Inverse Treatment Research Articles

Effectiveness of Adalimumab Biosimilars and Originator for Psoriasis.

The uncertainties about the real-world effectiveness of adalimumab biosimilars limit their widespread adoption for psoriasis. To compare the effectiveness of adalimumab biosimilars Amjevita and Imraldi with Humira for psoriasis. An emulation of 2 targeted pragmatic clinical trials was conducted using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR), a prospective pharmacovigilance registry tracking individuals receiving biologic and conventional systemic treatments for psoriasis in the UK and the Republic of Ireland. Data from patients with psoriasis using adalimumab registered to BADBIR were included. Data were collected from September 2007 to January 2023, and data were analyzed from January to September 2023. The effectiveness of initiating Amjevita and Imraldi were compared with initiating Humira among adalimumab-naive patients, and the effectiveness of switching from Humira to either Amjevita or Imraldi were compared with continuing Humira among patients who had been using Humira consistently for more than 2 years. The study outcomes were absolute Psoriasis Area and Severity Index (PASI) score of 2 or less and PASI score of 4 or less at 12 months after the index date. Inverse propensity treatment weighting was used to analyze receiving either biosimilars or Humira to account for confounding. Multiple imputations were used to account for missing PASI data at 12 months and inverse probability of censoring weighting to account for censorship due to deviation from the treatments under investigation. Logistic regression models were fitted to compare the outcomes between study cohorts. Of 11 400 included patients, 6924 (60.7%) were male, and the mean (SD) age was 45.3 (12.5) years. A total of 6133 patients were identified in the new user analysis (5416 starting Humira, 382 starting Amjevita, and 335 starting Imraldi) and 5267 patients in the switcher analysis (3808 continuing Humira, 847 switching to Amjevita, and 612 switching to Imraldi). Amjevita and Imraldi new users had no significantly different probability of achieving a PASI score of 2 or less (Amjevita: adjusted odds ratio [aOR], 0.98; 95% CI, 0.78-1.25; Imraldi: aOR, 0.83; 95% CI, 0.64-1.07) and a PASI score of 4 or less (Amjevita: aOR, 1.07; 95% CI, 0.84-1.37; Imraldi: aOR, 0.91; 95% CI, 0.69-1.20) compared with Humira new users. Patients who switched to Amjevita and Imraldi also had no statistically significant differences in achieving a PASI score of 2 or less (Amjevita: aOR, 1.19; 95% CI, 0.94-1.51; Imraldi: aOR, 0.92; 95% CI, 0.72-1.18) and a PASI score of 4 or less (Amjevita: aOR, 1.32; 95% CI, 0.96-1.84; Imraldi: aOR, 1.00; 95% CI, 0.70-1.41) compared with those who continued Humira. In this study, Amjevita and Imraldi were as effective as Humira for both new starters and patients switching to biosimilars from Humira.

Surgical Intervention Improves Long-Term Survival in Stage IV Thymic Epithelial Tumors: Insights From a SEER Database Analysis.

This research evaluates how surgical intervention affects survival rates in individuals with stage IV thymic epithelial tumors (TET) based on data from the SEER database, offering essential information for clinical decision making. The SEER database (2004-2020) provided data on stage IV TET patients, classified into surgical and non-surgical groups. Analytical techniques, including propensity score matching (PSM) and inverse probability treatment weighting (IPTW), were employed. The primary and secondary outcomes evaluated were cancer-specific survival (CSS) and overall survival (OS), respectively. Of 634 patients (394 diagnosed with thymoma and 240 with thymic carcinoma), 335 underwent surgery, while 299 did not. In univariate analysis, those who had surgery demonstrated significantly improved CSS and OS, with 5-year survival rates of 74.6% for CSS and 62.3% for OS, compared to 41.4% and 26.0%, respectively, in the non-surgical group. Multivariate analysis identified surgery as an independent factor for better CSS and OS. After applying PSM with 194 patients in each group, surgery continued to be associated with significantly improved CSS (HR = 0.417, 95% CI: 0.297-0.587, p < 0.001) and OS (HR = 0.457, 95% CI: 0.350-0.596, p < 0.001). Inverse probability of treatment weighting (IPTW) analysis confirmed these findings, showing better CSS (HR = 0.361, 95% CI: 0.265-0.492, p < 0.001) and OS (HR = 0.423, 95% CI: 0.335-0.535, p < 0.001). Subgroup analyses underscored the survival benefit of surgery for patients with stage IV thymoma and thymic carcinoma, including those with lymph node or distant metastasis. For stage IV thymic epithelial tumors, the inclusion of surgery in multimodal treatment can improve patient survival.

