Prediction of post-ESD esophageal stricture by a nomogram and risk factor analysis of ineffective oral steroids prophylaxis.

BACKGROUND AND AIMS: Several risk models for esophageal stricture after endoscopic submucosal dissection have been developed. However, some of them did not include the use of steroids in the risk analysis. Glucocorticoid sensitivity mediated by glucocorticoid receptor expression has not been discussed in this condition. METHODS: Clinical and endoscopic characteristics were included in the logistic regression model to establish a nomogram for stenosis prediction. The score for each risk factor was estimated. Risk factors of ineffective oral steroid prophylaxis were analyzed and glucocorticoid receptor expressions were detected by immunohistochemistry. RESULTS: Three hundred fourteen patients of endoscopic submucosal dissection for esophageal superficial neoplasms were included to develop the nomogram. The circumferential range(≤ 3/4, 3/4-1 or the whole circumference), longitudinal diameter reached 4 cm (yes or not) and lesion location (the cervical and upper thoracic part, the middle thoracic part or the lower thoracic part) consisted of the nomogram. Patients have a high risk of esophageal stricture if they have a total point greater than 36. In the simplified risk score model, the corresponding cutoff score was 1. 92 patients with oral steroid prophylaxis were separately analyzed and the circumferential mucosal defect involving 7/8 or more was an independent risk factor of ineffective prevention (OR 12.2, 95%CI 5.27-28.11). The expression of glucocorticoid receptor ß was higher in the stricture group (p = 0.042 for AOD; p = 0.016 for the scoring system). CONCLUSIONS: We established a nomogram for esophageal stricture prediction. Depending on the characteristics of lesions, it is possible to estimate the risk of stricture under routine post-ESD treatments (no steroids or oral steroids). Alternative treatments should be considered if the risk is extremely high, especially for patients with mucosal defects involving 7/8 or more of circumference in which oral steroid treatment tends to be ineffective. The higher glucocorticoid receptor ß may indicate potential glucocorticoid resistance.

Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using SEER database.

This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) to identify primary lung cancers with DM at presentation (M1). Kaplan-Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468-0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505-0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases.

Lower mortality risk associated with remdesivir + dexamethasone versus dexamethasone alone for the treatment of patients hospitalized for COVID-19.

BACKGROUND: Treatment guidelines were developed early in the pandemic when much about COVID-19 was unknown. Given the evolution of SARS-CoV-2, real-world data can provide clinicians with updated information. The objective of this analysis was to assess mortality risk in patients hospitalized for COVID-19 during the Omicron period receiving remdesivir+dexamethasone versus dexamethasone alone. METHODS: A large, multicenter US hospital database was used to identify hospitalized adult patients, with a primary discharge diagnosis of COVID-19 also flagged as "present on admission" treated with remdesivir+dexamethasone or dexamethasone alone from December 2021 to April 2023. Patients were matched 1:1 using propensity score matching and stratified by baseline oxygen requirements. Cox proportional hazards model was used to assess time to 14- and 28-day in-hospital all-cause mortality. RESULTS: A total of 33 037 patients were matched, with most patients ≥65 years old (72%), White (78%), and non-Hispanic (84%). Remdesivir+dexamethasone was associated with lower mortality risk versus dexamethasone alone across all baseline oxygen requirements at 14 days (no supplemental oxygen charges: adjusted hazard ratio [95% CI]: 0.79 [0.72-0.87], low flow oxygen: 0.70 [0.64-0.77], high flow oxygen/non-invasive ventilation: 0.69 [0.62-0.76], invasive mechanical ventilation/extracorporeal membrane oxygen (IMV/ECMO): 0.78 [0.64-0.94]), with similar results at 28 days. CONCLUSIONS: Remdesivir+dexamethasone was associated with a significant reduction in 14- and 28-day mortality compared to dexamethasone alone in patients hospitalized for COVID-19 across all levels of baseline respiratory support, including IMV/ECMO. However, the use of remdesivir+dexamethasone still has low clinical practice uptake. In addition, these data suggest a need to update the existing guidelines.

[Maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation in relation to offspring ventricular septal defects]. / 母亲MTRåŸºå› å¤šæ€æ€§åŠå ¶ä¸Žå›´å­•æœŸå¶é ¸è¡¥å çš„äº¤äº’ä½œç”¨ä¸Žå­ä»£å®¤é—´éš”ç¼ºæŸçš„å ³è”ç ”ç©¶.

OBJECTIVES: To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects (VSD) in offspring. METHODS: A case-control study was conducted, recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants. A questionnaire survey collected data on maternal exposures, and blood samples were analyzed for genetic polymorphisms. Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD. Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake. RESULTS: The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD (P<0.05). The GC and CC genotypes at rs3768139, AG and GG at rs1050993, AT and TT at rs4659743, GG at rs3768142, and GT and TT at rs3820571 were associated with a decreased risk of VSD (P<0.05). The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD (P<0.05). CONCLUSIONS: Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring. Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period, suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.

Propensity Score Analysis With Baseline and Follow-Up Measurements of the Outcome Variable.

A common feature in cohort studies is when there is a baseline measurement of the continuous follow-up or outcome variable. Common examples include baseline measurements of physiological characteristics such as blood pressure or heart rate in studies where the outcome is post-baseline measurement of the same variable. Methods incorporating the propensity score are increasingly being used to estimate the effects of treatments using observational studies. We examined six methods for incorporating the baseline value of the follow-up variable when using propensity score matching or weighting. These methods differed according to whether the baseline value of the follow-up variable was included or excluded from the propensity score model, whether subsequent regression adjustment was conducted in the matched or weighted sample to adjust for the baseline value of the follow-up variable, and whether the analysis estimated the effect of treatment on the follow-up variable or on the change from baseline. We used Monte Carlo simulations with 750 scenarios. While no analytic method had uniformly superior performance, we provide the following recommendations: first, when using weighting and the ATE is the target estimand, use an augmented inverse probability weighted estimator or include the baseline value of the follow-up variable in the propensity score model and subsequently adjust for the baseline value of the follow-up variable in a regression model. Second, when the ATT is the target estimand, regardless of whether using weighting or matching, analyze change from baseline using a propensity score that excludes the baseline value of the follow-up variable.

Survival Outcome Superiority of Total Pharyngolaryngectomy Compared with Chemoradiotherapy for T4aM0 Hypopharyngeal Squamous Cell Carcinoma: A Nationwide Database Study of Japan.

BACKGROUND: The purpose of this study is to elucidate whether total pharyngolaryngectomy (TPL) or chemoradiotherapy (CRT) provides a better prognostic outcome in patients with T4aM0 hypopharyngeal carcinoma (HPSCC) using a nationwide database. METHODS: All data were obtained from the Head and Neck Cancer Registry of Japan, and information from patients who were newly diagnosed with T4aM0 HPSCC between 2011 and 2015 was extracted. The primary endpoint was disease-specific survival (DSS), and the secondary endpoint was overall survival (OS). The inverse probability of treatment weighting (IPTW) adjustments was used for survival analyses. RESULTS: Our cohort included 1143 patients. The TPL and CRT groups included 724 and 419 patients, respectively. Following IPTW adjustments, both the OS and DSS of the TPL group were significantly longer than those of the CRT group (P = .02 and P = .002, respectively). CONCLUSIONS: Survival superiority was demonstrated for patients with T4aM0 HPSCC treated with TPL compared with those treated with CRT.

Incidence of hearing loss following COVID-19 among young adults in South Korea: a nationwide cohort study.

