Survival Advantage Research Articles

Early versus late nephrology referral and patient outcomes in chronic kidney disease: an updated systematic review and meta-analysis

BackgroundNephrology referral has been recognized as a modifiable factor influencing patient outcomes. The study aimed to compare clinical outcomes among patients referred early versus late to nephrologists.MethodsWe searched online database from inception to June 1, 2022, to obtain all eligible literature reporting outcomes of patients referred early versus late to nephrologists. The early and late referral was defined by the time at which patients were referred to nephrologists before dialysis onset.ResultsSeventy-two studies with over 630,000 patients met the inclusion criteria. A lower likelihood of all-cause mortality (HR = 0.67, 95% CI: 0.62–0.72) was achieved among patients referred early to nephrologists. The survival advantage of early referral was apparent in the first 6 months and extended to the 5th year after dialysis onset (6 months: HR = 0.52, 95% CI: 0.40–0.68; 5 years: HR = 0.67, 95% CI: 0.60–0.74). The early referral was associated with shorter durations of initial hospitalization, a higher rate of kidney transplantation (RR = 1.41, 95% CI: 1.12–1.78), a lower likelihood of emergency start (RR = 0.39, 95% CI: 0.28–0.54), a higher likelihood of permanent access creation (RR = 3.34, 95% CI: 2.43–4.59), increased initial use of permanent access (RR = 2.60, 95% CI: 2.18–3.11), and reduced initial catheter use (RR = 0.43, 95% CI: 0.32–0.58).ConclusionsOur study showed a lower risk of mortality, shorter lengths of initial hospitalization, and better preparations for renal replacement therapy among patients referred early to nephrologists. Early nephrology care should be promoted to improve the management of advanced chronic kidney disease.

Loss of correlated proteasomal subunit expression selectively promotes the 20SHigh state which underlies luminal breast tumorigenicity

Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity. As seen in luminal BrCa cell lines, this imbalance limits the number of double-capped 19S-20S-19S holocomplexes (30S) formed and promotes free 20S catalytic core accumulation that is widely-believed to confer survival advantage to tumors. By retaining connectivity with key tumor 19S:20S interface nodes, the PSMD9 19S subunit chaperone emerges as a crucial regulator of 26S/30S:20S ratios sustaining tumor cell proteasome function. Disrupting this connectivity by depleting PSMD9 in MCF7 cells introduces structural anomalies in the proteasome, and shifts dependence from 20SHigh to a deregulated 26SHigh state invoking anti-tumor responses which opens up clinically-relevant therapeutic possibilities.

GNA15 induces drug resistance in B cell acute lymphoblastic leukemia by promoting fatty acid oxidation via activation of the AMPK pathway.

The prognosis of B cell acute lymphoblastic leukemia (B-ALL) is poor, primarily due to drug resistance and relapse. Ga15, encoded by GNA15, belongs to the G protein family, with G protein-coupled receptors playing a crucial role in multiple biological process. GNA15 has been reported to be involved in various malignancies; however, its potential role in B-ALL remain unknown. In this study, high expression of GNA15 in B-ALL was observed in multiple databases. We further confirmed an increased transcriptional level of GNA15 in newly diagnosed B-ALL patients which was closely correlated with relapse. We showed that GNA15 promoted cell growth, inhibited apoptosis and enhanced drug resistance in leukemia cell lines. Metabolomics analysis revealed a significant enrichment of fatty acid oxidation (FAO) according to the GNA15 expression. We further confirmed that GNA15 could enhance FAO process as evidenced by the upregulation of key molecules involved in FAO including carnitine palmitoyl transferase1 (CPT1), CPT2 and CD36. And inhibition of FAO using etomoxir partially reversed the drug resistance caused by high expression of GNA15. Mechanism study showed that GNA15 promoted FAO by up-regulation of AMPK phosphorylation thus leading to survival advantage in leukemia cells. In conclusion, we observed elevated GNA15 transcript levels in B-ALL, which were associated with relapse. GNA15 could induce drug resistance though activation of the AMPK/FAO axis in leukemia cell lines. Targeting GNA15 and FAO may represent potential therapeutic strategy for improving the prognosis of B-ALL.

Autologous Nonmyeloablative Hematopoietic Stem Cell Transplantation for Diffuse Cutaneous Systemic Sclerosis: Identifying Disease Risk Factors for Toxicity and Long-Term Outcomes in a Prospective, Single-Arm Trial.

