5-year Patient Survival Research Articles

Improved Outcomes and Resource Use With Normothermic Machine Perfusion in Liver Transplantation.

Normothermic machine perfusion (NMP) has been shown to reduce peritransplant complications. Despite increasing NMP use in liver transplant (LT), there is a scarcity of real-world clinical experience data. To compare LT outcomes between donation after brain death (DBD) and donation after circulatory death (DCD) allografts preserved with NMP or static cold storage (SCS). This single-center, retrospective observational cohort study included all consecutive adult LTs performed between January 2019 and December 2023 at the Mayo Clinic in Arizona. Data analysis was performed between February 2024 and June 2024. Outcomes of DBD-SCS, DBD-NMP, DCD-SCS, and DCD-NMP transplants were compared. DBD and DCD livers preserved on NMP or SCS. The primary outcomes were early allograft dysfunction (EAD), intraoperative transfusion, and post-LT hospital resource use, including length of stay (LOS) and readmissions. Secondary outcomes included acute kidney injury (AKI) and 1-year graft and patient survival. A total of 1086 LTs were included in the following 4 groups: DBD-SCS (n = 480), DBD-NMP (n = 63), DCD-SCS (n = 264), and DCD-NMP (n = 279). Among LT recipients, median (IQR) age was 60.0 years (52.0-66.0); 399 LT recipients (36.7%) were female. DCD-NMP had the lowest EAD rate (17.5%), followed by DCD-SCS (50.0%), DBD-NMP (36.8%), and DBD-SCS (27.3%) (P < .001). DCD-NMP had the lowest intraoperative transfusion requirement compared to all other groups. Hospital and intensive care unit (ICU) LOS were shortest in DCD-NMP (median [IQR] hospital LOS, 5.0 days [4.0-7.0]; P = .01; median [IQR] ICU LOS, 1.5 days [1.2-3.1]; P = .01). One-year cumulative readmission probability was 86% lower for DCD-NMP vs DCD-SCS (95% CI, 0.09-0.22; P < .001) and 53% lower for DBD-NMP vs DBD-SCS (95% CI, 0.26-0.87; P < .001). AKI events were lower in DCD-NMP (31.1%) vs DCD-SCS (47.4%) (P = .001). Compared to SCS, the NMP group had a 78% overall reduction in graft failure (hazard ratio [HR], 0.22; 95% CI, 0.10-0.49; P < .001). For those receiving DCD allografts, the risk reduction was even more pronounced, with an 87% decrease in graft failure (HR, 0.13; 95% CI, 0.05-0.33; P < .001). NMP was significantly protective from patient mortality vs SCS (HR, 0.31; 95% CI, 0.12-0.80; P = .02). In this observational high-volume cohort study, NMP significantly improved LT clinical outcomes and reduced hospital resource use, especially in DCD allografts. NMP may enhance access to LT by addressing the challenges historically linked with DCD liver use.

Development of a Nomogram and Risk Grouping System for Predicting 1-Year Overall Survival of Patients With Atypical Teratoid/Rhabdoid Tumors.

Atypical teratoid/rhabdoid tumor (AT/RT) is a kind of central nervous system malignant tumor in children. In this study, we aimed to develop a practically clinical nomogram and risk grouping system to predict 1-year overall survival for patients with atypical teratoid/rhabdoid tumor. The nomogram was constructed based on the pediatric tumor registry of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. Fifty-four information-integrated patients with atypical teratoid/rhabdoid tumor were included from the database. Cox regression analyses were used to select independent prognostic factors. Based on the fitted multivariate Cox regression model, a nomogram of 1-year overall survival for atypical teratoid/rhabdoid tumor patients was generated. Moreover, the nomogram was validated by assessing its discrimination and calibration. In these patients, age at diagnosis, the extent of tumor resection, radiotherapy, and chemotherapy were included in the multivariate Cox regression model. Based on this multivariate Cox regression model, a nomogram of 1-year overall survival for atypical teratoid/rhabdoid tumor patients was generated. The nomogram had good discrimination (the concordance index was 0.781) and calibration curves showed no deviation from reference lines. Decision curve analysis demonstrated this nomogram was useful for clinical practice. The risk grouping system was built based on nomogram-derived risk scores, which could classify patients into 3 risk groups. Compared with the low-risk group, the risk of 1-year death was significantly higher in the intermediate-risk group (hazard ratio = 1.42, 95%, confidence intervals = 0.49-4.11) and high-risk group (hazard ratio = 9.78, 95% confidence intervals = 3.53-27.1). A nomogram and risk grouping system were built to predict for the 1-year overall survival of atypical teratoid/rhabdoid tumor patients. The nomogram could facilitate a personalized prognostic evaluation for atypical teratoid/rhabdoid tumor patients and help medical practitioners make better treatment.