Background: The association of COVID-19 with hearing loss (HL) is unclear among young adults and needs to be investigated. This study was conducted to determine the association of COVID-19 with HL and sudden sensorineural hearing loss (SSNHL) in young adults. Methods: This nationwide population-based cohort study used data from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service. The study population consisted of young adult citizens aged 20-39 years without a history of HL. All participants were followed up from July 1, 2022 until HL, death, or December 31, 2022. A positive diagnosis of SARS-CoV-2 infection was determined through laboratory testing employing real-time reverse transcription polymerase chain reaction assays using nasopharyngeal or oropharyngeal swabs. The primary and secondary outcomes were HL and SSNHL, respectively. Age, sex, household income, Charlson comorbidity index, COVID-19 vaccination, hypertension, diabetes, and dyslipidemia-adjusted subdistribution hazard ratios (aSHRs) and 95% confidence intervals (CIs) were evaluated using the Fine-Gray subdistribution hazard regression model, considering overall death as a competing event to compare the aSHRs between COVID-19 positive and negative groups. Findings: A total of 6,716,879 young adults were eligible for the analyses. During 40,260,757 person-months (PMs) of follow-up, 38,269 cases of HL and 5908 cases of SSNHL were identified. The risk of HL (incidence: 11.9 versus 3.4/10,000 PMs; SHR, 3.51; 95% CI, 3.39-3.63; aSHR, 3.44; 95% CI, 3.33-3.56; P < 0.0001) and SSNHL (incidence: 1.8 versus 0.5/10,000 PMs; SHR, 3.58; 95% CI, 3.29-3.90; aSHR, 3.52; 95% CI, 3.23-3.83; P < 0.0001) was higher in COVID-19 group as compared to no COVID-19 group. In the sensitivity analyses that evaluated HL and SSNHL risks after adopting multiple imputations, utilizing inverse probability of treatment weighting, limiting study population to the cohort with a health screening examination, the results were consistent to the primary analysis. Interpretation: Our findings suggest a heightened risk of HL and SSNHL following COVID-19 in young adults. Due to study limitations, including the lack of objective audiological data, issues with generalizability to other populations, and the retrospective design, careful interpretation is necessary. Further studies with objective audiological data and a longer follow-up period are warranted. Funding: IITP (Institute for Information & Communications Technology Planning & Evaluation; IITP-2024- RS-00156439) and Jeju National University Hospital Research Fund (2023).

Adjustment for imbalances in baseline characteristics in the MAGNITUDE phase 3 study confirms the clinical benefit of niraparib in combination with abiraterone acetate plus prednisone in patients with metastatic prostate cancer.

BACKGROUND: MAGNITUDE (NCT03748641) demonstrated favourable outcomes with niraparib plus abiraterone acetate plus prednisone (+AAP) versus placebo+AAP in patients with BRCA1/2-altered metastatic castration-resistant prostate cancer (mCRPC). Imbalances in prognostic variables were reported between arms, which impacts estimation of both the clinical benefit and cost­effectiveness of niraparib+AAP for healthcare systems. A pre-specified multivariable analysis (MVA) demonstrated improved overall survival (OS) with niraparib+AAP. Here, we used an inverse probability of treatment weighting (IPTW) model to adjust for covariate imbalances and assess time-to-event outcomes. METHODS: IPTW analysis of time-to-event outcomes was conducted using data from patients with BRCA1/2-altered mCRPC (N = 225) in MAGNITUDE. Patients received niraparib+AAP or placebo+AAP. OS, radiographic progression-free survival, time to symptomatic progression, time to initiation of cytotoxic chemotherapy and time to prostate-specific antigen progression were assessed. Weighted Kaplan-Meier curves were generated for each endpoint, and adjusted hazard ratios (HR) were obtained from a weighted Cox model. RESULTS: Improvements in survival outcomes were estimated for niraparib+AAP versus placebo+AAP: unadjusted median OS was 30.4 months versus 28.6 months, respectively (HR: 0.79; 95 % confidence interval [CI]: 0.55, 1.12; p = 0.183). Following IPTW, median OS increased to 34.1 months with niraparib+AAP versus a decrease to 27.4 with placebo (HR: 0.65; 95 % CI: 0.46, 0.93; p = 0.017). Similar improvements were observed for other time-to-event endpoints. CONCLUSIONS: IPTW adjustment provided a more precise estimate of the clinical benefit of niraparib+AAP versus placebo+AAP in patients with BRCA1/2-altered mCRPC. Results were consistent with the pre-specified MVA, and further demonstrated the value of adjusting for baseline imbalances, particularly in smaller studies. TRIAL REGISTRATION: NCT03748641 (MAGNITUDE).