Two randomized trials for patients with diffuse systemic sclerosis (SSc) demonstrated an overall survival (OS) and event-free survival (EFS) advantage of autologous hematopoietic stem cell transplantation (AHSCT) using CD34+ selected peripheral blood stem cells (PBSCs) compared with monthly cyclophosphamide (CY). We asked if an unmodified PBSC graft followed by maintenance mycophenolate mofetil (MMF) after AHSCT, instead of a CD34+ selected graft, could provide comparable AHSCT outcomes. Twenty patients with high-risk SSc were enrolled in a prospective, single-arm trial with CY 200 mg/kg and horse antithymocyte globulin (ATG; CY200/ATG), followed by unmanipulated autologous PBSC, and then MMF maintenance starting at 2 months after AHSCT. Point estimates of OS and EFS at 5 years after AHSCT were 85% (95% confidence interval [CI] 60.4%-94.9%) and 75% (95% CI 50%-88.7%), respectively. Median follow-up was 7.5 years (range 5.6-11.6) after transplant for living patients. Eight patients (40%) required intensive care unit treatment early after transplant. Early transplant-related mortality occurred in two patients (10%). Five patients developed relapse/progression of SSc after AHSCT. Four of nine patients with anti-RNA polymerase III antibodies had prior scleroderma renal crisis and the lowest quartile of estimated glomerular filtration rate (eGFR) on study entry; all four patients developed prolonged organ failure/death early after transplant. We observed favorable OS and EFS after AHSCT for patients with SSc, using CY200/ATG, unmanipulated PBSCs, and MMF posttransplant maintenance, which was comparable to trials with CD34+ graft selection. We identified a possible risk factor, pretransplant low eGFR, for adverse outcomes after AHSCT.

225Aс-PSMA-617 therapy in metastatic castration-resistant prostate cancer

177Lu-PSMA-617 is a new therapy option for PSMA-positive metastatic castrate-resistant metastatic prostate cancer (mCRPC) with proven efficacy. 225Ac-PCMA-617 is an alpha emitter, making this drug potentially more powerful. Despite the active use of 225Ac-PSMA-617 worldwide, no randomized phase III studies have yet been conducted. The present prospective cohort study presents the experience of 225Ac-PSMA-617 use in the A.F. Tsyb MRRC. Material and Methods. the study included mCRPC patients with prostate-specific membrane antigen (PSMA) overexpression confirmed by PET-CT or SPECT-CT, who received the first course of therapy in 2023. Results. Forty three patients received 1 to 6 (median 2) administrations of 225Ac-PSMA-617, 26 (60 %) of these patients had a history of 177Lu-PSMA-617 therapy, 13 (30 %) had a history of radium chloride [223Ra] therapy, and 10 (23 %) patients had no history of chemotherapy. Five (12 %) had liver metastases at the time of inclusion in the study. PSA reduction of more than 50 % was recorded in 55 % of patients, with biochemical response significantly more frequent in the PSMA-naïve group, 63 % vs 35 %; the number of adverse events was also lower in this group. But no advantage in overall survival (OS) in PSMA-naïve patients was revealed at the present time. Favorable prognosis factors included a history of radium chloride [223Ra] therapy; in contrast, liver metastasis was a negative prognostic factor. the study found no differences in OS among taxane-naïve patients and patients with a history of 1–2 lines of chemotherapy. Continued therapy with androgen receptor targeted agents after initiation of 225Ac-PSMA-617 treatment also showed no effect on OS. Conclusions. 225Ac-PCMA-617 may be effective in 177Lu-PCMa resistance, but there are no data on the increase in overall patient survival when 225Ac-PCMA-617 is administered as first-line radioligand therapy.

Sex Differences in Melanoma Survival-a GEM study.

Sex differences in melanoma are prominent, with females having a significant survival advantage. However, it is unclear why we see this survival advantage. Here we investigate the relationship between sex, clinicopathologic variables, and melanoma specific survival in 1,753 single primary melanomas from patients in the GEM study. Using Cox proportional hazard models and formal mediation analysis, the effect of sex on survival is explained largely by differences in the clinicopathologic features of tumors at diagnosis. Specifically, we find evidence that 86.5% of the effect of sex on melanoma survival is mediated by differences in age at diagnosis, Breslow thickness, ulceration, mitoses and site (HR 1.85, P < .001). This analysis indicates that the female survival advantage in melanoma is not due primarily to a direct effect of sex (HR 1.19, P = .42) but is largely a result of an indirect effect of sex mediated by clinicopathologic features.