Overexpression of PLCG2 and TMEM38A inhibit tumor progression in clear cell renal cell carcinoma

Clear cell renal cell carcinoma is a prevalent urological malignancy, imposing substantial burdens on both patients and society. In our study, we used bioinformatics methods to select four putative target genes associated with EMT and prognosis and developed a nomogram model which could accurately predicting 5-year patient survival rates. We further analyzed proteome and single-cell data and selected PLCG2 and TMEM38A for the following experiments. Overexpression models of PLCG2 and TMEM38A were generated in Caki-1 and 786-O cell lines using plasmids. The in vitro experiments demonstrated that both of them exerted pro-apoptotic effects on Caki-1 and 786-O cells, inducing G2/M phase arrest, inhibiting proliferation, and suppressing EMT. In summary, we identified potential tumor suppressor factors and stratified ccRCC patients into high-risk and low-risk groups based on these factors. Furthermore, we elucidated the impact of PLCG2 and TMEM38A in Caki-1 and 786-O cell lines, offering novel avenues for therapeutic target exploration.

Digital Profiling of Immune Biomarkers in Breast Cancer: Relation to Anthracycline Benefit.

Assessment of the tumor immune microenvironment can be used as a prognostic tool for improved survival and as a predictive biomarker for treatment benefit, particularly from immune modulating treatments including cytotoxic chemotherapy. Using Digital Spatial Profiling (DSP), we studied the tumor immune microenvironment of 522 breast cancer cases by quantifying 35 immune biomarkers on tissue microarrays from the MA.5 phase III clinical trial. In this trial, node-positive breast cancer patients were randomized to receive either a non-anthracycline chemotherapy (CMF) or anthracycline-containing cytotoxic chemotherapy (CEF). Donor block hematoxylin and eosin (H&E)-stained sections were scored for the level of stromal tumor infiltrating lymphocytes (sTILs), according to the international guidelines. We hypothesized that patients with higher levels of tumor immune infiltration, assessed by either DSP or H&E staining, would benefit from CEF (relative to CMF) more than patients with lower immune infiltration. Unsupervised hierarchical clustering of digitally scored biomarkers revealed two patient clusters: immune infiltrated vs. ignored. Following a pre-specified statistical plan crafted to meet ReMARK guidelines, we found that the DSP-derived Immune Cluster assignment did not predict an improved 10-year relapse-free survival for patients receiving CEF compared to CMF. However, a secondary hypothesis revealed a significant predictive value for H&E-sTILs assessed on full-faced sections for CEF benefit over CMF in the entire cohort and the HER2-enriched subset. As exploratory analyses, supervised clustering of DSP scored biomarkers suggested that low levels of TIM-3 and high levels of HLA-DR and PD-L1 are associated with sensitivity to CEF. Although novel high-plex techniques provide a detailed insight into the tumor microenvironment, conventional H&E staining remains a powerful tool that can be applied onto full-faced sections to assess the value of immune microenvironment, particularly sTILs, in predicting benefits from immunogenic chemotherapies.

Insufficient pretransplant induction therapy is associated with diffuse intrahepatic cholangiopathy in ABO-incompatible living donor liver transplantation for acute liver failure.

ABO-incompatible liver transplantation (ABOi LT) can now be successfully performed with standard pretransplant induction therapy. For patients with chronic end-stage liver disease (ESLD), ABOi LT can achieve long-term outcomes comparable to those of blood type-compatible (ABOc) LT. Outcomes of patients with acute liver failure (ALF) who undergo urgent transplantation surgery with a limited induction period should be further investigated. Between 2004 and 2023, adult patients who underwent living donor liver transplantation (LDLT) at Taipei Veterans General Hospital were enrolled. Based on the chronicity of liver disease and the transplant type, patients were divided into 4 groups for outcome analysis: ALF patients who received ABOi LDLT, ALF patients who received ABOc LDLT, ESLD patients who received ABOi LDLT, and ESLD patients who received ABOc LDLT. Four instances of diffuse intrahepatic cholangiopathy (DIC) occurred in the ABOi LDLT group (n=3, 27.3% in group 1 and n=1, 2.6% in group 3, p=0.03). In ABOi LDLT patients, rituximab was administered closer to LT in group 1 (5 [3~6] days before LDLT) than that in group 3 (15 [14~22] days before LDLT) (p<0.01). Univariate analysis revealed that ALF, small graft-to-recipient weight ratio (GRWR), low rituximab dose (<210 mg/m 2) and postoperative rebound of isoagglutinin immunoglobulin M (IgM) antibody titers were factors contributing to an increased risk of DIC. Allograft loss eventually occurred in 3 of the 4 patients with DIC. Overall, ABOi LDLT showed inferior long-term outcomes for ALF (5-year patient survival: 62.3%/73.6%/74.1%/76.7% in groups 1/2/3/4, respectively, p=0.25). ABOi LDLT achieved outcomes comparable to those of ABOc LDLT among ESLD patients but not among ALF patients. DIC results in a high risk of allograft loss; however, the combination of potent immunosuppressive agents and early recognition of antibody rebound and the initiation of salvage treatment may improve long-term outcomes among these patients.