Assessment of short- and long-term outcomes of aortic valve sparing operation at concomitant aortic root and arch repair.

Concomitant aortic root and arch replacement is a complex procedure. Although valve-sparing root replacement may offer advantages over valve prostheses, the decision to spare the valve may increase the risk profile of this procedure. This study examines the safety of aortic valve-sparing operation in such settings. All patients who underwent concomitant aortic root and arch replacement between 2004 and 2021 at two aortic centers were reviewed. Patients with aortic stenosis, endocarditis, or a history of previous cardiac surgery were excluded. Inverse probability treatment weighting yielded well-balanced cohorts. The primary end-points were mortality and complications during the index hospital stay, and secondary end-points were long-term survival and aortic valve reintervention rate. A total of 764 patients who underwent concomitant aortic root and arch replacement, including valve-sparing root replacement (n = 311) or composite valve graft root replacement (n = 453), were analyzed. Surgical indication was dissection in 155 (20.2%), and distal extension was total arch replacement in 50 (6.5%). Cardiopulmonary bypass and cross-clamp times were longer in valve-sparing root replacement (P = 0.006, and P < 0.001, respectively). Valve-sparing root replacement demonstrated comparable in-hospital mortality rates (2.5% vs 4.9%, P = 0.195), and showed higher long-term survival rates (P = 0.04) (12-year survival rate; 78.5% [71.7%-86.1%] vs 64.2% [57.4%-71.6%]), which was reconfirmed on multivariable Cox regression analysis (Hazard ratio: 0.505 [0.348-0.734], P < 0.001). The cumulative incidence of reintervention was similar in both groups (P = 0.62). In appropriately selected patients requiring aortic root and arch replacement, a valve-sparing operation may be performed safely without increased operative risk.

Comparison of adjuvant radiation versus observation and salvage radiation after subtotal resection of a WHO grade I skull base meningioma: a propensity score-adjusted analysis.

In patients with subtotal resection (STR) of WHO grade I skull base meningiomas, treatment strategies of adjuvant radiation versus observation with salvage radiation, if necessary, were compared using progression-free survival (PFS) and radiation failure-free survival (RFFS). Patients with newly diagnosed WHO grade I skull base meningioma who underwent radiographically confirmed STR between 1995 and 2021 were included. PFS was measured from last treatment date. RFFS was measured from surgery date to first radiation failure. Multivariable Cox regression, adjusted for propensity score (PS) and inverse probability treatment weighted (IPTW), was performed. Of 179 patients, 25 (14.0%) received adjuvant radiation. Among 154 observed patients, 90 (58.4%) experienced tumor progression and 64 (71.1%) received salvage radiation. Observation after STR had PFS at 3, 5, and 10 years of 60.6%, 47.5%, and 26.8%, respectively. Adjuvant radiation had PFS/RFFS at 3, 5, and 10 years of 84.2%, 77.2%, and 77.2%. Salvage radiation had PFS at 3, 5, and 10 years of 96.0%, 85.0%, and 80.0%. RFFS after observation with salvage radiation, if needed, at 3, 5, and 10 years was 100%, 97.7%, and 92.8%. PS and IPTW Cox regression models, controlling for residual tumor volume, demonstrated that observation with salvage radiation significantly prolonged RFFS (HR = 0.06, p = 0.013; HR 0.08, p = 0.026, respectively) compared to adjuvant radiation. Median follow-up was 77.5 months. Most patients will have tumor progression within 10 years of STR. Our data suggests that appropriately selected patients can be observed with close follow-up, reserving radiation for progression.