Experience of using chemotherapy treatment for the first recurrence of ovarian cancer

Background. The main goal of treating patients with recurrent ovarian cancer is to prolong life and improve its quality. Approaches to the treatment of recurrent ovarian cancer have changed over the past decade. The choice of antitumor drug therapy is determined by the duration of platinum-free interval and the use of targeted therapy with bevacizumab or olaparib. Treatment regimens for relapses are not unified and treatment outcomes are contradictory. Aim: to analyze treatment outcomes of different chemotherapy regimens in patients with the first recurrence of ovarian cancer, depending on the duration of platinum-free interval. Material and Methods. A retrospective analysis of the first recurrence of ovarian cancer in 446 patients treated at the Primorsky Regional Oncology Center in the period 2004–2021 was carried out. All patients were divided into two groups depending on the treatment option for relapse: repeated cytoreduction followed by chemotherapy or only second-line chemotherapy, and into four groups depending on the chemotherapy regimens: 1 – platinum and taxane agents; 2 – platinum and taxane agents with bevacizumab; 3 – platinum agents and non-taxane agents with bevacizumab; 4 – monotherapy with non-platinum agents with bevacizumab. Results. Significant advantages in progression-free survival after second-line chemotherapy (PFS-2) were observed in patients with platinum-resistant relapse after the 4th chemotherapy regimen. Patients with platinum-sensitive relapse had the best treatment outcomes after the 3rd chemotherapy regimen and repeated cytoreduction followed by chemotherapy with a platinum-free interval of 6–12 months and 12–24 months with any platinum-containing chemotherapy regimen. In the platinum-free interval of more than 24 months, significant benefits were observed with a combination of platinum and taxane agents + bevacizumab. In the group of patients without surgery, there were significant benefits in all three intervals when prescribing a combination of platinum and non-oxane agents ± bevacizumab. There was a tendency to increase PFS-2 in patients with low-grade serous ovarian carcinoma compared with patients with high-grade serous carcinoma. The best rates of relapse-free survival were noted with maintenance therapy with olaparib. Conclusion. In patients with localized recurrence of ovarian cancer and a platinum-free interval of more than 6 months, it is advisable to perform repeated cytoreduction followed by chemotherapy, taking into account the duration of the platinum-free interval. The administration of PARP inhibitors in the maintenance therapy of platinum-sensitive recurrence of ovarian cancer improves treatment results.

Convergent Isobilateral Leaves Increase the Risk for Mangroves Facing Human-Induced Rapid Environmental Changes.

Understanding plant adaptations in extreme environments is crucial, as these adaptations often confer advantages for survival. However, a significant gap exists regarding the genetic mechanisms underlying these adaptations and their responses to human-induced rapid environmental change (HIREC). This study addresses the question of whether genetic convergence occurs among plants with similar adaptive features, specifically focusing on isobilateral leaves in mangrove species. Here, we analyse the genetic convergence of isobilateral leaves in mangroves that have independently adapted to coastal intertidal zones. Our findings reveal that genetic convergence is evident in gene families involved in leaf abaxial and adaxial development, with strong selection pressures identified in photosynthesis and leaf polarity pathways. Despite these adaptations, mangrove species with isobilateral leaves occupy narrower ecological niches and face diminishing suitable habitat areas projected under various HIREC scenarios. These results indicate that while convergent traits enhance local adaptation, they may also increase vulnerability to ongoing environmental changes. This research provides valuable insight into the interplay between genetic adaptation and environmental resilience, underscoring the necessity for targeted biodiversity conservation strategies that safeguard specific adaptive traits amid rapid environmental shifts.

Comparison of mitral valve repair versus replacement for mitral valve regurgitation.

Mitral regurgitation (MR) is a prevalent valvular abnormality categorized as primary or secondary based on aetiology. Surgical intervention, particularly mitral valve repair, is often preferred over replacement due to its association with better outcomes. However, the benefits of repair versus replacement, especially in secondary MR, remain debated. This study aims to evaluate the long-term survival and reoperation rates in patients undergoing mitral valve repair compared to mitral valve replacement for MR in a cardiothoracic surgery unit in North-West England and in subgroups with degenerative and secondary aetiology. We analysed 1 724 consecutive patients undergoing first-time mitral valve surgery (repair: n=1 243; replacement: n=481) between 2000-2021. Primary outcome was all-cause mortality. Genetic matching and overlap weighting were used to balance baseline characteristics. Median follow-up was 7.1 years. In the matched cohort, mitral valve replacement was associated with higher rates of blood transfusion (29%vs 22%), longer ICU stays, and more strokes (3.7%vs 0.4%). While 90-day mortality did not differ significantly between groups, long-term follow-up showed a survival advantage for repair (HR: 1.32, 95% CI: 1.08-1.63). Although repair had higher reoperation rates (4.3%vs 2.1%), the composite of death or reoperation did not differ significantly. In degenerative MR subgroup, repair showed superior long-term survival, whereas in secondary MR, no significant survival difference was observed between strategies. Among patients suitable for either surgical strategy, mitral valve repair showed better long-term survival compared to replacement, particularly in degenerative MR. However, this advantage was not observed in secondary MR.