Effectiveness of pudendal nerve block in the management of acute post-haemorrhoidectomy pain in Asian individuals using inverse probability of treatment weighting (IPTW).

BACKGROUND: Inadequate management of acute post-haemorrhoidectomy pain is a major concern. Optimal pain management is necessary to reduce acute postoperative pain and improve care quality. Therefore, we investigated the efficacy of postoperative pudendal nerve block (PNB) in reducing acute post-haemorrhoidectomy pain in Asian individuals. METHODS: This retrospective cohort study analysed 108 adult patients with grade 3 haemorrhoids. Patients with anorectal cancer were excluded from this study. Among the 108 patients, 79 and 29 received spinal anaesthesia (SA) with PNB (SAPNB) and SA alone, respectively. Propensity score matching and inverse probability of treatment weighting were performed to adjust for the effects of confounders. RESULTS: Patients receiving SAPNB had significantly lower postoperative pain scores 6, 12, and 18 h after haemorrhoidectomy but significantly higher postoperative pain scores 24 and 48 h after haemorrhoidectomy than did patients receiving SA alone. PNB, older age, female sex, reduced operation time, and absence of cardiovascular disease reduced the risk of moderate to severe postoperative pain. Only the addition of PNB was consistently associated with a reduced risk of moderate to severe pain 6, 12, and 18 h after haemorrhoidectomy. Patients receiving SAPNB had significantly lower risks of perianal swelling and urinary retention but a significantly higher risk of nausea than did those receiving SA alone. The two groups exhibited similarity in their rates of postoperative readmission because of poor pain management and their lengths of stay upon readmission. CONCLUSION: The addition of PNB to SA may effectively reduce acute post-haemorrhoidectomy pain.

Sex-specific associations between habitual snoring and cancer prevalence: insights from a US Cohort Study.

Study Objectives: To investigate the sex-specific association between habitual snoring and overall cancer prevalence and subtypes, and to examine the influence of age, body mass index (BMI), and sleep duration on this association. Methods: This study utilized data from the National Health and Nutrition Examination Survey cycles between 2005 and 2020 and included 15 892 participants aged 18 and over. We employed inverse probability of treatment weighting based on propensity scores to adjust for confounders when comparing the prevalence of cancer between habitual snorers and non-habitual snorers for each sex and cancer type. Subgroup analyses were conducted based on sleep duration, age, and BMI categories. Results: The cohort (mean age 48.2 years, 50.4% female, and 30.5% habitual snorers) reported 1385 cancer cases. In men, habitual snoring was linked to 26% lower odds of any cancer (OR 0.74, 95% CI: 0.66 to 0.83), while in women, it showed no significant difference except lower odds of breast cancer (OR 0.77, 95% CI: 0.63 to 0.94) and higher odds of cervix cancer (OR 1.54, 95% CI: 1.18 to 2.01). Age and sleep duration significantly influenced the snoring-cancer relationship, with notable variations by cancer type and sex. Conclusions: Habitual snoring exhibits sex-specific associations with cancer prevalence, showing lower prevalence in men and varied results in women. These findings emphasize the critical need for further research to uncover the biological mechanisms involved. Future investigations should consider integrating sleep characteristics with cancer prevention and screening strategies, focusing on longitudinal research and the integration of genetic and biomarker analyses to fully understand these complex relationships.

Reduction in the need for surgery and mortality after early administration of fibrinolytics following empyema drainage.

