Two-year Survival Research Articles

Mid-term follow-up results of neoadjuvant sintilimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma.

The study was conducted in order to investigate whether neoadjuvant immunotherapy combined with chemotherapy can bring survival benefits to patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC) in the real world. We retrospectively analysed patients with locally advanced resectable ESCC who underwent surgery at the Jining First People's Hospital from April 2020 to April 2022. Based on their medical history, the enrolled patients were divided into a neoadjuvant immunochemotherapy plus surgery group (nICT group) and a surgery-only group (S group). Primary endpoints were the two-year overall survival (OS) and disease-free survival (DFS) rates. Secondary endpoints were the safety and efficacy of neoadjuvant immunochemotherapy for patients with locally advanced esophageal cancer, and compared the surgery and postoperative outcomes between the two groups. A total of 47 patients in the nICT group and 73 patients in the S group were included for further analysis, the stage of the nICT group was more advanced than that of the S group. In the group nICT, 8 patients (17%) achieved the complete pathological response (pCR), 29 patients (61.7%) achieved major pathological response (MPR), including 6 patients (12.8%) with a primary tumor achieving pCR but had residual tumor cells in the lymph nodes (pT0N+), and the treatment-related AES was manageable. The surgery and postoperative outcomes were comparable in both groups. The two-year OS and DFS rates for the nICT group were 91.5% and 85.5% respectively, while those for the S group were 71.2% and 68.5%, and Kaplan-Meier survival analysis and log-rank test revealed significant differences in DFS and OS between the two groups. Patients who achieved MPR in the nICT group showed better DFS and OS, while the Three-cycle subgroup did not exhibit any survival benefit compared to the Two-cycle subgroup. Neoadjuvant sintilimab combined with chemotherapy has promising efficacy and safety in the treatment of locally advanced resectable ESCC. The treatment modality has the potential to become a standard therapy for locally advanced resectable ESCC.

Cutibacterium acnes periprosthetic joint infections.

Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee. Patients with C. acnes PJI between January 2005 and December 2018 were retrospectively reviewed utilizing the institutional total joint registry. Patients with monomicrobial PJI and two or more positive cultures were considered to have true C. acnes PJI. Patients with polymicrobial infection or with only one positive culture were excluded. This resulted in 35 PJIs (21 hips and 14 knees); the patients' mean age was 63 years (35 to 84) and 15 (43%) were female. Mean follow-up was five years (1 to 14). The median time to positive culture was five days (IQR 5 to 6) and median synovial fluid cell count was 22,583 cells (IQR 15,200 to 53,231). The median ESR was 25 mm/hr (IQR 7 to 37), and CRP was 15 mg/l (IQR 3 to 29). Of the 35 PJIs, 18 (51%) were treated with chronic antibiotic suppression without surgical intervention, and the remainder were treated with two-stage exchange arthroplasty. The two-year survival free of any revision was 94%. Four patients failed treatment due to symptomatic infection, with three treated with two-stage exchange and one treated with irrigation and debridement with modular component exchange for a survival rate of 89% and 83% at two and five years, respectively. Laboratory evidence of C. acnes PJI in this cohort was typical compared to more conventional organisms. Cultures grew more quickly than previously thought in patients with C. acnes PJI. Treatment with two-stage exchange or chronic antibiotic suppression alone both had few treatment failures at mid-term follow-up.

Трансплантація серця в Україні: досвід одного центру

The aim – to show and analyze our own experience of performing orthotopic heart transplantation in patients with end-stage chronic heart failure.Materials and methods. The work retrospectively analyzed the results of 106 cases of orthotopic heart transplantation in adults and children, which were performed by the heart transplantation team of the Heart Institute of the Ministry of Health of Ukraine during 2019–2024.Results. Standard donor hearts were received by 67 (63.3 %) recipients. Marginal donor hearts were used in 39 (36.7 %) cases. In 97 (91.5 %) cases, patients underwent isolated orthotopic heart transplantation. In other cases, coronary artery bypass grafting was performed in 4 (3.75 %) cases, correction of valvular pathology of the donor heart – in 4 (3.75 %) cases, and correction for congenital heart disease – in 1 case. The median duration of ischemia time of the donor heart was 80 (70; 95) minutes. Among the postoperative complications, the most common was a primary graft dysfunction – in 11 (10.4 %) cases. There was no statistical difference in the frequency of postoperative complications between patients with marginal or standard donor hearts. One-year and two-year survival according to Kaplan–Meier was 88.4 ± 4.5 % (95 % CI 81.9–95.5 %) and 86.7 ± 5.7 % (95 % CI 75.9–94.5 %).Conclusions. Our first experience with heart transplantations showed encouraging immediate and medium-term results. Due to the use of marginal donor hearts, we were able to increase the donor organ pool by 40 %. Follow-up is ongoing.

