.1%, P=0.009). Patients with ESCC in the low-risk OLR group treated with CCLT had a better 2-year OS after recurrence than those who received CT alone (66.7% vs. 30.4%, P=0.003). The multivariable Cox regression model identified treatment method [hazard ratio (HR) 3.920, P=0.02] as an independent factor affecting OS after recurrence for low-risk OLR. Low-risk OLR was defined as ≤5 metastases safely treatable with curative intent in a single organ. Patients with ESCC with low-risk OLR after curative resection treated with CCLT have a favorable OS compared to those treated with CT alone. CCLT is a promising treatment option for patients with ESCC and low-risk OLR.

Impact of Tumor Size and Differentiation Grade on Survival After Lobectomy and Segmentectomy for Patients with Early-Stage Lung Adenocarcinoma.

The purpose of this study was to investigate the effect of tumor size and differentiation grade on long term survival in patients with early-stage lung adenocarcinoma (LUAD) after lobectomy and segmentectomy. Patients with stage T1-2N0M0 LUAD who underwent lobectomy and segmentectomy were identified from the Surveillance, Epidemiology, and End Results database. Patients were stratified as grade I (well differentiated), grade II (moderately differentiated), and grade III/IV (poorly differentiated/undifferentiated) carcinomas. The effect of tumor size on overall survival (OS) and lung cancer-specific survival (LCSS) was evaluated using the multivariate Cox regression model, including the interaction between tumor size, type of surgery, and tumor differentiation grade. The inverse probability of treatment weighting method was used to adjust for bias between the groups. A total of 19,857 patients were identified, including 18,759 (94.4%) who underwent lobectomy and 1098 (5.5%) who underwent segmentectomy. A three-way interaction among tumor size, differentiation grade, and type of surgery was observed in the overall cohort. After stratifying by differentiation grade, plots of interaction revealed that lobectomy was associated with improved survival compared with segmentectomy when the tumor size exceeded 23 mm for grade I LUAD and 14 mm for grade II LUAD. No interaction was observed between the studied factors in grade III/IV carcinomas. This study interpreted the interaction between tumor size and type of surgery on long-term survival in patients with early stage LUAD and established a tumor size threshold beyond which lobectomy provided survival benefits compared with segmentectomy.

Effect of concomitant medications on treatment response and survival in non-metastatic castrate resistant prostate cancer: Exploratory analysis of the SPARTAN trial

BackgroundWe performed an exploratory analysis of the SPARTAN trial to determine whether concomitant exposure to several classes of commonly prescribed medications influenced the effect of apalutamide on overall survival (OS) and metastasis-free survival (MFS) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC). Patients and methodsSPARTAN was a phase III randomized controlled trial in which nmCRPC patients were randomly assigned in a 2:1 ratio to receive androgen deprivation therapy with or without apalutamide. We focused on 5 commonly prescribed classes of medications: metformin, statins, angiotensin converting enzyme inhibitors (ACEI), acetylsalicylic acid (ASA), and proton pump inhibitors (PPI) based on a plausible biological and clinical rationale. To determine the potential effect modification, we applied multivariable Cox regression models for OS and MFS separately with additional interaction terms. To determine the independent association of concomitant medications with OS and MFS, we used IPTW-based log-rank test. A 2-sided p < 0.01 was considered statistically significant. ResultsWe did not find statistically significant differences in effect from apalutamide on OS across subgroups stratified by concomitant exposure to any of the medication classes. While there was some difference in the treatment effect from apalutamide on MFS between patients with concomitant statins (adjusted hazard ratio [aHR]: 0.20; 95 % CI: 0.15–0.28) versus without concomitant statins (aHR: 0.31 [0.24–0.39]), this did not reach the pre-specified threshold of statistical significance (p = 0.011). On IPTW-based analysis, patients treated concomitantly with metformin (median: not reached versus 31 months; p = 0.002), or ACEI (median: 37 versus 29 months, p = 0.006) had significantly improved MFS. ConclusionsIn this post-hoc exploratory analysis of SPARTAN, effects of apalutamide on MFS and OS were consistent across subgroups stratified by exposure to concomitant medications. Exposure to concomitant metformin and ACEI was independently associated with a significant improvement in MFS.