OBJECTIVES: Although intrapleural administration of fibrinolytics is an important treatment option for the management of empyema, the addition of fibrinolytics failed to reduce the need for surgery and mortality in previous randomized controlled trials. This study aimed to investigate the effects of administrating fibrinolytics in the early phase (within 3 days of chest tube insertion) of empyema compared with late administration or no administration. METHODS: We used the Japanese Diagnosis Procedure Combination Inpatient Database to identify patients aged ≥16 years who were hospitalized and underwent chest tube drainage for empyema. A 1:2 propensity score matching and stabilized inverse probability of treatment weighting were conducted. RESULTS: Among the 16 265 eligible patients, 3082 and 13 183 patients were categorized into the early and control group, respectively. The proportion of patients who underwent surgery was significantly lower in the early fibrinolytics group than in the control group; the odds ratio (95% confidence interval) was 0.69 (0.54-0.88) in the propensity score matching (P = 0.003) and 0.64 (0.50-0.80) in the stabilized inverse probability of treatment weighting analysis (P < 0.001). All-cause 30-day in-hospital mortality, length of hospital stay, duration of chest tube drainage, and total hospitalization costs were also more favourable in the early fibrinolytics group. CONCLUSIONS: The early administration of fibrinolytics may reduce the need for surgery and death in adult patients with empyema.

PA-MSHA improves prognosis of patients undergoing radical cystectomy: a retrospective cohort study using inverse probability of treatment weighting.

Objective: To observe the effect of Pseudomonas aeruginosa mannose-sensitive hemagglutinin (PA-MSHA) on the prognosis and the incidence of lymphatic leakage in patients undergoing radical cystectomy (RC). Method: A total of 129 patients who underwent RC in Lanzhou University Second Hospital from 2013 to 2022 were enrolled in this study. They were divided into 43 patients treated with PA-MSHA and 86 patients in the control group. Inverse probability of treatment weighting (IPTW) was applied to reduce potential selection bias. Kaplan-Meier method and Cox regression analysis were used to analyze the effect of PA-MSHA on the survival of patients and the incidence of postoperative lymphatic leakage. Results: The PA-MSHA group exhibited improved overall survival (OS) and cancer-specific survival (CSS) rates compared to the control group. The 3-year and 5-year overall survival (OS) rates for the PA-MSHA group were 69.1% and 53.2%, respectively, compared to 55.6% and 45.3% for the control group (Log-rank=3.218, P=0.072). The 3-year and 5-year cancer-specific survival (CSS) rates for the PA-MSHA group were 73.3% and 56.5%, respectively, compared to 58.0% and 47.3% for the control group (Log-rank=3.218, P=0.072). Additionally, the 3-year and 5-year progression-free survival (PFS) rates for the PA-MSHA group were 74.4% and 56.8%, respectively, compared to 57.1% and 52.2% for the control group (Log-rank=2.016, P=0.156). Multivariate Cox regression analysis indicates that lymph node metastasis and distant metastasis are poor prognostic factors for patients, while the use of PA-MSHA can improve patients' OS (HR: 0.547, 95%CI: 0.304-0.983, P=0.044), PFS (HR: 0.469, 95%CI: 0.229-0.959, P=0.038) and CSS (HR: 0.484, 95%CI: 0.257-0.908, P=0.024). The same trend was observed in the cohort After IPTW adjustment. Although there was no significant difference in the incidence of postoperative lymphatic leakage [18.6% (8/35) vs. 15.1% (84.9%), P=0.613] and pelvic drainage volume [470 (440) ml vs. 462.5 (430) ml, P=0.814] between PA-MSHA group and control group, PA-MSHA could shorten the median retention time of drainage tube (7.0 d vs 9.0 d) (P=0.021). Conclusion: PA-MSHA may improve radical cystectomy in patients with OS, PFS, and CSS, shorten the pelvic drainage tube retention time.

Evaluation and comparison of covariate balance metrics in studies with time-dependent confounding.