Comparison of the effectiveness of supportive chemotherapy for patients with acute myeloid leukemia

Introduction. Achieving complete remission and prolonging event-free survival is the primary task of chemotherapeutic treatment for patients with acute myeloid leukemia (AML). Supportive therapy is a possible way to maintain complete remission.Aim: to compare two variants of supportive treatment (5+5 and 6-MP + Mtx) in patients with AML in the first complete remission after completion of the induction and consolidation programs.Materials and methods. The single-center randomized study included 34 AML patients treated from 2017 to 2021. The median age was 36 (18–56) years, the ratio of men to women was 18:16. After completing the induction and consolidation program, randomization was performed for different branches of supportive chemotherapy: 5+5 (cytarabine 50 mg/m2 2 times/day, mercaptopurine 60 mg/m2 days 1–5, a total of 6 courses) — first group (18 patients), and 6-MR + Mtx (6-mercaptopurine 50 mg/m2 daily, methotrexate 15 mg/m2 once/week) — second (16 patients). Courses of maintenance therapy were conducted until the total completion of treatment, the implementation of allogenic hematopoietic stem cell transplantation (allo-HSCT), the development of relapse, or death of the patient.Results. The two-year overall survival in the 5+5 group was 93 %, in 6-MP + Mtx group 68 % (p = 0.0814). Mortality in both groups was associated with complications in the post-transplant period. The actual OS and the hypothetical one — without performing allo-HSCT, did not differ. Thus, the fact of performing allo-HSCT does not affect the effectiveness of maintenance therapy courses. The two-year disease-free survival rate (DFS) was 66 % in the 5+5 group and 63 % in the 6-MP + Mtx group (p = 0.42). From the time of randomization, 8 patients (24 %) have relapsed and 1 patient died from complications after allo-HSCT.Conclusion. During treatment under the maintenance therapy programs 5+5 and 6-MP+Mtx, similar OS and RFS were achieved. During 5+5 program, hospitalization in a day hospital is required. The 6-MP+Mtx program has similar effectiveness, however, the entire period of supportive treatment can be carried out on an outpatient basis but lasts 24 months compared to 6 months when using the 5+5 program. The choice of maintenance therapy according to the 5+5 program is optimal from the point of view of the quality of life of patients.

Left Ventricular Ultrasound Diastolic Parameters in Postmenopausal Breast Cancer Patients Treated with Adjuvant Anthracycline and Trastuzumab