Survival Patterns Based on First-site–specific Visceral Metastatic Prostate Cancer: Are Outcomes of Visceral Metastases the Same?

Background and objectiveVisceral metastatic disease in prostate cancer patients conveys a poor prognosis. Using advanced imaging techniques, studies have demonstrated increasing detection rates of visceral metastasis. Visceral metastases are now seen in up to 30–60% of prostate cancer patients. Survival patterns of site-specific visceral metastasis are described poorly in the literature. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. MethodsRetrospectively, we identified 203 prostate cancer patients with visceral metastases from the Mayo Clinic Advanced Prostate Cancer Registry. Patients were divided into three groups according to the first site of visceral metastases detected: lung, brain, or liver. Visceral metastases were detected primarily on either metabolic imaging (C-11 choline) or prostate-specific membrane antigen positron emission tomography computed tomography (CT) scan. Confirmation of visceral metastasis diagnosis was established with either biopsy when feasible or focused conventional imaging, including focused CT or magnetic resonance imaging. Overall survival and cancer-specific survival were estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression model was conducted to assess different variables that affect overall and cancer-specific survival. Key findings and limitationsOver a median (interquartile range) follow-up duration of 16.2 (3.9–49.8) mo, the overall and cancer-specific survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases than in patients with first-site brain or liver metastases (p < 0.0001). In univariate and multivariate analyses of factors impacting patients’ overall and cancer-specific survival, a high prostate-specific antigen level at diagnosis of visceral metastasis, concomitant bone and lymph node disease, and more than four visceral metastases were associated with poor overall and cancer-specific survival (p < 0.05). On the contrary, first-site lung metastasis was associated with improved overall and cancer-specific survival, compared with first-site liver and brain metastases (p < 0.001). Conclusions and clinical implicationsThese data suggest that prostate cancer patients with visceral metastatic disease have varying survival patterns according to first-site detected visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis. Patient summaryOur study explored the survival outcomes among patients with visceral metastatic prostate cancer employing cutting-edge imaging methods. Prostate cancer patients with metastases to different organs have different survival rates. Patients with cancer spreading to the lungs first showed better survival than those with cancer spreading to the brain or liver first.

Associations between early changes in the neutrophil-to-lymphocyte ratio after radical nephroureterectomy and treatment outcomes.

This study explored the impacts of peri-operative changes in the neutrophil-to-lymphocyte ratio (NLR) on the survival rate after radical nephroureterectomy. This retrospective analysis included a multicentric cohort of patients diagnosed with upper tract urothelial carcinoma (UTUC) who had undergone radical nephroureterectomy from 2012 to 2021. We assessed the preoperative NLR, postoperative NLR, delta-NLR (difference between postoperative and preoperative NLRs), and NLR change (ratio of postoperative to preoperative NLR). Additionally, patients were categorized according to increases in their preoperative and/or postoperative NLRs. Associations of survival with peri-operative changes in the NLR were investigated using Cox multivariate regression models. A total of 488 patients were included in the study, with a median age of 73years. Among the patients, 105 (21.5%) exhibited elevated preoperative and postoperative NLRs, 88 (18.0%) exhibited elevated preoperative NLR only, 53 (10.9%) exhibited elevated postoperative NLR only, and 242 (49.6%) exhibited normal NLRs. Multivariate analysis indicated significant negative correlations between both preoperative and postoperative increased NLRs and oncological outcomes, including nonurothelial tract recurrence-free survival and cancer-specific survival (hazard ratio [HR]: 1.65, P=0.017; HR: 2.12, P=0.014, respectively). This is the first study to evaluate the association between peri-operative changes in the NLR and the outcomes of patients with UTUC who underwent radical nephroureterectomy. Patients with elevated NLRs at both time points experienced considerably worse outcomes. Further research should explore whether increases in the NLR during long-term follow-up could indicate impending disease recurrence.

Outcomes of older adults with early-stage triple-negative breast cancer (TNBC) receiving chemotherapy: a single-institution experience.