Treatment Quality of Rectal Cancer Patients in Certified Colorectal Cancer Centers Versus Non-Certified Hospitals: A Comparative Analysis.

Background/Objectives: The certification of hospitals as colorectal cancer centers aims to improve treatment quality, but evidence supporting its effectiveness remains limited. This study evaluated the impact of certification on treatment outcomes for rectal cancer patients in Germany. Methods: We conducted a retrospective analysis of 14,905 patients with primary rectal cancer (UICC Stages I-III) treated at 271 hospitals. Treatment outcomes were compared between certified colorectal cancer centers (3624 patients in 55 hospitals) and non-certified hospitals (11,281 patients in 216 hospitals). Additionally, a subset analysis examined outcomes before and after certification within the same institutions. Results: Certified centers demonstrated higher utilization of preoperative imaging (endorectal ultrasound: 70.7% vs. 58.2%, p < 0.001; pelvic MRI: 39.1% vs. 28.5%, p < 0.001) and lower rates of intraoperative complications (4.6% vs. 6.2%, p < 0.001). Surgical quality indicators, including M.E.R.C.U.R.Y. classification (Grade 1: 86.5% both groups, p = 0.620) and anastomotic leakage rates (11.3% vs. 11.9%, p = 0.407), were comparable between certified and non-certified hospitals. Despite treating patients with more favorable tumor stages, certified centers showed no significant advantage in 5-year overall survival (82.8% vs. 82.0%, p = 0.880) or 30-day mortality (2.6% both groups, p = 0.869). Hospital stays were marginally shorter in certified centers (19.46 vs. 20.24 days, p < 0.001). Conclusions: While certification was associated with improved adherence to diagnostic protocols and reduced intraoperative complications, it did not significantly impact surgical quality or long-term survival outcomes. These findings suggest that certification alone may not guarantee superior treatment quality, as hospitals participating in quality assurance programs achieved comparable results without formal certification.

Twenty-Year Survival Analysis of Adeno-Associated Virus Vector Serotype 2-Mediated Gene Therapy to the Central Nervous System for CLN2 Disease.

CLN2 disease (late infantile neuronal ceroid lipofuscinosis) is an autosomal recessive, neurodegenerative lysosomal storage disease that results from loss of function mutations in the CLN2 gene, which encodes tripeptidyl peptidase 1. It affects the central nervous system (CNS) with progressive neurodegeneration and early death, typically at ages from 8 to 12 years. Twenty years ago, our phase I clinical trial treated subjects with CLN2 disease by a catheter-based CNS administration of an adeno-associated virus vector serotype 2 (AAV2) expressing the CLN2 gene. Here we present an analysis of the survival of the 10 treated children and find 2 distinct survival groups with a wide disparity in survival. Group 1 (n = 7) had the typical mean survival of 8.8 ± 0.5 years of age, 3.8 ± 0.6 years post-therapy. Group 2 (n = 3) had a markedly longer mean survival of 23.4 ± 2.4 years of age and 14.9 ± 2.8 years post-therapy (p < 0.00002, survival of group 1 vs. group 2). Long survivors (group 2) at the time of treatment were older (group 1: 5.0 ± 0.6 years; group 2: 8.5 ± 0.9 years; p < 0.02); had similar disease severity (Hamburg clinical score group 1: 4.7 ± 0.5, group 2: 3 ± 0.0, p > 0.05); and had larger CNS ventricular volume (81.1 ± 22.2 cm3 vs. 27.3 ± 7.2 cm3 for group 1; p < 0.02). While the genotype of 3, group 2 subjects, had one allele (509-1G>C) identical to that of three in group 1, the second allele was different. This was unlikely to explain the survival difference, as alleles for both groups were equally predicted deleterious by the Combined Annotation-Dependent Depletion score: 34.9 ± 0.7 and 32.8 ± 0.3 for groups 1 and 2, respectively (a score of >20 is considered deleterious). This represents one of the longest survival studies (up to 20 years) of AAV-treated individuals with hereditary disorders and demonstrates variability of therapeutic efficacy where the genotype on its own has no apparent survival advantage. Protocol registration numbers for the original study: NCT00151216 and NCT00151268; www.clinicaltrials.gov.