Background: Breast cancer remains the leading cause of cancer-related deaths among women of all ages. As age increases, so does the risk of both cancer and cardiovascular diseases, heightening the likelihood of short-term and long-term cardiovascular side effects. Therefore, strategies for early diagnosis and prevention of cardiotoxicity are crucial. he optimal use of conventional echocardiographic parameters is important, especially given the limited access to advanced echocardiography in developing countries. Aims: To evaluate changes in left ventricular (LV) ultrasound parameters, including diastolic parameters, in postmenopausal women with breast cancer (BC), as a high-risk group receiving anthracycline-trastuzumab-containing regimens. Study Design: A prospective 24-month single-center study. Place and Duration of Study: From December 2019 to March 2024 at the ultrasound laboratory of Tbilisi State University Medical Center, Tbilisi, Georgia Methodology: Seventy-four postmenopausal patients with primary BC receiving anthracycline or anthracycline-trastuzumab were assessed for LV systolic and diastolic parameters before the anticancer therapy and at six subsequent visits. Cardio-protection was administered to high-risk patients preventively and to others when cardiotoxicity developed. Multiple regression was used to estimate relationships between various independent and dependent variables. Cardiotoxicity was assessed using survival analysis tools (Kaplan-Meier curves and Cox proportional model). Results: The two-year CTRCD survival rate was 63.5%. During the 2-year follow-up, the mean E/e' increased across the entire cohort, but remained within the normal range. E/e' >15 was noted only in CTRCD patients at 6th month mark (4.1%, n=3, P=.056) within the high-risk group, peaking at 9th month (10.8%, n=8, P< .00). Multiple regression indicated a significant association of IVRT baseline value with late cardiotoxicity (adj. beta-coefficient= 0.32; t = 2.73, P=.008) and DT baseline value with early cardiotoxicity (adj. beta-coefficient = -0.25; t = -3.31, P=0.002). GLS demonstrated predictive value from the first month in 13.5% of the cohort and in 34.5% of patients with CTRCD (P< .00). Conclusion: Our 2-year longitudinal prospective study of anthracycline–trastuzumab-containing regimens in postmenopausal women with early BC revealed that: 1) Predictive association of E/e' with cardiotoxicity was not detected. 2) A reliable association with late cardiotoxicity (T7) from the diastolic parameters was revealed only by IVRT baseline value 3) A reliable association with early cardiotoxicity (T4) from diastolic parameters was revealed only by DT baseline. 4)GLS is superior to E/e' in its prognostic value and diagnostic ability of cardiotoxicity .

A comparative study on outcomes of ABO-incompatible kidney transplants between robot-assisted vs. open surgery-propensity score-matched analysis: a retrospective cohort study

BackgroundRobot-assisted kidney transplantation (RAKT) is increasingly being adopted worldwide. Despite this growing interest, there remains a notable gap in the literature, especially concerning its effectiveness in immunologically high-risk patients compared to conventional open kidney transplantation (OKT). This study investigates the viability and success of RAKT in comparison with OKT, particularly for recipients with ABO incompatibility (ABOi).MethodsThis retrospective, single-center study included 239 living-donor transplants between October 2020 and February 2023, with 210 patients undergoing ABOi-OKT and 29 undergoing ABOi-RAKT. A composite of biopsy-proven acute rejection (BPAR), graft failure, and the development of de novo donor-specific antibodies was analyzed through univariate and multivariate models. Propensity score matching (PSM) was utilized to ensure a balanced comparison between the two groups. Following PSM, a total of 131 cases in the OKT group and 26 cases in the RAKT group were analyzed.ResultsAfter PSM, the mean recipient age was 48.56 years for OKT and 47.96 years for RAKT. Both groups had comparable one-year (RAKT: 92.4%, OKT: 93.1%) and two-year BPAR-free survival rates (RAKT: 92.4%, OKT: 91.9%). Mean estimated glomerular filtration rate values were similar at 12 months post-transplant (RAKT: 62.15 ml/min/1.73 m², OKT: 64.53 ml/min/1.73 m²). Operative times were significantly longer for RAKT (291.42 vs. 150.81 min, p < 0.001), while cold ischemic time was also longer for RAKT (119.77 vs. 47.22 min, p < 0.001). Hospital stays were shorter for RAKT (median 6 vs. 8 days, p < 0.001). There was no significant difference in the composite outcome of BPAR, graft failure, and de novo donor-specific antibodies between the two groups (HR 0.858, 95% CI: 0.180–4.096, p = 0.848).ConclusionsRAKT is a safe and effective alternative to OKT in ABOi patients, demonstrating similar perioperative outcomes, graft survival rates, and renal function. The application of ropensity score matching analysis strengthens the reliability of these findings, confirming RAKT’s viability for high-risk kidney transplant recipients.Trial registrationThe clinical trial associated with this study was registered on 2024-02-24 with the Clinical Trial Number NCT06287008||https://www.clinicaltrials.gov/)

OGC SO04 - Impact of COVID-19 on Decision-making and Survival in Esophago-Gastric Cancer Treatment: Insights from a Multidisciplinary Approach