Administration of Evolocumab in Patients with STEMI After Emergency PCI: A Real-World Cohort Study.

Evolocumab can reduce low-density lipoprotein cholesterol (LDL-C) levels and improve cardiovascular (CV) outcomes. While its benefits are well established in broader populations, its potential impact on patients with ST-segment elevation myocardial infarction (STEMI) undergoing emergency percutaneous coronary intervention (PCI) remains underexplored, particularly in real-world settings. This study aimed to evaluate its efficacy and safety in this specific patient group on the basis of real-world clinical experience. A total of 384 patients with STEMI who underwent emergency PCI at Hebei General Hospital between 1 July 2021 and 23 September 2022 were enrolled in this retrospective, single-center study. Of these, 85 patients received evolocumab (140 mg every 2 weeks) plus standard of care (SOC), while 299 received SOC alone. Patients were monitored for CV events and lipid levels during follow-up. Propensity score matching (PSM) and inverse probability treatment weighting (IPTW) were used to balance covariates. The experimental group had a lower cumulative incidence of the primary composite endpoint over 18 months in the unadjusted analysis (hazard ratio [HR] = 0.353; 95% confidence interval [CI] 0.180-0.693; P = 0.002), as well as after adjustment for PSM (HR = 0.341; 95% CI 0.165-0.706; P = 0.004) and IPTW (HR = 0.461; 95% CI 0.241-0.881; P = 0.019). The 18-month cumulative incidence was 10 (12%) for evolocumab + SOC and 95 (32%) for SOC. LDL-C levels in the evolocumab + SOC group showed significant reductions across different cohorts, compared with the SOC group. No significant differences in adverse events were observed between the two groups. Evolocumab plus SOC significantly reduced postoperative CV events and LDL-C levels in patients with STEMI after emergency PCI.

Treatment switching between Enzalutamide and Abiraterone Acetate and time to oral opioid initiation in castration-resistant prostate cancer patients.

Treatment switching between Enzalutamide and Abiraterone Acetate and time to oral opioid initiation in castration-resistant prostate cancer patients.

Causal Effect of Count Treatment on Ordinal Outcome Using Generalized Propensity Score: Application to Number of Antenatal Care and Age Specific Childhood Vaccination

BackgroundMany of the studies in causal inference using propensity scores relied on binary treatments where it is estimated by logistic regression or machine learning algorithms. Since 2000s, attention has been given for multiple values (categorical) and continuous treatments and the propensity score associated with such treatments is called generalized propensity score (GPS). However, there is scant literature on the use of count treatments in causal inference. Besides, effective sample size, after weighting, along with other methods has not been practiced for GPS model performance measure. The study was done with the aim of using count treatments in causal inference; select appropriate GPS and outcome models for such treatment and ordinal outcome.MethodA family of count models and a generalized boosted model (GBM) were used for GPS estimation. Their performance was measured in terms of covariate balancing power, effective sample size and the average treatment effect after GPS-based weighting. Marginal structural modeling (MSM) and covariate adjustment using GPS were used to estimate treatment effect on ordinal outcome. Stabilized inverse probability treatment weighting was used for covariate balancing assessment. Monte Carlo simulation study at various sample sizes with 1000 replication and household survey data were used in the study.ResultGPS was trimmed at 1% and 99% which gave better results as compared to untrimmed results. The generalized boosted model performed well both in simulation and actual data producing a larger effective sample size and smaller metrics when estimating average treatment effect on the outcome. The MSM was found better than GPS as a covariate in the outcome model.ConclusionIt is important to trim GPS when it approaches zero or one without loss of more information due to trimming. Effective sample size after weighting should be used along with other methods such as correlation and absolute standardized mean differences for GPS model selection. GBM should be used for GPS estimation for count treatments. MSM is important for the outcome model when weighting GPS method is used. Finally, the number of antenatal care services had an increasing effect on the probability of age-specific childhood vaccination.