Marginal structural models have been increasingly used by analysts in recent years to account for confounding bias in studies with time-varying treatments. The parameters of these models are often estimated using inverse probability of treatment weighting. To ensure that the estimated weights adequately control confounding, it is possible to check for residual imbalance between treatment groups in the weighted data. Several balance metrics have been developed and compared in the cross-sectional case but have not yet been evaluated and compared in longitudinal studies with time-varying treatment. We have first extended the definition of several balance metrics to the case of a time-varying treatment, with or without censoring. We then compared the performance of these balance metrics in a simulation study by assessing the strength of the association between their estimated level of imbalance and bias. We found that the Mahalanobis balance performed best. Finally, the method was illustrated for estimating the cumulative effect of statins exposure over one year on the risk of cardiovascular disease or death in people aged 65 and over in population-wide administrative data. This illustration confirms the feasibility of employing our proposed metrics in large databases with multiple time-points.

Propensity weighting plus adjustment in proportional hazards model is not doubly robust.

Recently, it has become common for applied works to combine commonly used survival analysis modeling methods, such as the multivariable Cox model and propensity score weighting, with the intention of forming a doubly robust estimator of an exposure effect hazard ratio that is unbiased in large samples when either the Cox model or the propensity score model is correctly specified. This combination does not, in general, produce a doubly robust estimator, even after regression standardization, when there is truly a causal effect. We demonstrate via simulation this lack of double robustness for the semiparametric Cox model, the Weibull proportional hazards model, and a simple proportional hazards flexible parametric model, with both the latter models fit via maximum likelihood. We provide a novel proof that the combination of propensity score weighting and a proportional hazards survival model, fit either via full or partial likelihood, is consistent under the null of no causal effect of the exposure on the outcome under particular censoring mechanisms if either the propensity score or the outcome model is correctly specified and contains all confounders. Given our results suggesting that double robustness only exists under the null, we outline 2 simple alternative estimators that are doubly robust for the survival difference at a given time point (in the above sense), provided the censoring mechanism can be correctly modeled, and one doubly robust method of estimation for the full survival curve. We provide R code to use these estimators for estimation and inference in the supporting information.

Final analyses of the prospective controlled trial on the efficacy of uracil and tegafur/leucovorin as an adjuvant treatment for stage II colon cancer with risk factors for recurrence using propensity score-based methods (JFMC46-1201).

BACKGROUND: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. Using propensity score matching, we previously reported that the 3-year disease-free survival (DFS) rate was significantly higher in patients treated with uracil and tegafur plus leucovorin (UFT/LV) against surgery alone. We report the final results, including updated 5-year overall survival (OS) rates and risk factor analysis outcomes. METHODS: In total, 1902 high-risk stage II CC patients with T4, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, and/or < 12 dissected lymph nodes were enrolled in this prospective, non-randomized controlled study based on their self-selected treatment. Oral UFT/LV therapy was administered for six months after surgery. RESULTS: Of the 1880 eligible patients, 402 in Group A (surgery alone) and 804 in Group B (UFT/LV) were propensity score-matched. The 5-year DFS rate was significantly higher in Group B than in Group A (P = 0.0008). The 5-year OS rates were not significantly different between groups. The inverse probability of treatment weighting revealed significantly higher 5-year DFS (P = 0.0006) and 5-year OS (P = 0.0122) rates in group B than in group A. Multivariate analyses revealed that male sex, age ≥ 70 years, T4, < 12 dissected lymph nodes, and no adjuvant chemotherapy were significant risk factors for DFS and/or OS. CONCLUSION: The follow-up data from our prospective non-randomized controlled study revealed a considerable survival advantage in DFS offered by adjuvant chemotherapy with UFT/LV administered for six months over surgery alone in individuals with high-risk stage II CC. TRIAL REGISTRATION: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019), UMIN Clinical Trials Registry: UMIN000007783 (date of registration: 18/04/2012).

Surgical management of the aortic root in acute type A aortic dissection: A comparative analysis.