Abstract Background The COVID-19 pandemic necessitated rapid adaptation in healthcare delivery, affecting cancer care pathways. This study assesses the impact of these changes on multidisciplinary team (MDT) decision-making and survival outcomes in esophago-gastric cancer patients across pre-pandemic, peak pandemic, and post-pandemic periods. Method A retrospective cohort study involving patients referred to a UK tertiary EG cancer center during distinct six-month intervals mirroring the pandemic's evolution. Analysis focused on MDT recommendations, treatment pathways, and two-year survival rates, comparing deviations from standard care across periods. Results The study revealed a significant reduction in patient referrals and expedited treatment decisions during the pandemic peak, with a shift towards palliative care in post-pandemic cases. Although no statistically significant difference in two-year survival rates was observed, the post-pandemic period showed an increase in tumor aggressiveness and positive resection margins, suggesting potential long-term impacts of delayed diagnosis and treatment. Conclusion COVID-19 has significantly influenced MDT decision-making and patient pathways in esophago-gastric cancer care, underlining the necessity of resilient healthcare systems. Despite maintaining survival rates, the observed increase in tumor aggressiveness post-pandemic highlights the critical need for uninterrupted cancer diagnosis and treatment services during global health emergencies.

Local Endoscopic Treatment of Low-Grade Urothelial Tumors in the Upper Urinary Tract-Oncological Outcome of a Consecutive Single-Center Series of 118 Patients.

Upper urinary tract urothelial tumors are mostly treated with the use of endoscopic laser ablation. The treatment is recommended when the tumor is low grade and non-invasive. The aim of the present study was to investigate the oncological outcome of patients treated endoscopically for low-grade (LG) upper tract urothelial carcinoma (UTUC). One hundred and eighteen consecutive patients with pTa LG UTUC initially treated with laser ablation from 2012-2022 at a single university hospital were included. Patient and tumor characteristics, treatment, and oncological outcomes were retrospectively registered from electronic medical journals. Survival analysis was performed using Kaplan-Meier and Nelson-Aalen plots. The median number of local recurrences was 2 with a median time to first recurrence of 5 months (IQR: 2-46). The 2-year share of patients having no recurrence was 28.8%. The risk of recurrence was highest within the first 3 years following initial treatment. Two-year survival function with no progression and preserved renal unit was 67.9%. The two-year overall survival (OS) and disease-specific survival (DSS) were 84.2% and 97.1%. The 5-year OS and DSS were 59.1% and 94.1%. The median follow-up time for OS was 36 months (IQR: 20.3-58.8). In the patient series, we found that the risk of recurrence following laser ablation of LG UTUC was high; however, it was associated with a low risk of progression and high OS and DSS. Therefore, we conclude that treatment with laser ablation in patients with LG UTUC is safe, although frequent follow-up is needed to detect recurrence.

Arsenic trioxide versus Realgar-Indigo naturalis formula in non-high-risk acute promyelocytic leukemia: a multicenter, randomized trial.

Realgar-Indigo Naturalis Formula (RIF) is an oral form of arsenic that is effective against acute promyelocytic leukemia (APL). This multicenter, randomized, controlled trial compared the efficacy of all-trans retinoic acid (ATRA) plus RIF with ATRA plus arsenic trioxide (ATO) in a simplified regimen for non-high-risk APL. Following induction therapy with ATRA and ATO, participants were randomly assigned to receive either ATRA plus ATO or ATRA plus RIF both in a 2-week on 2-week off schedule for consolidation therapy. Once achieving molecular complete remission, the regimen was administered for a total of 6 cycles. All of 108 eligible patients achieved hematological complete remission after induction therapy. The median follow-up time was 29 months. The primary endpoint of two-year disease-free survival was 97% in the ATRA-RIF arm and 98% in the ATRA-ATO arm, respectively. (The ATRA-RIF arm was found to be non-inferior to the ATRA-ATO arm, (P < .01), with a percentage difference of -1% (95%CI, -4.8 to 6.9). No deaths have been observed. Most adverse events were moderate. This study confirms the noninferiority of RIF to ATO for non-high-risk APL, while also offering a more favorable regimen schedule for post-remission therapy. (ClinicalTrials gov. Identifier: as NCT02899169).