An oral microbiota-based deep neural network model for risk stratification and prognosis prediction in gastric cancer

ABSTRACT Background This study aims to develop an oral microbiota-based model for gastric cancer (GC) risk stratification and prognosis prediction. Methods Oral microbial markers for GC prognosis and risk stratification were identified from 99 GC patients, and their predictive potential was validated on an external dataset of 111 GC patients. The identified bacterial markers were used to construct a Deep Neural Network (DNN) model, a Random Forest (RF) model, and a Support Vector Machine (SVM) model for predicting GC prognosis. Results GC patients with <3 years of survival showed a higher abundance of Aggregatibacter and diminished abundances of Filifactor and Moryella than those who survived ≥3 years. The Boruta algorithm unearthed Leptotrichia as another significant marker for GC prognosis. Consequently, a DNN model was constructed based on the relative abundances of these bacteria, predicting 3-year and 5-year survival in GC patients with Area Under Curve of 0.814 and 0.912, respectively. Notably, the DNN model outperformed the TNM staging system, SVM and RF models. The prognostic value of these bacterial markers was further reinforced by external validation. Conclusion The oral microbiota-based DNN model may advance GC prognosis. The biological functions of these oral bacterial markers warrant further investigation from the perspective of GC progression.

Gender Differences Are a Leading Factor in 5-Year Survival of Patients with Idiopathic Pulmonary Fibrosis over Antifibrotic Therapy Reduction.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease with a median survival of 3-5 years. Antifibrotic therapies like pirfenidone and nintedanib slow progression, but the outcomes vary. Gender may influence disease presentation, progression, and response to treatment. This study evaluates the impact of gender on the 5-year survival, pharmacological management, and clinical outcomes of patients with IPF. A retrospective cohort study of 254 IPF patients was conducted, with 164 (131 males:33 females) having complete data. Patients underwent spirometry, DLCO, and 6 min walk tests. Data on comorbidities, smoking, antifibrotic therapy type, dosage adjustments, and adverse events were collected. We used Kaplan-Meier survival curves and logistic regression to assess gender-related differences in outcomes. Men had worse lung function at diagnosis (FVC 74.9 ± 18.5 vs. 87.2 ± 20.1% of pred.; p < 0.001) and a higher smoking prevalence (74% vs. 30%; p < 0.001). Women had better survival (51.2 vs. 40.8 ± 19.2 months; p = 0.005) despite more frequent biopsy use (36% vs. 17%; p = 0.013). Women tolerated longer therapy better (p = 0.001). No differences were found between patients receiving reduced antifibrotic dosing and those receiving full dosing. Gender has a significant impact on IPF outcomes, with women demonstrating better survival and tolerance to long-term therapy. In contrast, reducing antifibrotic treatment does not appear to significantly affect survival outcomes. These findings underscore the need for future research on gender-specific management approaches.

Comparing multi-texture fibrosis analysis versus binary opacity-based abnormality detection for quantitative assessment of idiopathic pulmonary fibrosis

Automated tools for quantification of idiopathic pulmonary fibrosis (IPF) can aid in ensuring reproducibility, however their complexity and costs can differ substantially. In this retrospective study, two automated tools were compared in 45 patients with biopsy proven (12/45) and imaging-based (33/45) IPF diagnosis (mean age 74 ± 9 years, 37 male) for quantification of pulmonary fibrosis in CT. First, a tool that identifies multiple characteristic lung texture features was applied to measure multi-texture fibrotic lung (MTFL) by combining the amount of ground glass, reticulation, and honeycombing. Opacity-based fibrotic lung (OFL) was measured by a second tool that performs a simpler binary classification of tissue into either normal or opacified lung and was originally developed for quantifying pneumonia. Differences in quantification of MTFL and OFL were assessed by Mann-Whitney U-test and Pearson correlation (r). Also, correlation with spirometry parameters (percent predicted total lung capacity (TLC), percent predicted vital capacity (VC), percent predicted forced expiratory volume in 1 s (FEV1), diffusing capacity of the lungs for carbon monoxide (DLCO), partial pressure of oxygen (PO2) and carbon dioxide (PCO2)) were assessed by r. The prognostic values for 3-year patient survival of OFL, LSS and MTFL were investigated by multivariable Cox-proportional-hazards (CPH) models including sex, age and TLC and including sex, age and VC. Also, Kaplan-Meier analysis with log rank test between subgroups separated by median OFL and MTFL were conducted. No significant difference between OFL and MTFL was observed (median and interquartile range: OFL = 29% [20-38%], MTFL = 31% [19-45%]; P = 0.44). For OFL significant correlation was observed to MTFL (r = 0.93, P < 0.01) and VC (r=-0.50, P = 0.03). For MTFL no significant correlation to spirometry parameters was found. The total time for one analysis was lower for the automated MTFL (MTFL: 313 ± 25s vs. OFL: 612 ± 61s, P < 0.001). Both analyses were significant predictors in the multivariable CPH analysis including TLC (hazard-ratios: MTFL 1.03 [1.01–1.06], P = 0.02; OFL 1.03 [1.00-1.06], P = 0.03). No parameter was a significant predictor in the CPH models including VC (hazard-ratios: MTFL 1.01 [0.98–1.04], P = 1; OFL 1.01 [0.97–1.05], P = 1). OFL showed significance in Kaplan-Meier analysis (MTFL: P = 0.17; OFL: P = 0.03). Using a simple opacity-based quantification of pulmonary fibrosis in IPF patients displayed similar results and prognostic value compared to a more complex multi-texture based analysis.