Effectiveness of an integrated cerebral protection protocol in type A aortic dissection surgery: an inverse probability treatment weighting analysis

BackgroundCerebral protection strategies in type A aortic dissection (TAAD) surgery are critical yet inconclusive. We propose an integrated cerebral protection protocol. This study aimed to evaluate the effectiveness of this protocol.MethodsFrom January 2020 to December 2022, 85 patients were treated with an integrated protocol incorporating bilateral antegrade cerebral perfusion (ACP) and moderate hypothermia, with measures to prevent the shedding of thrombus or endothelial debris (BACP group), while traditional protocols were applied to 273 additional patients (UACP group). Inverse probability treatment weighting (IPTW) was performed to balance baseline characteristics. Three logistic regression models were used to evaluate the relationship between the two cerebral protection strategies and neurologic complications. Stepwise logistic regression was further employed to identify risk factors for cerebral complications.ResultsBaseline characteristics were balanced after IPTW adjustment. The BACP group had a significantly shorter operative time (364.79 vs. 397.61 min, P = 0.022), significantly fewer neurologic complications (5.6% vs. 15.9%, P = 0.032), and transient neurologic injury (3.0% vs. 12.5%, P = 0.035). Binary multivariable logistic regression analysis showed that the cerebral complication risk was 3.14 times greater with the traditional protocol compared to the integrated protocol (odds ratio[OR]:3.14, 95%confidence interval[CI]:1.19–8.27, P = 0.020). Stepwise logistic regression confirmed that cerebral complications were dramatically increased with unilateral ACP (OR:2.99, 95%CI:1.14–7.82, P = 0.025), while bilateral ACP had a significant impact on decreasing cerebral complications.ConclusionsOur integrated protocol effectively minimizes postoperative cerebral complications. Moderate hypothermia combined with BACP and measures to prevent brain debris could be adopted as an effective strategy for cerebral protection in TAAD surgery.

Real-world disease burden, mortality, and healthcare resource utilization associated with bronchiectasis.

To assess real-world survival and healthcare resource utilization (HCRU) in US patients with non-cystic fibrosis bronchiectasis (NCFBE). This retrospective analysis, using data from the STATinMED RWD Insights database from Jan 2015-Oct 2022, included adults with NCFBE (from Jan 2015-Oct 2021) and non-NCFBE comparators (from Jan 2015-Aug 2020); baseline characteristics were balanced by inverse probability treatment weighting. Outcomes included survival through end of study. HCRU was assessed over 12months. 117,718 patients with NCFBE and 306,678 comparators were included. Patients with NCFBE had a 77% higher risk of death than comparators (hazard ratio [HR] 1.77 [95% CI 1.74-1.80]). Risk of death was higher among patients aged ≥65years (vs 18-34years; HR 11.03 [95% CI 10.36-11.74]), among Black patients (vs White; HR 1.53 [95% CI 1.50-1.55]), and among patients with comorbid COPD (HR 1.42 [95% CI 1.40-1.44]). Patients with NCFBE incurred higher all-cause and respiratory-related HCRU than comparators for outpatient office, outpatient hospital, emergency department (ED), inpatient and respiratory-related pulmonologist visits (all p < .0001); HCRU increased with exacerbations. Patients with NCFBE have high mortality burden and incur high HCRU, both of which are further increased with exacerbations. Prevention and delay of exacerbations are key areas for improvement of disease management.

Estrogen Treatment Lowers the Risk of Complications in Menopausal Women with Mild Burn Injury.