BACKGROUND: This study aimed to assess the early- and mid-term outcomes of aortic root repair and replacement, and to provide evidence to improve root management in acute type A aortic dissection (AAAD). METHODS: This study enrolled 455 patients who underwent AAAD root repair (n = 307) or replacement (n = 148) between January 2016 and December 2017. Inverse probability of treatment weighting (IPTW) method was used to control for treatment selection bias. The primary outcomes were in-hospital mortality, mid-term survival, and proximal aortic reintervention. RESULTS: The success rate of root repair was 99.7%. The in-hospital mortality in the conservative root repair (CRR) and aggressive root replacement (ARR) were 8.1% and 10.8%. The median follow-up time was 67.76 months (IQR, 67-72 months). After adjusting for baseline factors, there was no significant differences in mid-term survival (p = .750) or the proximal aortic reintervention rate (p = .550) between the two groups. According to Cox analysis, age, hypertension, severe aortic regurgitation, CPB time, and concomitant CABG were all factors associated with mid-term mortality. Regarding reintervention, multivariate analysis identified renal insufficiency, bicuspid aortic valve, root diameter ≥ 45 mm, and severe aortic regurgitation as risk factors, while CRR did not increase the risk of reintervention. The subgroup analysis revealed heterogeneity in the effects of surgical treatment across diverse populations based on a variety of risk factors. CONCLUSIONS: For patients with AAAD, both CRR and ARR are appropriate operations with promising early and mid-term outcomes. The effects of treatment show heterogeneity across diverse populations based on various risk factors.

Exploring Differences in Intraoperative Medication Use Between African American and Non-Hispanic White Patients During General Anesthesia: Retrospective Observational Cohort Study.

This study aimed to explore whether differences exist in anesthesia care providers' use of intraoperative medication between African American and non-Hispanic White patients in adult surgical patients who underwent noncardiothoracic nonobstetric surgeries with general anesthesia. A retrospective observational cohort study used electronic health records between January 1, 2018 and August 31, 2019 at a large academic health system in the southeastern United States. To evaluate the isolated impact of race on intraoperative medication use, inverse probability of treatment weighting using the propensity scores was used to balance the covariates between African American and non-Hispanic White patients. Regression analyses were then performed to evaluate the impact of race on the total dose of opioid analgesia administered, and the use of midazolam, sugammadex, antihypotensive drugs, and antihypertensive drugs. Of the 31,790 patients included in the sample, 58.9% were non-Hispanic Whites and 13.6% were African American patients. After adjusting for significant covariates, African American patients were more likely to receive midazolam premedication (p < .0001; adjusted odds ratio [aOR] = 1.17, 99.9% CI [1.06, 1.30]), and antihypertensive drugs (p = .0002; aOR = 1.15, 99.9% CI [1.02, 1.30]), and less likely to receive antihypotensive drugs (p < .0001; aOR = 0.85, 99.9% CI [0.76, 0.95]) than non-Hispanic White patients. However, we did not find significant differences in the total dose of opioid analgesia administered, or sugammadex. This study identified differences in intraoperative anesthesia care delivery between African American and non-Hispanic White patients; however, future research is needed to understand mechanisms that contribute to these differences and whether these differences are associated with patient outcomes.

Elevated cortical blood flow insufficiency volume as a predictor of adverse outcomes in aneurysmal subarachnoid hemorrhage: a large prospective quantitative computed tomography perfusion study.

PURPOSE: Early hypoperfusion changes exist in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to investigate a readily obtainable quantitative computed tomography perfusion (CTP) parameter that could assist in quickly identifying patients at risk of delayed cerebral ischemia (DCI) and poor 90-day functional outcomes on admission. METHODS: We prospectively collected data between 2021.04 and 2022.12. Preoperative CTP data were post-processed using RAPID software. The cortical blood flow insufficiency (CBFI) was defined as Time-to-maximum > 4.0 s. Patients were categorized into four groups according to CBFI volume distribution. To minimize differences among the groups, we employed stabilized inverse probability of treatment weighting (sIPTW). The primary outcome was DCI and poor 90-day functional outcomes (modified Rankin Scale, 3-6) was the secondary outcome. Multivariable Cox or Logistic analysis were performed to estimate the association between CBFI volume and the study outcomes, both before and after sIPTW. RESULTS: At baseline, the mean (SD) age of the 493 participants was 55.0 (11.8) years, and 299 (60.6%) were female. One hundred and seven participants with DCI and eighty-six participants with poor 90-day functional outcomes were identified. After sIPTW, CBFI volume demonstrated a significant association with DCI (Cox regression: Group 4 versus Group 1, HR 3.69, 95% CI 1.84-7.01) and poor 90-day functional outcomes (Logistic regression: Group 4 versus Group 1, OR 4.61, 95% CI 2.01-12.50). CONCLUSION: In this study, an elevated preoperative CBFI volume was associated with adverse outcomes in aSAH patients. More well-designed studies are needed to confirm this association.