Evolution of treatment strategies for solid tumors with RET rearrangement in China and real-world treatment status of Non-small Cell Lung Cancer (NSCLC)

ObjectiveThe present study endeavors to furnish an exhaustive review of the research advancements on solid tumors harboring RET rearrangement within the Chinese context, particularly emphasizing the examination of real-world therapeutic strategies and clinical outcomes observed in individuals diagnosed with advanced non-small cell lung cancer (NSCLC). The review delves into a critical assessment of the therapeutic efficacy of targeted RET inhibitors, while also scrutinizing the diverse array of treatment modalities employed in the Chinese patient population.MethodsThe study conducted a comprehensive review of the advancements made by Chinese scholars in the realm of RET driver genes. It delved into the analysis of the incidence of RET rearrangements in solid tumors, alongside an examination of the varied treatment paradigms and their current status within China. Utilizing the RECIST 1.1 criteria, the study evaluated the therapeutic efficacy achieved in RET-positive NSCLC patients undergoing diverse treatment modalities. Furthermore, treatment-related adverse events (TRAEs) were meticulously graded following the Common Terminology Criteria for Adverse Events (CTCAE).ResultsA retrospective, multi-center, real-world analysis was conducted, encompassing 64 patients diagnosed with pathologically confirmed RET rearrangement advanced non-small cell lung cancer (NSCLC) between December 2015 and November 2023. Notably, KIF5B-RET emerged as the most prevalent RET fusion partner, accounting for 59.4% of cases. Therapeutic interventions among these patients included specific targeted inhibitors such as Pralsetinib (48.4%), chemotherapy (34.3%), multi-target inhibitors (15.6%), and one case (1.6%) involving immunotherapy combined with anti-angiogenic therapy. In terms of progression-free survival (PFS), Pralsetinib monotherapy demonstrated a median PFS of 16.03 months, outperforming chemotherapy (2.87 months; p < 0.0001), chemotherapy combined with anti-angiogenic therapy (6.90 months; p = 0.048), and multi-target inhibitors (2.50 months; p < 0.0001). Furthermore, the one-year and two-year overall survival (OS) rates for Pralsetinib monotherapy were 64.3% and 46.4%, respectively. Regarding safety, 71.0% of patients receiving Pralsetinib experienced at least one adverse event, with 45.2% classified as grade 3–4 in severity. Notably, no fatalities were attributed to adverse events. Common adverse events included hemoglobin reduction (35.5%) and neutropenia (32.3%), indicative of an overall favorable safety profile for Pralsetinib in this patient population.ConclusionThis study encapsulates the research endeavors and treatment advancements of RET rearrangement solid tumors within the Chinese healthcare landscape, specifically highlighting the diverse real-world therapeutic approaches and their effectiveness in managing advanced RET rearrangement NSCLC among Chinese patients. Notably, targeted RET inhibitors like Pralsetinib have emerged as potent therapeutic agents, exhibiting remarkable efficacy and a manageable safety profile in this patient cohort. These findings underscore the potential of Pralsetinib and similar targeted therapies as novel treatment options for individuals with RET fusion-positive NSCLC.

Outcomes and Perioperative Complications of Surgical Resection on Canine Carotid Paragangliomas (21 Cases): A Veterinary Society of Surgical Oncology Study.

Carotid body paragangliomas represent an uncommon neoplasm in dogs. The objective of this study was to report outcomes and complications associated with surgical excision of carotid body paragangliomas in 21 dogs. Cases were recruited retrospectively via medical record review from 9 veterinary speciality centres. The perioperative complication rate was 52% (11/21). Complications encountered in this cohort related to removal of carotid body tumour included airway obstruction, aspiration pneumonia, megaesophagus, unilateral laryngeal paralysis, coughing and Horner's syndrome. The overall perioperative mortality rate was 4.7% (1/21 dogs) and median survival time was 554 days for the six patients with known dates of death. One- and two-year survival rates were 61% and 42%, respectively. This is the largest collection of carotid body paraganglioma cases reported in veterinary literature. Based on these results, surgical resection of carotid body paragangliomas was associated with low perioperative mortality and long survival times.

Evaluating machine learning model bias and racial disparities in non-small cell lung cancer using SEER registry data.