Background and Objectives: Postmenopausal women are often treated with exogenous female hormones to alleviate physical symptoms and support mental health. We posit that women treated with estrogen fare better following burn injury. Materials and Methods: De-identified patient data were obtained from TriNetX, a global healthcare research network. Adult postmenopausal women were enrolled if they were diagnosed with burn injury within 10 years after menopause onset. Patients with pre-existing abnormal uterine bleeding, gynecologic cancer, and chronic liver or heart disease were excluded. The population was grouped into those who received and those who did not receive estrogen treatment (ET) for evaluation of subsequent complications. Cohort balancing was performed using the exact match approach of Inverse Probability Treatment Weighting (IPTW). The average treatment effects (ATEs) and confidence intervals were computed for these balanced cohorts. Results: Postmenopausal women with ET had a lower risk of endometrial hyperplasia and malignancy 3 months (ATE = -0.005, -0.006) and 3 years (-0.007, -0.008) after mild burn injury (less than 20% of total body surface area) (p < 0.05), regardless of age. At the 3-month timepoint, postmenopausal women aged 45-65 with ET exhibited preventive effects against acute kidney injury (-0.0332), cerebral infarction (-0.0279), breast cancer (-0.0278) and severe sepsis (-0.011) after mild burn injury (p < 0.05) compared to women who did not receive ET. After 3 years, 45-65-year-old women with ET exhibited decreased rates of breast cancer (-0.0479) and endometrial hyperplasia (-0.0116) (p < 0.05) compared to those without ET. Conclusions: Estrogen treatment decreases the risk probabilities of breast cancer and other complications in postmenopausal women from 3 months to 3 years after mild burn injury.

Pulse-by-pulse treatment planning and its application to generic observations of ultra-high dose rate (FLASH) radiotherapy with photons and protons

Objective.The exact temporal characteristics of beam delivery affect the efficacy and outcome of ultra-high dose rate (UHDR or 'FLASH') radiotherapy, mainly due to the influence of the beam pulse structure on mean dose rate. Single beams may also be delivered in separate treatment sessions to elevate mean dose rate. This paper therefore describes a model for pulse-by-pulse treatment planning and demonstrates its application by making some generic observations of the characteristics of FLASH radiotherapy with photons and protons.Approach.A beam delivery model was implemented into the AutoBeam (v6.3) inverse treatment planning system, so that the individual pulses of the delivery system could be explicitly described during optimisation. The delivery model was used to calculate distributions of time-averaged and dose-averaged mean dose rate and the dose modifying factor for FLASH was then determined and applied to dose calculated by a discrete ordinates Boltzmann solver. The method was applied to intensity-modulated radiation therapy with photons as well as to passive scattering and pencil beam scanning with protons for the case of a simple phantom geometry with a prescribed dose of 36 Gy in 3 fractions.Main results.Dose and dose rate are highest in the target region, so FLASH sparing is most pronounced around the planning target volume (PTV). When using a treatment session per beam, OAR sparing is possible more peripherally. The sparing with photons is higher than with protons because the dose to OAR is higher with photons.Significance.The framework provides an efficient method to determine the optimal technique for delivering clinical dose distributions using FLASH. The most sparing occurs close to the PTV for hypofractionated treatments.

Efficacy and safety of switching from entecavir to tenofovir alafenamide in chronic hepatitis B patients with low-level viremia: a real-world 48-week extension study.