Survival analysis of patients with hepatocellular carcinoma based on the ratio of platelet count to spleen diameter.

In China, 80% of Hepatocellular Carcinoma (HCC) is associated with cirrhosis. Portal hypertension, the most common outcome of cirrhosis progression, has a high incidence. Platelet count/spleen diameter ratio (PSL) with a cut-off value of 909 can predict the presence of esophagogastric varices and thus portal hypertension, which is also an independent risk factor for early recurrence and late recurrence of hepatocellular carcinoma after resection. Therefore, the effect of PSL on the overall survival (OS) of patients with HCC is necessary. The aim of this study was to apply a new method to establish and validate a model for predicting the prognosis of patients based on PSL with HCC. A total of 1,104 patients with clinical diagnosed with HCC following non-surgical therapy randomly divided the patients into a primary cohort and a validation cohort in a ratio of 7:3, in which 772 HCC patients were in the primary cohort and a total of 332 HCC patients were in the validation cohort. Through Lasso-Cox analysis, the independent predictors of OS of training cohort were included in nomogram1, and the independent predictors of Cox regression analysis were included in nomogram2. Nomogram1 and nomogram2 used consistency index (C-index), AUC and time-dependent ROC curves in the training cohort, respectively, and the calibration curves were plotted. All suggest that nomogram1 is better than nomogram2. We get similar results in the validation cohort. The C-index of nomogram1was 0.792 (95%CI: 0.772-0.812), which was superior to nomogram2 (0.788) and traditional modes (0.631-0.712). The AUC of nomogram1 was 0.866 (95%CI: 0.840-0.889). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.769, 95%CI: 0.740-0.798; AUC: 0.867, 95%CI: 0.826-0.902). Calibration plots for 3-year OS probabilities showed the good agreement between nomogram1 predictions and actual observations. In addition, we found that the decision curve analysis of nomogram1 and nomogram2 was also meaningful. Novel nomogram containing PSL, based on LASSO Cox regression, had higher predictive efficacy for 3-year overall survival in patients with HCC.

Development and validation of a machine learning-based model to predict survival in patients with cirrhosis after transjugular intrahepatic portosystemic shunt

Although numerous prognostic scores have been developed for patients with cirrhosis after Transjugular intrahepatic portosystemic shunt (TIPS) placement over years, an accurate machine learning (ML)-based model remains unavailable. The aim of this study was to develop and validate a ML-based prognostic model to predict survival in patients with cirrhosis after TIPS placement. In this retrospective study in China, patients diagnosed with cirrhosis after TIPS placement from 2014 to 2020 in our cohort were included to develop a ML-based model. Patients from the other two tertiary hospitals between 2016 and 2022 were as external validation cohort. The random forest (RF) model was built using 7 selected features via the least absolute shrinkage and selection operator (LASSO) regression, and subsequent 10-fold cross-validation was performed. A total of 400 patients in our cohort were included (median age and interquartile range, 59 (50, 66); 240 men). Two hundred and eighty patients made up the training set and 120 were in the testing set, and 346 patients were included in the external validation cohort. Seven attributes were selected: Na, ammonia (Amm), total bilirubin (Tb), albumin (Alb), age, creatinine (Cr), and ascites. These parameters were included in a new score named the RF model. The accuracy, precision, recall, and F1 Score of the RF model were 0.84 (95% CI: 0.76, 0.91), 0.84 (95% CI: 0.77, 0.91), 0.99 (95% CI: 0.95, 1.00), 0.91 (95% CI: 0.81, 0.10) in the testing set, and 0.88 (95% CI: 0.84, 0.91), 0.89 (95% CI: 0.85, 0.92), 0.99 (95% CI: 0.97, 1.00), 0.93 (95% CI: 0.85, 0.97) in the validation cohort, respectively. The calibration curve showed a slope of 0.875 in the testing set and a slope of 0.778 in the external validation cohort, suggesting well calibration performance. The RF model outperformed other scoring systems, such as the (Child-Turcotte-Pugh score) CTP, (model for end-stage liver disease) MELD, (sodium MELD) MELD-Na, (Freiburg index of post-TIPS survival) FIPS and (Albumin-Bilirubin) ALBI, showing the highest (area under the curve) AUC of 0.82 (95% CI: 0.72, 0.91) and 0.7 (95% CI: 0.60, 0.79) in predicting 1-year survival across the testing set and external validation cohort. This study developed a RF model that better predicted 1-year survival for patients with cirrhosis after TIPS placement than the other scores. National Natural Science Foundation of China (grant numbers 81900552 and 82370628).

