BACKGROUND: Comparative studies on surgical treatments with time-to-event endpoints have provided substantial evidence for clinical practice, but the accurate use of survival data analysis and the control of confounding bias remain big challenges.
METHODS: This was a survey of surgical studies with survival outcomes published in four general medical journals and five general surgical journals in 2021. The two most concerned statistical issues were evaluated, including confounding control by propensity score analysis (PSA) or multivariable analysis and testing of proportional hazards (PH) assumption in Cox model.
RESULTS: A total of 74 studies were included, comprising 63 observational studies and 11 randomized controlled trials. Among the observational studies, the proportion of studies utilizing PSA in surgical oncology and non-oncology studies was similar (40.9 % versus 36.8 %, P = 0.762). However, the former reported a significantly lower proportion of PH assumption assessments compared to the latter (13.6 % versus 42.1 %, P = 0.020). Twenty-five observational studies (25/63) used PSA methods, but two-thirds of them (17/25) showed unclear balance of baseline data after PSA. And the proportion of PH assumption testing after PSA was slightly lower than that before PSA, but the difference was not statistically significant (24.0 % versus 28.0 %, P = 0.317). Comprehensive suggestions were given on confounding control in survival analysis and alternative resolutions for non-compliance with PH assumption.
CONCLUSIONS: This study highlights suboptimal reporting of PH assumption evaluation in observational surgical studies both before and after PSA. Efforts and consensus are needed with respect to the underlying assumptions of statistical methods.

UNASSIGNED: The optimal regimen of infliximab salvage in acute severe ulcerative colitis (ASUC) patients remains controversial. This study aimed to compare accelerated and standard infliximab induction in Chinese ASUC patients, and to explore risk factors and concrete accelerated regimens for them.
UNASSIGNED: Data were retrospectively collected from steroid-refractory ASUC patients receiving infliximab as rescue therapy at seven tertiary centers across China. Outcomes including colectomy and clinical remission (Mayo score ≤ 2 and every subscore ≤ 1 at Day 14) rates were compared between patients receiving accelerated and standard infliximab induction using propensity score adjustment for potential confounders. The dose-response relationship was explored by plotting restricted cubic splines. Logistic regression and Cox proportional hazards regression analyses were performed to determine risk factors for adverse outcomes. A systematic review and meta-analysis was also performed.
UNASSIGNED: A total of 76 patients were analysed: 29 received standard and 47 received accelerated induction. The accelerated group had a higher 90-day colectomy rate (17.8% vs 0%, P = 0.019) and lower clinical remission rate (27.7% vs 65.5%, P = 0.001). After adjusting for propensity score and institution, there was no significant difference in colectomy or clinical remission rates (both P > 0.05). Dose-effect curves showed decreased colectomy hazard with higher cumulative infliximab dosage within 5 days, with no improvement observed for increasing cumulative infliximab dosage within 28 days. Multivariate logistic regression analyses revealed C-reactive protein of >10 mg/L at infliximab initiation (odds ratio = 5.00, 95% confidence interval: 1.27-24.34) as an independent risk factor for no clinical remission. Meta-analysis also revealed no significant difference in colectomy rates at 3 months (P = 0.54).
UNASSIGNED: After adjusting for confounders, there were no significant differences in colectomy or clinical remission rates between accelerated and standard infliximab induction among ASUC patients. Early administration of an intensified dosage within 5 days may be beneficial. Elevated C-reactive protein at infliximab initiation indicated need for intensive treatment.

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors.
METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance.
RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative.
CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.

BACKGROUND: Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown.
METHODS: We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone.
RESULTS: The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease.
CONCLUSIONS: Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