Chronic hepatitis B (CHB) patients receiving entecavir (ETV) treatment might develop low-level viremia (LLV), which is proven to be associated with worse clinical outcomes, such as risk of drug-related mutations, progression to cirrhosis, and even hepatocellular carcinoma. This real-world prospective study evaluated the efficacy and safety of switching from ETV to tenofovir alafenamide fumarate (TAF) in CHB patients with LLV. From August 2020 to August 2023, 351 ETV-experienced CHB patients with LLV were enrolled from eight hospitals. Patients either continued ETV or switched to TAF. The primary efficacy endpoint was the complete virological response (CVR) at week 48; the safety endpoint was the first occurrence of any clinical adverse event during the treatment; and the renal safety and change in blood lipids were also assessed. Inverse probability treatment weighting (IPTW) generated 350.9 cases in the ETV group and 351.4 cases in the TAF group. After the 48-week treatment, the CVR and ALT normalization rates in the TAF group were 75.3% and 67.8%, which were significantly higher than 11.4% and 17.1% in the ETV group (P < 0.001). The two strategies showed comparable impact on renal function and lipid profiles, regarding low-density lipoprotein (LDL) cholesterol and the total cholesterol to high-density lipoprotein (TC/HDL) ratio. Therefore, for ETV-treated patients with LLV, switching to TAF is superior compared with continuing ETV treatment in terms of virological and biochemical response, with non-inferior renal safety and lipid profiles.CLINICAL TRIALSThis study is registered with the Chinese Clinial Trial Registry as ChiCTR2400089257.

Efficacy of laparoscopic parenchyma-sparing hepatectomy using augmented reality navigation combined with fluorescence imaging for colorectal liver metastases: a retrospective cohort study using inverse probability treatment weighting analysis.

Laparoscopic parenchyma-sparing hepatectomy (PSH) is an effective treatment for colorectal liver metastases (CRLMs), but ensuring the safety and radicality of the procedure, particularly for deep-seated tumors, remains challenging. Surgical navigation technologies such as augmented reality navigation (ARN) and indocyanine green fluorescence imaging (ICG-FI) are increasingly utilized to guide surgery, yet their efficacy for CRLMs is unclear. This study aims to evaluate the short-term and long-term outcomes of ARN combined with ICG-FI-guided (ARN-FI) laparoscopic PSH for CRLMs. Between January 2020 and December 2022, 89 consecutive patients who underwent laparoscopic PSH for CRLMs were included in the study. Patients were divided into an ARN-FI group ( n =38) and a non-ARN-FI group ( n =51) based on the use of ARN-FI. Inverse probability treatment weighting (IPTW) was used to balance baseline characteristics and minimize potential selection bias. Short-term and long-term outcomes were compared between the two groups. Cox regression analysis was conducted to identify risk factors associated with recurrence-free survival (RFS) and hepatic RFS. After IPTW, there were 87 patients in the ARN-FI group and 89 patients in the non-ARN-FI group. Shorter parenchymal transection time, postoperative hospital stays, and wider margins were observed in the ARN-FI group. There was no significant difference in RFS or hepatic RFS between the groups. Mutant KRAS status was an independent risk factor for both RFS and hepatic RFS, while tumor diameter≥5 cm and deep-seated location were risk factors for hepatic RFS. In the subgroup analysis of deep-seated tumors, the ARN-FI group also showed less intraoperative blood loss, a lower rate of strategy change, shorter postoperative recovery times, a higher R0 resection rate, and improved RFS and hepatic RFS. In laparoscopic PSH for CRLMs, ARN-FI may improve surgical efficiency and accuracy. Especially for deep-seated tumors, it has the potential to reduce blood loss and attain higher R0 resection rates.

Risk of poor glycemic control in tamsulosin versus finasteride users with type 2 diabetes mellitus.

Risk of poor glycemic control in tamsulosin versus finasteride users with type 2 diabetes mellitus.

Oncologic Outcomes of Laparoscopic Radical Hysterectomy Incorporating Modified Tumor-Free Techniques.