Plasmapheresis, immunosuppressive therapy and anti-GBM disease prognosis: a cohort study of 107 patients

Background Anti-glomerular basement membrane (anti-GBM) disease presents with rapidly progressive glomerulonephritis and alveolar hemorrhage, requiring urgent management. In this study, we analyzed the relationship between plasmapheresis strategy, immunosuppressive therapy and the prognosis of anti-GBM disease patients. Method We screened newly diagnosed anti-GBM disease patients at West China Hospital of Sichuan University from 2010 to 2021. The primary outcome was a composite endpoint of in-hospital death or dialysis dependency upon discharge. Results This study enrolled 107 anti-GBM disease patients. The use of plasmapheresis was independently associated with a reduced risk of primary outcome (OR: 0.179, 95% Cl: 0.051–0.630, p = 0.007), better 2-year (HR: 0.146; 95% CI: 0.038–0.553; p = 0.005) and 8-year patient survival (HR: 0.309; 95% CI: 0.112–0.850; p = 0.023). Restricted cubic spline regression suggested that patients with 5–10 sessions of plasmapheresis had already achieved maximum risk reduction in the primary outcome. Patients who started plasmapheresis at lower serum creatinine (42.9% vs. 96.2%, p < 0.001) or lower anti-GBM antibody levels (44.4% vs. 93.3%, p = 0.030) had lower risk of primary outcome than those at higher levels. Use of high-dose methylprednisolone (p = 0.505), pulsed cyclophosphamide (p = 0.343) or ANCA positivity (p = 0.115) were not related to primary outcome in anti-GBM disease. Conclusion Plasmapheresis was protective for both in-hospital outcome and long-term survival in anti-GBM disease. Patients who initiated plasmapheresis early had a better prognosis and might only need 5–10 plasmapheresis sessions to achieve maximal risk reduction. Use of high-dose methylprednisolone or cyclophosphamide pulses was not related to improved short- or long-term outcomes in anti-GBM disease.

Oligometastatic Disease Is Not an Absolute Contraindication to Pelvic Exenteration in Selected Patients With Locally Recurrent Rectal Cancer.

The treatment of locally recurrent rectal cancer has evolved dramatically in recent decades. As the boundaries of exenterative surgery continue to be pushed, one of the unanswered and controversial questions is the role of radical salvage surgery for locally recurrent rectal cancer in the setting of oligometastatic disease. To investigate the impact of synchronous or previously treated distant metastases on survival following pelvic exenteration for locally recurrent rectal cancer. Retrospective analysis of a prospectively maintained database. A high-volume specialist exenteration center. Consecutive adult patients undergoing pelvic exenteration with curative intent for locally recurrent rectal cancer between 1994 and 2023. Overall survival from time of pelvic exenteration. Of the 300 patients included, 193 (64%) were male and the median age was 62 years (range, 29-86). Median time from primary rectal cancer surgery to pelvic exenteration was 35 months (range, 4-191). In total, 56 patients (19%) had a history of metastatic disease; of which 42 (14%) had previously treated metastases and 18 patients (6%) had synchronous metastatic disease (including 4 patients with both synchronous and previously treated metastases). Five-year and median overall survival was 41% and 45 months, respectively. There was a trend toward poorer 5-year overall survival in patients with a history of metastatic disease compared to those without (25% vs 45%); however, this did not reach statistical significance (p = 0.110), possibly due to lack of statistical power. Five-year overall survival was 27%, 25% and 45% for patients with synchronous metastases, previously treated metastases, and no history of metastases, respectively (p = 0.260). Findings may not be applicable beyond highly selected patients treated at specialized exenteration centers. Long-term survival is achievable in highly selected patients with locally recurrent rectal cancer and synchronous or previously treated distant metastases. Therefore, oligometastatic disease should not be considered an absolute contraindication to exenterative surgery. See Video Abstract.

Neoadjuvant atezolizumab + chemotherapy for resectable NSCLC: 3-year clinical update of phase II clinical trial results and translational findings.

Neoadjuvant chemoimmunotherapy has achieved overall survival (OS) benefit for patients with resectable non-small cell lung cancer (NSCLC). Here, we present outcomes after 3 years of follow-up from the first reported study of neoadjuvant atezolizumab+chemotherapy. This open-label, multicenter single-arm investigator-initiated phase II study conducted at three US hospitals tested up to four cycles of atezolizumab, carboplatin, and nab-paclitaxel prior to surgery. Major pathological response (MPR, primary endpoint) was previously reported; here, we report 3-year disease-free survival (DFS), OS, and clinical characteristics of patients developing brain metastases (BM) with integrated data from tumor genomics, gene expression, and quantitative immunofluorescent measurement of immune markers. Of 30 enrolled patients, 29 were taken to the operating room. 26 underwent R0 resection, with 17 experiencing MPR (10 pCR). With a median follow-up of 39.5 months, the median OS was 55.8 months, and the median DFS was 34.5 months. Landmark OS at 36 months was 77%. Among 14 patients with recurrent disease, 6 patients had BM. Patients whose tumors had mutations in STK11 and KEAP1 did not have a significantly higher incidence of BM. Reduced copy number of STK11 and KEAP1, both residing on chromosome 19p, was observed in ~1/3 of tumors. Reduced CN of STK11 was significantly associated with worse pathological response and incidence of BM. Consistent with recent phase III studies, 3-year OS data with neoadjuvant atezolizumab+chemotherapy was associated with prolonged PFS and OS. Establishing associations between STK11 and KEAP1 genomic alterations and key clinical outcomes in early-stage NSCLC requires further study.

New Immunosuppressants in Pediatric Kidney Transplantation: What's in the Pipeline for Kids?