Despite decades of pursuing health equity, racial and ethnic disparities persist in healthcare in America. For cancer specifically, one of the leading observed disparities is worse mortality among non-Hispanic Black patients compared to non-Hispanic White patients across the cancer care continuum. These real-world disparities are reflected in the data used to inform the decisions made to alleviate such inequities. Failing to account for inherently biased data underlying these observations could intensify racial cancer disparities and lead to misguided efforts that fail to appropriately address the real causes of health inequity. Estimate the racial/ethnic bias of machine learning models in predicting two-year survival and surgery treatment recommendation for non-small cell lung cancer (NSCLC) patients. A Cox survival model, and a LOGIT model as well as three other machine learning models for predicting surgery recommendation were trained using SEER data from NSCLC patients diagnosed from 2000-2018. Models were trained with a 70/30 train/test split (both including and excluding race/ethnicity) and evaluated using performance and fairness metrics. The effects of oversampling the training data were also evaluated. The survival models show disparate impact towards non-Hispanic Black patients regardless of whether race/ethnicity is used as a predictor. The models including race/ethnicity amplified the disparities observed in the data. The exclusion of race/ethnicity as a predictor in the survival and surgery recommendation models improved fairness metrics without degrading model performance. Stratified oversampling strategies reduced disparate impact while reducing the accuracy of the model. NSCLC disparities are complex and multifaceted. Yet, even when accounting for age and stage at diagnosis, non-Hispanic Black patients with NSCLC are less often recommended to have surgery than non-Hispanic White patients. Machine learning models amplified the racial/ethnic disparities across the cancer care continuum (which are reflected in the data used to make model decisions). Excluding race/ethnicity lowered the bias of the models but did not affect disparate impact. Developing analytical strategies to improve fairness would in turn improve the utility of machine learning approaches analyzing population-based cancer data.

Clinical Characteristics and Outcomes in Patients with Ruptured Middle Cerebral Artery Aneurysms: A Multicenter Study in Northern China.

The long-term prognosis of ruptured middle cerebral artery aneurysms (MCAAs) in northern China remains unclear. The aim of this study is to analyze the epidemiological characteristics and long-term outcomes of ruptured MCAAs in northern China. We included patients who were consecutively admitted for ruptured MCAAs to 12 tertiary care centers in northern China from January 2017 to December 2020. Kaplan‒Meier curves were used to compare survival in hazard strata. The Cox proportional hazards model was used to analyze risk factors and mortality risk, whereas logistic regression was used to identify factors influencing 2-year survival. Subgroup analyses were performed to verify the robustness of the results. Data on 959 patients with ruptured MCAAs were analyzed; 16.4% of these patients had ruptured intracranial aneurysms (RIAs) and were registered in the Chinese cerebral aneurysm database. The mean follow-up duration was 3.0years (range 0-6.2years). The 3-month and 2-year mortality rates were 15.5% and 18.2%, respectively. The risk factors for mortality were identified via Cox regression and were as follows: age > 70years, previous stroke, combined intracerebral hemorrhage (ICH)/intraventricular hemorrhage (IVH), poor Hunt and Hess grade, multiple aneurysms, and conservative treatment (CT). The positive association between the risk of death and CT was consistent across subgroups. According to logistic regression, hypertension, previous stroke, combined ICH/IVH, Hunt and Hess grade, and WFNS (World Federation of Neurological Surgeons) score were identified as factors negatively influencing 2-year survival. We detail the epidemiologic characteristics and long-term outcomes of MCAAs. The risk factors for mortality included age > 70years, previous stroke, combined ICH/IVH, poor Hunt and Hess grade, and multiple aneurysms. Compared with microsurgical treatment (MST), CT is associated with an increased risk of mortality, while the risk of mortality associated with endovascular treatment (EVT) is not significantly different. Two-year survival was associated with hypertension, previous stroke, ICH/IVH, and poor grades at admission.