It remains unclear whether modifying laparoscopic radical hysterectomy to adopt tumor-free principles can improve oncologic outcomes in patients with early-stage cervical cancer. We performed a single-center retrospective cohort study of 276 patients with early-stage cervical cancer who were treated between January 2017 and January 2023, including 151 patients who underwent laparoscopic radical hysterectomy that incorporated modified tumor-free techniques (MTF group) and 125 patients who underwent conventional laparoscopic radical hysterectomy with a uterine manipulator and unprotected intracorporeal colpotomy (non-MTF group). Oncologic outcomes and perioperative results were analyzed using inverse probability treatment weighting (IPTW). Patients in the MTF group had shorter length of hospital stay than those in the non-MTF group. However, there were no significant differences in operative time, decrease in hemoglobin, or complications. After a median follow-up of 36.0 months (range 15.3-62.0 months) for the MTF group and 66.8 months (range 3.0-82.5 months) for the non-MTF group, recurrence was observed in two (1.3%) and 16 (12.8%) of the patients, respectively. The 2-year disease-free survival (DFS) rates in the MTF group and non-MTF group were 99.3% and 91.9%, respectively. In the primary analysis limited to 2-year survival, the adjusted multivariate analysis showed that use of modified tumor-free techniques was an independent predictor of longer DFS (hazard ratio 0.10 95% CI, 0.01-0.77, P =.027). After IPTW, patients in the MTF group had a more favorable DFS than those in the non-MTF group (log-rank P =.031). Laparoscopic radical hysterectomy that incorporates modified tumor-free techniques is a feasible treatment for patients with early-stage cervical cancer. Oncologic outcomes of individuals who underwent this procedure were more favorable than those of conventional laparoscopic radical hysterectomy.

Contrast-enhanced intraoperative ultrasound improved hepatic recurrence-free survival in initially unresectable colorectal cancer liver metastases

Contrast-enhanced intraoperative ultrasound improved hepatic recurrence-free survival in initially unresectable colorectal cancer liver metastases

Integrating lymph node ratio into personalized radiotherapy for oral cavity squamous cell carcinoma.

The use of postoperative radiotherapy (PORT) in patients with oral squamous cell carcinoma (OCSCC) lacks clear boundaries due to the non-negligible toxicity accompanying its remarkable cancer-killing effect. This study aims at validating the ability of deep learning models to develop individualized PORT recommendations for patients with OCSCC and quantifying the impact of patient characteristics on treatment selection. Participants were categorized into two groups based on alignment between model-recommended and actual treatment regimens, with their overall survival compared. Inverse probability treatment weighting was used to reduce bias, and a mixed-effects multivariate linear regression illustrated how baseline characteristics influenced PORT selection. 4990 patients with OCSCC met the inclusion criteria. Deep Survival regression with Mixture Effects (DSME) demonstrated the best performance among all the models and National Comprehensive Cancer Network guidelines. The efficacy of PORT is enhanced as the lymph node ratio (LNR) increases. Similar enhancements in efficacy are observed in patients with advanced age, large tumors, multiple positive lymph nodes, tongue involvement, and stage IVA. Early-stage (stage 0-II) OCSCC may safely omit PORT. This is the first study to incorporate LNR as a tumor character to make personalized recommendations for patients. DSME can effectively identify potential beneficiaries of PORT and provide quantifiable survival benefits.

Derivation of a multivariate longitudinal causal effects model

This paper presents a causal inference estimation method for longitudinal observational studies with multiple outcomes. The method uses marginal structural models with inverse probability treatment weights (MSM-IPTWs). In developing the proposed method, we re-define the weights as a product of inverse weights at each time point, accounting for time-varying confounders and treatment exposures and possible correlation between and within (serial) the multiple outcomes. The proposed method is evaluated by simulation studies and with an application to estimate the effect of HIV positivity awareness on condom use and multiple sexual partners using the Malawi Longitudinal Study of Families and Health (MLSFH) data. The simulation study shows that the joint MSM-IPTW performs well with coverage within the expected 95% level for a large sample size (n = 1000) and moderate to strong between and within outcome correlation strength ( ρ j = 0.3 , 0.75, ρ k = 0.4 , 0.8) when the effects are similar. The joint MSM-IPTW performed relatively the same as the adjusted standard joint model when the treatment effect estimate was the same for the outcomes. In the application, HIV positivity awareness increased the usage of condoms and did not affect the number of sexual partners. We recommend using the proposed MSM-IPTWs to correctly control for time-varying treatment and confounders when estimating causal effects for longitudinal observational studies with multiple outcomes.