Different surgical methods for FIGO stage IVB cervical cancer patients receiving chemotherapy: a population-based study.

To assess survival differences between non-extensive surgery (NES) and extensive surgery (ES) in International Federation of Gynecology and Obstetrics (FIGO) stage IVB cervical cancer patients receiving chemotherapy from a population-based database, the Surveillance, Epidemiology and End Results. Propensity matching was conducted to minimize heterogeneity. Survival analysis was performed by the Kaplan-Meier method, log-rank test, and Cox proportional hazards model. A total of 154 patients met screening criteria, among whom 84 patients (84/154) underwent NES while 70 patients (70/154) underwent ES. After matching, no survival advantage was observed in ES group compared with NES group (p=0.066; hazard ratio [HR]=1.54; 95% confidence interval [CI]=0.97-2.42). Stratified analyses suggested ES prolonged overall survival in patients with histology other than squamous cell carcinoma and adenocarcinoma (p=0.028; HR=0.36; 95% CI=0.15-0.89) and American Joint Committee on Cancer (AJCC) T stage T1 (p=0.009; HR=0.18; 95% CI=0.05-0.66). Despite no survival benefit after regional lymph node surgery (p=0.629; HR=0.88; 95% CI=0.53-1.47), subgroup analyses demonstrated that patients younger than 50 (p=0.006; HR=0.21; 95% CI=0.07-0.64), with AJCC T stage T1 (p=0.002; HR=0.09; 95% CI=0.02-0.42), T3 (p=0.001; HR=0.02; 95% CI=0.00-0.21), hematogenous metastasis (p=0.036; HR=0.27; 95% CI=0.08-0.92) and without surgery of other sites (p=0.040; HR=0.01; 95% CI=0.00-0.79) might achieve longer survival after regional lymph node surgery. In conclusion, ES or regional lymph node surgery may provide survival advantage for certain subgroup of FIGO IVB cervical cancer patients receiving chemotherapy. However, it deserves large scale prospective clinical trials to confirm.

LP-118 is a novel B-cell lymphoma 2 / extra-large inhibitor that demonstrates efficacy in models of venetoclaxresistant chronic lymphocytic leukemia.

Patients with chronic lymphocytic leukemia (CLL) respond well to initial treatment with the B-cell lymphoma 2 (BCL2) inhibitor venetoclax. Upon relapse, they often retain sensitivity to BCL2 targeting, but durability of response remains a concern. We hypothesize that targeting both BCL2 and B-cell lymphoma-extra large (BCLXL) will be a successful strategy to treat CLL, including for patients who relapse on venetoclax. To test this hypothesis, we conducted a pre-clinical investigation of LP-118, a highly potent inhibitor of BCL2 with moderate BCLXL inhibition to minimize platelet toxicity. This study demonstrated that LP-118 induces efficient BAK activation, cytochrome C release, and apoptosis in both venetoclax-naïve and -resistant CLL cells. Significantly, LP-118 is effective in cell lines expressing the BCL2 G101V mutation and in cells expressing BCLXL but lacking BCL2 dependence. Using an immunocompetent mouse model, Eμ-TCL1, LP-118 demonstrates low platelet toxicity, which hampered earlier BCLXL inhibitors. Finally, LP-118 in the RS4;11 and OSU-CLL xenograft models results in decreases in tumor burden and survival advantage, respectively. These results provide a mechanistic rationale for the evaluation of LP-118 for the treatment of venetoclax-responsive and -relapsed CLL.

Short and Long-Term Outcomes of Lung Transplantation from Brain Death vs. Circulatory Death Donors: A Meta-analysis of Comparative Studies.