Objective  Our objective was to compare the long-term outcomes of endoscopic resection versus open surgery in combination with radiotherapy for locally advanced sinonasal malignancies (SNMs). Methods  Data for continuous patients with sinonasal squamous cell carcinoma and adenocarcinoma who received surgery (endoscopic or open surgery) combined with radiotherapy in our center between January 1999 and December 2016 were retrospectively reviewed. A 1:1 matching with propensity scores was performed. Overall survival (OS), progression-free survival (PFS), and local recurrence rate (LRR) were evaluated. Results  We identified 267 eligible patients, 90 of whom were included after matching: 45 patients in the endoscopy group and 45 in the open group. The median follow-up time was 87 months. In the endoscopic group, 84.4% of patients received intensity-modulated radiotherapy (IMRT), with a mean gross tumor volume (GTV) dose of 68.28 Gy; in the open surgery group, 64.4% of patients received IMRT, with a mean GTV dose of 64 Gy. The 5-year OS, PFS, and LRR were 69.9, 58.6, and 24.5% in the endoscopic group and 64.6, 54.4, and 31.8% in the open surgery group, respectively. Multivariable regression analysis revealed that the surgical approach was not associated with lower OS, PFS, or LRR. The overall postoperative complications were 13% in the endoscopic group, while 21.7% in the open group. Conclusion  For patients with locally advanced SNMs, minimally invasive endoscopic resection, in combination with a higher radiation dose and new radiation techniques such as IMRT, yields survival outcomes similar to those of open surgery in combination with radiotherapy.

UNASSIGNED: Red cell distribution width (RDW) and serum calcium (Ca) levels are predictors of in-hospital mortality in acute myocardial infarction (AMI) patients. However, their sensitivity and specificity are limited. Therefore, this study aimed to determine whether the RDW to Ca ratio (RCR) acquired on admission can be used to predict the in-hospital mortality of AMI patients.
UNASSIGNED: This retrospective cohort study extracted clinical information from the Medical Information Market for Intensive IV (MIMIC-IV) database on 2,910 AMI patients enrolled via propensity score matching (PSM). Prognostic values were assessed using a multivariate logistic model and three PSM approaches. Analysis was performed based on stratified variables and interactions among sex, age, ethnicity, anemia, renal disease, percutaneous transluminal coronary intervention (PCI), coronary artery bypass grafting (CABG), atrial fibrillation, congestive heart failure, dementia, diabetes, paraplegia, hypertension, cerebrovascular disease, and Sequential Organ Failure Assessment (SOFA) score.
UNASSIGNED: A total of 4,105 ICU-admitted AMI patients were analyzed. The optimal cut-off value of the RCR for in-hospital mortality was 1.685. The PSM was performed to identify 1,455 pairs (2,910) of score-matched patients, with balanced differences exhibited for nearly all variables.The patients\' median age was 72 years (range, 63-82 years) and 60.9% were male. The risk of in-hospital mortality incidence increased with increasing RCR levels. After adjusting for confounders, the risk ratio for the incidence of in-hospital mortality for high RCR was 1.75 [95% confidence interval (CI): 1.60-1.94, P = 0.0113] compared to that associated with low RCR in the PSM cohort. High RCR was also substantially implicated in in-hospital mortality incidence in the weighted cohorts [odds ratio (OR) = 1.76, 95% CI: 1.62-1.94, P = 0.0129]. Assessment of RCR in three groups showed that patients with high RCR also had a higher risk of in-hospital mortality (OR = 3.04; 95% CI, 2.22-4.16; P < 0.0001) than in patients with RCR in the adjusted model. In the sensitivity analysis, both the original and weighted groups showed similar results.
UNASSIGNED: The RCR at admission may be useful for predicting in-hospital mortality in ICU-admitted AMI patients.

The inverse probability of treatment weighting (IPTW) approach is commonly used in propensity score analysis to infer causal effects in regression models. Due to oversized IPTW weights and errors associated with propensity score estimation, the IPTW approach can underestimate the standard error of causal effect. To remediate this, bootstrap standard errors have been recommended to replace the IPTW standard error, but the ordinary bootstrap (OB) procedure might still result in underestimation of the standard error because of its inefficient resampling scheme and untreated oversized weights. In this paper, we develop a generalized bootstrap (GB) procedure for estimating the standard error and confidence intervals of the IPTW approach. Compared with the OB procedure and other three procedures in comparison, the GB procedure has the highest precision and yields conservative standard error estimates. As a result, the GB procedure produces short confidence intervals with highest coverage rates. We demonstrate the effectiveness of the GB procedure via two simulation studies and a dataset from the National Educational Longitudinal Study-1988 (NELS-88).