The 1- and 5-year patient and graft survival rates of pediatric kidney transplant recipients have improved considerably in recent years. Regardless of early success, kidney transplantation is challenged by suboptimal long-term allograft and patient survival. Many kidney transplants are lost due to immune (rejection) and nonimmune allograft injuries, and patient survival is limited from cardiovascular disease, infection, and malignancy. Many of these co-morbidities are due to side effects of the currently available immunosuppressive drugs, especially calcineurin inhibitors and glucocorticoids, which are associated with long-term toxicity. Hence, there is an urgent need to develop new, more specific and less toxic immunosuppressive drugs. Unfortunately, there have also been no new drug approvals for adult kidney transplant recipients since belatacept in 2012, leaving the immunosuppressive drug armamentarium unchanged for more than 20 years. As a consequence of the lack of innovation in adult kidney transplant recipients, the pipeline of novel immunosuppressive agents for pediatric solid organ transplant recipients is also limited. The most promising agent in the near future, at least for adolescent patients, appears to be belatacept, despite its many limitations. In this review article, we report on three areas that appear to be the most relevant topics at this time: (i) extended-release tacrolimus, (ii) costimulation blockade with belatacept, and (iii) treatment of antibody-mediated rejection. Improved synergies between the pharmaceutical industry and the transplant community are needed to achieve the ultimate goal of improving long-term outcomes in pediatric kidney transplantation.

Relative Survival, Conditional Survival, and Causes of Death in Patients with Early Gastric Cancer, with a Focus on Differences Between Cardia and Non-Cardia Cancer.

Background: Many researchers believe that cardia (CGC) and non-cardia (NCGC) are two different types of tumors, having different features like incidence rate, risk factors, geographical location, and socioeconomic status. This study aims to investigate the causes of death (COD) survival rates among early gastric cancer patients with a focus on differences between CGC and NCGC. Methods: This retrospective study employed SEER*stat software (version 8.3.92) to analyze the SEER 17 plus dataset (2000-2019). Standardized mortality ratios (SMR) were computed. Relative survival and conditional survival post-diagnosis were calculated using R software (version 4.1.0) among the different subgroups. Results: Within the follow-up period, 55.4% (5381) died, predominantly within the initial year post-diagnosis. Esophageal cancer was the leading non-gastric cancer cause in CGC, while miscellaneous tumors dominated in NCGC. The 1-year and 5-year relative survival for CGC patients were 76.4% and 48.9% respectively, while for NCGC were 80.4% and 63.9%. The 3-year conditional survival after 1 year and 5e years of survival for CGC were 68.7% and 88.8%, respectively, while for NCGC were 82.2% and 93.5%, respectively. This means that the longer a person has survived after diagnosis with cancer, the greater the likelihood that person will survive for another 3 years. Conclusions: This study sheds light on the substantial impact of non-cancer COD in GC patients, underscoring the necessity of considering comorbidities in their comprehensive management and follow-up. Impact: This study contributes valuable insights for clinical decision-making and informs future research directions regarding CGC and NCGC.

Impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period

AIM: assess the impact of neoadjuvant chemotargeted therapy in patients with colorectal cancer and synchronous liver metastases in perioperative period.PATIENTS AND METHODS: a pilot prospective study included 30 patients with colorectal cancer and synchronous liver metastases (mCRC). The combined treatment included 3 cycles of neoadjuvant FOLFOXIRI chemotherapy with the addition of targeted agents: cetuximab (24 patients with wtKRAS) and bevacizumab (6 patients with mtKRAS) followed by radical surgery.RESULTS: the clinical and radiological response of colorectal cancer liver metastases to neoadjuvant chemotherapy (NACT) was complete in 4 (13.3%) patients and partial in 26 (86.7%) patients. Partial response to NACT in the primary tumor occurred in all patients. Adverse events of NACT were detected in 12 (40%) patients, 1 (3.3%) of them produced grade III toxicity. All patients underwent radical surgery (R0) 3–4 weeks after NACT, 28 (93.3%) of them underwent simultaneous colorectal and liver resection. Postoperative complications occurred in 21 (70%) patients, including grade I and grade IIIa complications (according to Сlavien-Dindo classification) — 22 (73.3%) and 2 (6.7%), respectively. Histology revealed pathologic complete response (pCR) of liver metastases in 1 (3.6%) case and pathological grade 3 regression of the primary tumor (TRG3, Mandard A.M.) in 23 (76.7%) patients. Two (6.7%) patients with complete clinical and radiological response of liver metastases, who did not undergo liver resection, had no evidence of disease progression 12 months after the treatment.CONCLUSION: in mCRC with synchronous liver metastases, NACT according to the FOLFOXIRI regimen in combination with targeted agents with a moderate toxicity profile provide significant carcinocidal effect without having a negative impact in the perioperative period. The study is ongoing to analyze 2-year disease-free and overall survival of patients.

The optimal surgical time after stent placement in obstructive colorectal cancer: impact on long-term survival of patients.