Despite lower chemotherapy use in older triple-negative breast cancer (TNBC) patients, their outcomes match younger counterparts. We compared outcomes in early-stage TNBC patients by age receiving chemotherapy at a major cancer center with a national TNBC database. Retrospective study using institutional data on stage I-III TNBC (ER/PR < 10%) women with neoadjuvant/adjuvant chemotherapy. Based on their ages at diagnosis, patients were stratified into four categories: ≤40, 41-59, 60-69, and ≥ 70 years. Demographic and clinical characteristics recorded included race, disease stage, ER/PR positivity, treatment regimen, lymphatic or vascular invasion (LVI), histologic grade, Ki-67 level, body mass index (BMI), and pathologic complete response (pCR) following neoadjuvant treatment and are summarized using descriptive statistics. The primary endpoints were overall survival (OS), disease-free survival (DFS), and distant disease-free survival (DDFS); all were estimated using the Kaplan-Meier method. Both univariate and multivariate(MV) Cox regressions were applied to evaluate the impact of important covariates on these time-to-event endpoints. Of the 2336 patients studied, 492 (21.1%) were ≤ 40 years old, 1239 (53.1%) were 41-59, 461 (19.7%) were 60-69, and 144 (6.2%) were ≥ 70. In the univariate regression model of OS/DFS/DDFS, age ≥ 70 was significantly associated with worse OS (p = 0.0217); other factors associated with worse OS were non-anthracycline-based chemotherapy, higher tumor stage, and neoadjuvant chemotherapy. The multivariate Cox regression model, adjusted for race and stage, showed no significant effects of age on OS; however, patients ≥ 70 years old who received non-anthracycline treatment combinations had worse DFS (hazard ratio = 0.349 vs. 1.049, p = 0.0293) and DDFS (hazard ratio = 0.317 vs. 1.016, p = 0.0251) than patients ≤ 40 years old. DFS from MV model after adjusting for age, race, and disease stage, the hazard ratio between anthracycline + taxane treatments and anthracycline + other treatments in patients ≥ 70 years old was statistically significantly lower than in patients ≤ 40 years old (hazard ratios [HRs] = 0.349 vs. 1.049, p = 0.0293). Our findings indicate that outcomes such as DFS are less favorable in older compared to younger patients with early-stage TNBC, primarily in those who did not receive an anthracycline based chemotherapy regimen.

Association of potentially inappropriate medications with prognosis among older patients with non-small cell lung cancer

BackgroundPotentially inappropriate medications (PIMs) are common among older adults with cancer, but their association with overall survival (OS) among non-small cell lung cancer (NSCLC) patients remains unclear. This study aimed to investigate the association between the use of PIMs and OS in patients with NSCLC.MethodsIn this cohort study, we included patients ≥ 65 years with newly diagnosed NSCLC from January 2014 to December 2020. Potentially inappropriate medication (PIM) is defined by the Beers criteria of 2019 at baseline and within six months following the initiation of systemic therapy. Multivariable Cox regression model was built to assess the association between PIMs and overall survival (OS).ResultsWe finally included 338 patients with a median follow-up for OS of 1777 days. The prevalence of patients receiving at least one PIM was 39.9% (135/338) and 61.2% (71/116) at baseline and after systemic therapy, respectively. The most important factor associated with PIM use was the number of prescribed medications (P < 0.001). Baseline PIM use and PIM after systemic therapy were significantly associated with inferior OS (476 days vs. 844 days, P = 0.044; and 633 days vs. 1600 days, P = 0.007; respectively). In multivariable analysis, both baseline PIM use and PIM after systemic therapy were independent predictors of poor prognosis (adjusted HR, 1.33; 95% CI, 1.01–1.75; P = 0.041; and adjusted HR, 1.86; 95% CI, 1.11–3.14; P = 0.020; respectively).ConclusionsPIMs are prevalent among older patients with NSCLC and are independent predictors of NSCLC prognosis. There is an urgent need for clinicians to conduct medication reconciliation and appropriate deprescribing for this population, especially for patients with multiple PIMs.