PD-1 blockade plus cisplatin-based chemotherapy in patients with small cell/neuroendocrine bladder and prostate cancers

Small cell neuroendocrine cancers share biologic similarities across tissue types, including transient response to platinum-based chemotherapy with rapid progression of disease. We report a phase 1b study of pembrolizumab in combination with platinum-based chemotherapy in 15 patients with stage III-IV small cell bladder (cohort 1) or small cell/neuroendocrine prostate cancers (cohort 2). Overall response rate (ORR) is 43% with two-year overall survival (OS) rate of 86% (95% confidence interval [CI]: 0.63, 1.00) for cohort 1 and 57% (95% CI: 0.30, 1.00) for cohort 2. Treatment is tolerated well with grade 3 or higher adverse events occurring in 40% of patients with no deaths or treatment cessation secondary to toxicity. Single-cell and Tcell receptor sequencing of serial peripheral blood samples reveals clonal expansion of diverse Tcell repertoire correlating with progression-free survival. Our results demonstrate promising efficacy and safety of this treatment combination and support future investigation of this biomarker. This study was registered at ClinicalTrials.gov (NCT03582475).

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma.

Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC. Medical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria. Total 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506). NAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Residual tricuspid regurgitation after transcatheter tricuspid valve edge-to-edge repair: the EuroTR Registry

Abstract Background Data on the prognostic impact of residual tricuspid regurgitation (TR) after transcatheter tricuspid valve edge-to-edge repair (T-TEER) are scarce. Purpose The aim of this analysis was to evaluate two-year survival and symptomatic outcomes of patients in relation to residual TR after T-TEER. Methods Using the large European Registry of Transcatheter Repair for Tricuspid Regurgitation (EuroTR Registry) we investigated the impact of residual TR on two-year all-cause mortality and New York Heart Association (NYHA) functional class at follow-up. The study further identified predictors for residual TR ≥3+ using a logistic regression model. Results The study included a total of 1286 T-TEER patients (53.6% females, mean age 78.0 ± 8.9 years). TR was successfully reduced to ≤1+ in 42.4%, 2+ in 40.0% and 3+ in 14.9% of patients at discharge, while 2.8% remained with TR ≥4+ after the procedure. Residual TR ≥3+ was an independent multivariable predictor of two-year all-cause mortality (hazard ratio 2.06, confidence interval 1.30-3.26, p=0.002, Figure 1). The prevalence of residual TR ≥3+ was 4-times higher in patients with higher baseline TR (vena contracta &amp;gt; 11.1 mm) and more severe TV tenting (tenting area &amp;gt;1.92 cm2) (Figure 2). Of note, no survival difference was observed in patients with residual TR ≤1+ vs. 2+ (76.2% vs. 73.1%, p=0.461). The rate of NYHA functional class ≥ III at follow-up was significantly higher in patients with residual TR ≥3+ (52.4% vs. 40.5%, p&amp;lt;0.001). Of note, the degree of TR reduction significantly correlated with the extend of symptomatic improvement (p=0.012). Conclusions T-TEER effectively reduced TR severity in the majority of patients. While residual TR ≥3+ was associated with worse outcomes, no differences were observed for residual TR 1+ vs. 2+. Symptomatic improvement correlated with the degree of TR reduction.Figure 1- Residual TR after T-TEERFigure 2 - Predicting residual TR

When does annual geriatric hip fracture mortality revert to baseline?

Geriatric hip fracture patients exhibit high mortality post-injury. It's unclear if and when mortality reverts to baseline. We therefore ask, When, if ever, does the mortality rate of geriatric hip fracture revert to the population-wide baseline rate? How does the mortality rate after geriatric hip fracture compare to the population norms? Understanding this timeline is crucial for assessing disease burden and guiding treatment plans. A cohort of 17,868 male patients aged 65-89 years treated for hip fracture within the VA healthcare system was studied. Patients were grouped by age at the time of fracture, and age-specific fractional survival was assessed annually for 10 years. For a comparison control group, a virtual cohort of 17,868 individuals, mirroring the age distribution of the patient group, was created and reduced over 10 cycles according to Social Security Administration expected mortality statistics. The year-one mortality rate among fracture patients was 35.4%, compared to 6.3% in age-matched controls. By year ten, only 8.5% of the fracture patients remained alive, vs. 39.8% in the general population. The annual risk of dying for patients who survived past the first year was consistently in the range 19%-21% for all subsequent years. Hip fracture patients who survive the initial injury are still subject to annual mortality risk of approximately 20%, an elevation above population norms persisting for at least a decade. The data underscores the severity of geriatric hip fractures, and suggest that focusing one- or two-year survival rates may not fully capture the severity of the injury.