To investigate the optimal interval between self-expanding metal stent (SEMS) placement and radical surgery in patients with obstructive colorectal cancer. In this study, a retrospective research design was used to select 125 patients with obstructive colorectal cancer who underwent colonoscopic SEMS placement with subsequent radical surgery between February 2011 and November 2022 at Shanghai Changhai Hospital. In addition, their clinical data and therapeutic efficacy were examined. Grouping: grouping on the basis of the interval of bridge to surgery (BTS). Group A: interval of BTS ≤ 14days; group B: 14days < interval of BTS ≤ 21days; group C1: interval of BTS > 21days; group C2: interval of BTS > 21days, excluding patients who received neoadjuvant therapy; group D: patients who received neoadjuvant therapy. Patients were grouped according to their different surgical methods, group E: patients who received open surgery and group F: patients undergoing laparoscopic surgery. A total of 125 patients were included in this study, the mean age of the patients was 61.34 ± 13.99years, with the median follow-up time was 39 (25-61) months. Of these, 84 cases (67.2%) underwent open surgery, while 41 cases (32.8%) underwent laparoscopic surgery. Among the cohort, 15 patients received neoadjuvant radiotherapy and chemotherapy after placement of SEMS. There was a significant difference in preoperative hemoglobin levels between group A and both group B and group C1. The laparoscopic surgery rate was significantly higher in group B than in the other two groups (48.57% versus 3.33% and 22.81%, P = 0.038). The 5-year disease-free survival (DFS) of group C1 patients was lower than that in group A and group B (32.4% versus 56.3%, 62.3%, P = 0.038; P = 0.043), whereas there was no statistical difference in the 5-year overall survival (OS) (60.7% versus 62.1%, 69.6%, P = 0.365, P = 0.339). group D showed a higher proportion of open surgery and a higher T-stage (P < 0.05), resulting in a 5-year DFS that was inferior to group A and group B (17.7% versus 56.3%, 62.3%, P = 0.045; P = 0.047). However, there was no significant difference compared with group C2 (17.7% versus 36.9%, P > 0.05). The 5-year OS of group D was not statistically significantly different from that of group A, group B, and group C2 (28.4% versus 62.1%, 69.6%, 73.4%, P = 0.089, P = 0.090, P = 0.183). In addition, no statistically significant differences were identified in 5-year DFS (49.9% versus 37.0%, P = 0.555) or 5-year OS (66.2% versus 62.6%, P = 0.062) between group E and group F CONCLUSIONS: Radical surgery performed 14-21days apart after SEMS placement has been shown to improve minimally invasive rates and 5-year DFS rates. The addition of neoadjuvant radiotherapy and chemotherapy during the interval does not appear to improve long-term survival, although this conclusion is based on the results of only 15 patients.

Prostaglandin E1 administration post liver transplantation and renal outcomes: A retrospective single center experience.

Prostaglandin E1 (PGE1), or alprostadil, is a potent vasodilator that improves hepatic blood flow and reduces ischemia-reperfusion injury post-liver transplantation (LT). However, the benefits of PGE1 on renal function after LT have not yet been well described. To assess the impact of PGE1 administration on renal function in patients who underwent liver or liver-kidney transplant. This retrospective study included all patients who underwent liver or liver-kidney transplant at our institution from January, 2011 to December, 2021. Patients were classified based on whether they received PGE1. PGE1 was administered post-LT to those with transaminases > 1000 U/L in the immediate postoperative period. Demographics, post-LT treatments and/or complications, renal function, and survival were analyzed. Multivariable logistic regression analysis was performed, and a two-tailed P value < 0.05 was considered statistically significant. A total of 145 patients underwent LT, with 44 (30%) receiving PGE1. Baseline patient characteristics were comparable, except the PGE1 group had significantly higher aspartate aminotransferase (AST) (1961.9 U/L ± 1862.3 U/L vs 878 U/L ± 741.4 U/L, P = 0.000), alanine aminotransferase (1070.6 U/L ± 895 U/L vs 547.7 U/L ± 410 U/L, P = 0.000), international normalized ratio on post-LT day 1 (2 ± 0.74 vs 1.8 ± 0.4, P = 0.03), a longer intensive care unit stay (8.1 days ± 11.8 days vs 3.8 days ± 4.6 days, P = 0.003), more vasopressor use (55.53 hours ± 111 hours vs 16.33 hours ± 26.3 hours, P = 0.002), and higher immediate postoperative complications (18.6% vs 4.9%, P = 0.04). The PGE1 group also had a significantly higher 90-day readmission rate (29.6% vs 13.1%, P = 0.02) and lower 1-year liver graft survival (87.5% vs 98.9%, P = 0.005). However, 30-day readmission (31.6% vs 27.4%, P = 0.64), LT complications (hepatic artery thrombosis, biliary complications, rejection of liver graft, cardiomyopathy), 1-year patient survival (96.9% vs 97.8%, P = 0.77), overall liver graft survival, and overall patient survival were similar between the two groups (95.4% vs 93.9%, P = 0.74 and 88.4% vs 86.9%, P = 0.81 respectively). Although the PGE1 group had a significantly lower glomerular filtration rate (eGFR) on post-LT day 7 (46.3 mL/minute ± 26.7 mL/minute vs 62.5 mL/minute ± 34 mL/minute, P = 0.009), the eventual need for renal replacement therapy (13.6% vs 5.9%, P = 0.09), the number of dialysis sessions (0.91 vs 0.27, P = 0.13), and eGFR at 1-month (37.2 mL/minute ± 35.9 mL/minute vs 42 mL/minute ± 36.9 mL/minute, P = 0.49), 6-months (54.8 mL/minute ± 21.6 mL/minute vs 62 mL/minute ± 21.4 mL/minute, P = 0.09), and 12-months (63.7 mL/minute ± 20.7 mL/minute vs 62.8 mL/minute ± 20.3 mL/minute, P = 0.85) post-LT were similar to those in the non-PGE1 group. In patients who received PGE1 for ischemia-reperfusion injury, despite immediate acute renal injury post-LT, the renal function at 1-month, 6-months, and 12-months post-LT was similar compared to those without ischemia-reperfusion injury. Prospective clinical trials are needed to further elucidate the benefits of PGE1 use in renal function.