The performance of marginal structural models for estimating risk differences and relative risks using weighted univariate generalized linear models.

We used Monte Carlo simulations to compare the performance of marginal structural models (MSMs) based on weighted univariate generalized linear models (GLMs) to estimate risk differences and relative risks for binary outcomes in observational studies. We considered four different sets of weights based on the propensity score: inverse probability of treatment weights with the average treatment effect as the target estimand, weights for estimating the average treatment effect in the treated, matching weights and overlap weights. We considered sample sizes ranging from 500 to 10,000 and allowed the prevalence of treatment to range from 0.1 to 0.9. We examined both the robust variance estimator when using generalized estimating equations with an independent working correlation matrix and a bootstrap variance estimator for estimating the standard error of the risk difference and the log-relative risk. The performance of these methods was compared with that of direct weighting. Both the direct weighting approach and MSMs based on weighted univariate GLMs resulted in the identical estimates of risk differences and relative risks. When sample sizes were small to moderate, the use of an MSM with a bootstrap variance estimator tended to result in the most accurate estimates of standard errors. When sample sizes were large, the direct weighting approach and an MSM with a bootstrap variance estimator tended to produce estimates of standard error with similar accuracy. When using a MSM to estimate risk differences and relative risks, in general it is preferable to use a bootstrap variance estimator than the robust variance estimator. We illustrate the application of the different methods for estimating risks differences and relative risks using an observational study on the effect on mortality of discharge prescribing of a beta-blocker in patients hospitalized with acute myocardial infarction.

Treatment patterns and outcomes among adults with immune thrombocytopenia receiving pharmaceutical second-line therapies: a retrospective cohort study using administrative claims data.

OBJECTIVES: To describe and compare real-world treatment patterns and clinical outcomes among individuals with immune thrombocytopenia (ITP) receiving second-line therapies (rituximab, romiplostim, or eltrombopag). METHODS: A retrospective cohort study was conducted using a large administrative claims database (January 2013-May 2020) among continuously enrolled patients ≥18 years prescribed second-line ITP therapies. The index date was the date of the first claim of the study medications. Treatment patterns and outcomes were measured during the 12-month follow-up period. Inverse probability of treatment weighting (IPTW) was used to balance covariates across treatment groups. Multivariable logistic regression was used to compare treatment patterns and bleeding risk outcomes. RESULTS: A total of 695 patients were included (rituximab, N = 285; romiplostim, N = 212; eltrombopag, N = 198). After IPTW, all baseline covariates were balanced. Compared to eltrombopag, patients in the rituximab cohort were 57% more likely to receive other ITP therapies (systematic corticosteroids or third-line therapies) during the follow-up period (odds ratio [OR] = 1.571, p = .030). There was no significant difference in the odds of receiving a different second-line therapy or experiencing a bleeding-related episode among three groups (p > .050). Patients in the romiplostim cohort were 69% more likely to receive rescue therapy compared to those in the rituximab cohort (OR = 1.688, p = .025). CONCLUSION: Patients with ITP receiving rituximab were more likely to need other ITP therapies but did not experience higher risk of bleeding compared to those receiving eltrombopag or romiplostim. Benefits, risks, cost-effectiveness, and patient preference should all be considered in optimizing second-line therapy for ITP.