Attitude towards a moderate aortic valve dysfunction during rheumatic mitral valve surgery: a retrospective cohort study.

There are insufficient data regarding how to deal with moderate aortic valve (AV) dysfunction during rheumatic mitral valve (MV) surgery. In this study, the clinical outcomes of patients who underwent rheumatic MV surgery with or without concurrent AV procedures were compared. A total of 343 patients who underwent rheumatic MV surgery with moderate AV dysfunction were enrolled between January 2015 and August 2022, and a median 40-month follow-up was conducted. The more-than-mild AV dysfunction during follow-up was the primary endpoint event, while all-cause mortality and cardiac reoperation both before discharge and during follow-up encompassed the secondary endpoint events. Patients were allocated into two groups, including the no treatment (NT) (n=121) and aortic valvuloplasty (AVP) or aortic valve replacement (AVR) groups (n=222). Most of patients (110/121, 90.9%) in the NT group were combined with predominant aortic regurgitation. In the NT and AVP or AVR groups, 27.9% and 8.0% of patients reached the primary endpoint, and 5.0% and 7.3% of patients experienced the secondary endpoint events, respectively. This study confirmed a significantly higher proportion of patients in the NT group who reached the primary endpoint (relative risk, 2.98; 95% confidence interval: 1.61-5.62; P<0.001), after inverse probability treatment weighting. Concomitant AV surgery significantly improved AV condition during follow-up for patients with moderate AV dysfunction during rheumatic valve surgery. However, it was safe and reasonable to delay surgical treatment of the AV and regular follow-ups for patients with predominant moderate aortic regurgitation.

Short (2-Hour) Non-Oxygenated End-Ischemic Hypothermic Perfusion Versus Cold Storage in the Setting of Renal Transplantation.

Kidney transplantation (KT) is the most effective treatment for end-stage renal disease. End-ischemic hypothermic machine perfusion (EI-HMP) has emerged as a promising method for preserving grafts before transplantation. This study aimed to compare graft function recovery in KT recipients of deceased brain-death (DBD) grafts preserved with EI-HMP versus static cold storage (SCS). The primary outcome was the rate of delayed graft function (DGF). Secondary outcomes included urine output, intensive care unit (ICU) stay, hospital stay duration, and survival rates. A retrospective, single-center observational study was conducted at Sapienza University of Rome, analyzing 313 KT patients between January 2014 and September 2021. Patients were stratified into two groups based on graft preservation methods (EI-HMP, n = 95; SCS, n = 218). A stabilized inverse probability treatment weighting (IPTW) method was employed to adjust for potential confounders. There were no significant differences in DGF rates between the two groups (17.9% vs. 15.6% in SCS and EI-HMP cases, respectively; p = 0.75). EI-HMP group demonstrated a higher urine output on day 2 (p = 0.046), a shorter ICU stay (p < 0.0001), and a trend toward a shorter overall hospital stay (p = 0.07). No statistically significant differences were found between EI-HMP and SCS cases in 1- and 3-year overall survival rates (3.2% and 6.7% vs. 5.6% and 6.6%, respectively; log-rank p = 0.53) or in death-censored graft loss rates (5.4% and 8.9% vs. 5.7% and 7.3%, respectively; log-rank p = 0.88). In a sub-analysis of expanded criteria donors (ECD), EI-HMP demonstrated a protective effect by reducing the risk of DGF (OR = 0.31, 95% CI = 0.09-0.95; p = 0.047). EI-HMP was associated with certain short-term benefits, including increased urine output and reduced ICU stays, but showed no significant impact on long-term survival outcomes. A reduction in DGF rates was observed only in the ECD subgroup. Randomized controlled trials are necessary to further investigate the long-term clinical benefits of EI-HMP.