Development and Validation of a Competitive Risk Model in Elderly Patients with Transitional Cell Bladder Carcinoma.

BACKGROUND Transitional cell bladder carcinoma (tcBC) is the predominant form of bladder cancer, making up around 95% of reported cases. Prognostic factors for older individuals with tcBC differ from those affecting younger patients. The main purpose of this study was to establish a prognostic competing risk model for elderly patients with tcBC. MATERIAL AND METHODS We conducted a retrospective analysis using data from the SEER database, randomly assigning patients to training and validation groups. We applied proportional subdistribution hazard (SH) to assess risk factors for cancer-related mortality (CSM). A competitive risk model was created to predict cancer-specific survival in elderly patients with tcBC. Model validation involved evaluating the area under the receiver operating curve, the consistency index, and a calibration curve. The Kaplan-Meier (K-M) curve was then used to compare mortality risk between high-risk and low-risk groups identified by the model. RESULTS This study randomly assigned 61 293 patients from the SEER database into training (42 905 patients) and validation (18 388 patients) groups in a 7: 3 ratio. Using a proportional subdistribution hazards model, we identified prognostic risk factors such as age, race, sex, marital status, TNM staging, grade, and metastatic status in brain, bone, liver, and lung. We developed a competitive risk model to predict 5-year cancer-specific survival (CSS) in elderly tcBC patients, achieving consistency index (C-index) values of 0.814 and 0.815 for the training and validation groups, respectively. Kaplan-Meier (K-M) analysis revealed 5-year survival probabilities of 35.1% (high-risk) and 42.2% (low-risk) in the training group, with similar rates of 35.7% and 42.0% in the validation group, both showing statistically significant differences (log-rank P<0.01). CONCLUSIONS We successfully established a competitive risk model for forecasting cancer-specific survival in elderly tcBC patients, primarily relying on these identified risk factors. The validation outcomes indicate the model's accuracy and dependability, making it a highly efficient predictive instrument. This tool enables making personalized clinical decisions for both medical professionals and patients.

Prediction of prognosis, efficacy of lung adenocarcinoma by machine learning model based on immune and metabolic related genes

BackgroundThe aim of this study is to integrate immune and metabolism-related genes in order to construct a predictive model for predicting the prognosis and treatment response of LUAD(lung adenocarcinoma) patients, aiming to address the challenges posed by this highly lethal and heterogeneous disease.Material and methodsUsing TCGA-LUAD as the training subset, differential gene expression analysis, batch survival analysis, Lasso regression analysis, univariate and multivariate Cox regression analysis were performed to construct prognostic related gene models. GEO queue as validation subsets, is used to validate build Riskscore. Then, we explore the Riskscore and mutation status, immune cell infiltration, the relationship between immune therapy and chemotherapy, and build the model of the nomogram.ResultsThe Riskscore has been determined to be composed of seven gene. In the high-risk group defined by this score, both early-stage and advanced-stage LUAD patients exhibit a decreased overall survival rate. The mutation status of patients as well as immune cell infiltration show associations with the Riskscore value obtained from these genes’ expression levels. Furthermore, there exist variations in response to immunotherapy as well as sensitivity to commonly used chemotherapy drugs among different individuals. Lastly, when using a column line plot model based on the calculated Riskscore values, we obtain a concordance index (C-index) was 0 .716 (95% CI 0.671–0.762), and time-dependent ROC predicted probabilities of 1-, 3- and 5-year survival for LUAD patients were 0.752, 0.725 and 0.654, respectively.ConclusionIn conclusion, we have successfully developed a predictive model incorporating immune and metabolism-related genes, encompassing gene expression levels of CAT/CCL20/GPI/INSL4 NT5E/GSTA3/GNPNAT1. This comprehensive model not only enables the prognosis prediction for LUAD patients but also facilitates the prediction of their response to first-line chemotherapy drugs and immune checkpoint inhibitors, thus demonstrating its broad potential in clinical applications. However, our study still has limitations as it is based on TCGA and GEO databases with limited pathological characteristics of patients. Therefore, more practical and valuable factors are needed to predict efficacy. The crosstalk between metabolism and immunity remains to be explored. Finally, this study lacks experimental evidence for the underlying gene expression of prognosis and further research is required.