Outcomes among Patients with End-Stage Kidney Disease and Chronic Limb-Threatening Ischemia: A Population-based Cohort Study.

To understand mortality and secondary outcomes in patients with both end-stage kidney disease (ESKD) and chronic limb-threatening ischemia (CLTI) after no procedural treatment, primary amputation, endovascular treatment, and open surgery. ESKD and CLTI commonly cooccur and limited prior work has demonstrated poor outcomes including one-year survival despite treatment. We conducted a retrospective national cohort study of United States Renal Data System data from January 1, 2016 to December 31, 2019 to determine mortality, major postoperative complications, and other outcomes. We performed an exploratory analysis comparing two-year survival by treatment using propensity matching. Of 1,876,652 records with a CLTI diagnosis, we identified 3,908 patients with ESKD and an incident CLTI diagnosis. Mean age at CLTI diagnosis was 65.7 years and 2,405 (61.5%) were male. 2,696 (69.0%) had no procedural treatment, 609 (15.6%) had major limb amputation, 439 (11.2%) had endovascular treatment, and 164 (4.2%) had open surgery. There was 44.9% mortality at one year, along with 41.8% major postoperative complications and 52.6% readmissions at 90 days. Comparing two-year survival, we found no differences between the amputation and endovascular cohorts (P=0.08) and between endovascular and open (P=.06). There was superior two-year survival in the open surgery cohort compared to the amputation cohort (P=0.002). Patients living with both ESKD and CLTI experience poor outcomes irrespective of treatment. Exploratory analyses demonstrated that two-year survival among the three principal procedural treatments was similar except for superior survival among patients undergoing open therapy compared to primary amputation.

Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.

Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.

Single- Versus Triple-Agent Intra-Arterial Chemotherapy for Retinoblastoma

To compare the ocular and systemic outcomes of single- (melphalan) versus triple-agent (melphalan, topotecan, carboplatin) intra-arterial chemotherapy (IAC) for retinoblastoma (RB) eye salvage. Retrospective single-institutional clinical cohort study. Children <18 years with RB who underwent one or more IAC procedures between 2016 and 2024 with minimum 6-month follow-up were reviewed. Data included clinical features, IAC procedural details, additional eye-saving treatments, complications, and follow-up. Primary outcomes included ocular and systemic complications of IAC, intraocular recurrence, extraocular extension, metastasis, and death. Secondary outcomes were tumor response, ocular survival, and recurrence-free ocular survival. Comparative analysis was performed for single- versus triple-agent groups. A SWIMMERrb plot graphically illustrated additional treatments following IAC. Thirty-eight eyes of 37 children (24 unilateral RB) were reviewed. Two eyes (2 children) had single- followed by multi-agent IAC and were excluded. Of 35 included children, one had bilateral triple-agent IAC. IAC (median, 3 doses; range, 1-4) was employed as primary (n=21 eyes) or secondary (n=15 eyes) treatment. Chemotherapy was single-agent in 13 eyes and triple-agent in 23 eyes. Following IAC, 25 eyes required additional eye-saving treatments (69% single- v 70% triple-agent, p=0.983). At final follow-up, the triple-agent group was more likely to achieve very good partial or complete tumor response (91% v 62%, p=0.030). Two-year recurrence-free ocular survival was 63.3% (95% CI 45.7-80.9), similar for both groups (p=0.700). Globe salvage was 72%. Two-year ocular survival was 72.2% (95% CI 57.2-87.2), higher for the triple-agent group (82.6% v 53.8%; p=0.059). Ocular complications occurred in 31% of eyes in the single- and 52% of eyes in the triple-agent group (p=0.215). The rate of systemic complications was 38% v 74% in the single- versus triple-agent groups, respectively (p=0.036). No extraocular extension, metastasis, or death were observed at median 34.2 months (range, 14.5-87.0) follow-up. Triple-agent IAC was associated with improved RB tumor response and ocular survival, though similar recurrence-free ocular survival compared to single-agent. While there were more complications with triple-agent IAC, most were mild or transient.