BACKGROUND: Bone metastases affect 50% to 70% of breast cancer (BC) patients and have a high mortality rate. Adipose tissue loss plays a pivotal role in the progression of cancer.
OBJECTIVE: This study aims to evaluate the prognostic value of adipose tissue for bone metastasis in BC patients.
METHODS: 517 BC patients were studied retrospectively. Patients\' characteristics before the surgery were collected. Quantitative measurements of the subcutaneous fat index (SFI) were performed at the level of the eleventh thoracic vertebra. In order to adjust for the heterogeneity between the low SFI and high SFI groups, propensity score matching (PSM) was used. The Kaplan-Meier method was used to estimate the 5-year bone metastatic incidence. The prognostic analysis was performed with the Cox regression models.
RESULTS: Compared with the patients without bone metastasis, the patients with bone metastasis had reduced SFI levels. In addition, Kaplan-Meier analysis revealed that patients with low SFI were more likely to develop bone metastases. The independent predictive value of SFI for bone metastases was confirmed by Cox regression analysis. The survival analysis was repeated after PSM with a 1:1 ratio, yielding similar results (P< 0.05).
CONCLUSIONS: SFI is an independent predictor of bone metastasis in BC patients.

Whether combination therapy has higher hemostatic efficacy than epinephrine injection monotherapy in different Forrest classifications is not clear. This study aimed to compare hemostatic efficacy between epinephrine injection monotherapy (MT) and combination therapy (CT) based on different Forrest classifications.
We retrospectively analyzed peptic ulcer bleeding (PUB) patients who underwent endoscopic epinephrine injections or epinephrine injections combined with a second therapy between March 2014 and June 2022 in our center, and the patients were divided into MT group or CT group. Subsequently, a propensity score matching analysis (PSM) was performed and rebleeding rates were calculated according to Forrest classifications via a stratified analysis.
Overall, 605 patients who met the inclusion criteria were included, and after PSM, 173 patients in each of the CT and MT groups were included. For PUB patients with nonbleeding visible vessels (FIIa), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 8.8%, 17.5%, 19.3%, and 19.3% in the MT group, respectively, and rates were 0%, 4.1%, 5.5%, and 5.5% in the CT group, respectively, with significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.015, P = 0.011, P = 0.014, and P = 0.014, respectively). However, for PUB patients with oozing bleeding (FIb), the rebleeding rates by Days 3, 7, 14, and 30 after PSM were 14.9%, 16.2%, 17.6%, and 17.6% in the MT group, respectively, and rates were 13.2%, 14.7%, 14.7%, and 16.2% in the CT group, respectively, with no significant differences observed between the two groups by Days 3, 7, 14, and 30 (P = 0.78, P = 0.804, P = 0.644 and P = 0.825).
Combined therapy has higher hemostatic efficacy than epinephrine injection monotherapy for PUB patients with visible blood vessel (FIIa) ulcers. However, epinephrine injection monotherapy is equally as effective as combined therapy for PUB patients with oozing blood (FIb) ulcers.

UNASSIGNED: To comprehensively assess and validate the associations between insulin-like growth factor 2 (IGF2) gene methylation in peripheral blood leukocytes (PBLs) and colorectal cancer (CRC) risk and prognosis.
UNASSIGNED: The association between IGF2 methylation in PBLs and CRC risk was initially evaluated in a case-control study and then validated in a nested case-control study and a twins\' case-control study, respectively. Meanwhile, an initial CRC patient cohort was used to assess the effect of IGF2 methylation on CRC prognosis and then the finding was validated in the EPIC-Italy CRC cohort and TCGA datasets. A propensity score (PS) analysis was performed to control for confounders, and extensive sensitivity analyses were performed to assess the robustness of our findings.
UNASSIGNED: PBL IGF2 hypermethylation was associated with an increased risk of CRC in the initial study (ORPS-adjusted, 2.57, 95% CI: 1.65 to 4.03, P<0.0001), and this association was validated using two independent external datasets (ORPS-adjusted, 2.21, 95% CI: 1.28 to 3.81, P=0.0042 and ORPS-adjusted, 10.65, 95% CI: 1.26 to 89.71, P=0.0295, respectively). CRC patients with IGF2 hypermethylation in PBLs had significantly improved overall survival compared to those patients with IGF2 hypomethylation (HRPS-adjusted, 0.47, 95% CI: 0.29 to 0.76, P=0.0019). The prognostic signature was also observed in the EPIC-Italy CRC cohort, although the HR did not reach statistical significance (HRPS-adjusted, 0.69, 95% CI: 0.37 to 1.27, P=0.2359).
UNASSIGNED: IGF2 hypermethylation may serve as a potential blood-based predictive biomarker for the identification of individuals at high risk of developing CRC and for CRC prognosis.