To investigate through a meta-analysis of comparative studies the impact of donor type (brain death DBD vs circulatory death DCD) on the short- and long-term outcomes of lung transplantation(LTx). Literature search (terms "lung transplantation" AND "donation after circulatory death") was performed up to July 2022 and studies comparing outcomes of LTx from DCD versus DBD were selected. Primary endpoints were early and long-term mortality. Secondary outcomes included primary graft dysfunction (PGD),acute rejection and postoperative complications. The long-term survival was analyzed by retrieving data from each available Kaplan-Meier and restricted mean survival time difference between DBD and DCD for long-term survival was estimated. 21 studies were included comprising 60105 patients (DBD=58548 DCD=1557). Recipient and donor baseline characteristics were similar between the two groups. No significant publication bias was observed. The estimated pooled odds ratio of early mortality favored DBD (OR=0.75,CI=0.56-1.00,I2=0%). No statistically significant difference was observed in the risk of acute rejection (OR=1.33,CI=0.82-2.17), and PGD grade 2-3 (OR=0.88,CI=0.69-1.13). One- and 5-year survival were 82.1% and 51.2%, and 86.2% and 62.7% for DBD and DCD groups, respectively (Log-rank,p<0.0001). Unadjusted hazard ratio was 0.693, with DCD as reference. DCD lungs demonstrated improved survival by 4.82% over 5-years when compared to DBD lungs. This meta-analysis of comparative studies between DCD and DBD demonstrates significant long-term survival advantage of DCD LTx despite an initial small but statistically significant increased mortality risk in the short-term. Data supports the continued implementation of DCD to increase the lung donor pool.

Bilateral Mediastinal Lymphadenectomy Is Associated With Potential Survival Advantages in Patients With Stage I Non-Small Cell Lung Cancer Who Undergo Lung Resection.

The optimal lymphadenectomy approach for solid-dominant stage I non-small cell lung cancer (NSCLC) is controversial. We compared postlobectomy survival outcomes to elucidate. Patients diagnosed with solid-dominant stage I NSCLC between 2008 and 2015 were included and grouped according to the mode of lymphadenectomy. Disease-free survival (DFS) and overall survival (OS) were compared, and survival analysis was performed among the groups. Cox analysis was used to identify independent prognostic factors. Nomograms for survival prediction on the basis of the lymphadenectomy mode were constructed and internally calibrated. Propensity score matching (PSM) was used to account for potential confounders. Subgroup comparisons between bilateral mediastinal lymphadenectomy (BML), systematic nodal dissection (SND), lobe-specific nodal dissection (L-SND), and selected nodal sampling (SNS) were conducted. In total, 983 patients were included. The 5-year OS rates were 98.2%, 86.9%, 86.4%, and 82.8% (P = .006), and the 5-year DFS rates were 87.1%, 76.4%, 69.5%, and 70.9% (P = .008) in the BML, SND, L-SND, and SNS groups, respectively. Given PSM, patients who underwent BML had longer OS (hazard ratio [HR], 0.358 [95% CI, 0.127 to 1.008]; P = .052) and DFS (HR, 0.563 [95% CI, 0.295 to 1.074]; P = .081) than patients who underwent SND with marginal significance. Compared with L-SND and SNS, BML was associated with significantly improved OS (HR, 0.343 [95% CI, 0.123 to 0.958]; P = .041 and HR, 0.250 [95% CI, 0.088 to 0.709]; P = .009, respectively) and DFS (HR, 0.474 [95% CI, 0.258 to 0.868]; P = .016 and HR, 0.467 [95% CI, 0.232 to 0.938]; P = .032, respectively). Subgroup analyses demonstrated that in male patients and those whose tumors were larger or more advanced, BML was associated with significantly better OS and DFS than other types of lymphadenectomies. BML may be associated with improved survival in patients with solid-dominant stage I NSCLC, and BML is recommended for such patients, especially those with large tumors or more advanced disease.

Survival rates in comprehensive conservative care compared to dialysis therapy in elderly end-stage kidney disease patients: a propensity score analysis

Initiating dialysis therapy in elderly patients with end-stage kidney disease (ESKD) is a challenging decision. We aimed to examine the mortality rates among elderly patients who underwent hemodialysis, peritoneal dialysis, or comprehensive conservative care. This retrospective cohort study included elderly patients (≥70 years) with ESKD who selected their treatment options from January 2008 to December 2018. Patients were categorized into three groups: hemodialysis, peritoneal dialysis, and comprehensive conservative care. The outcome of interest was all-cause mortality analyzed using flexible parametric survival models. Propensity score analysis with inverse probability treatment weighting technique was performed, incorporating age, Charlson Comorbidity Index score, and estimated glomerular filtration rate. The study included 719 elderly ESKD patients with mean age of 78.2 ± 4.9 years, 52.3% were male, and 60.1% died during the median follow-up period of 22.1 months. In a fully adjusted model, patients receiving comprehensive conservative care (n = 50) had higher mortality rates than those receiving hemodialysis (n = 317) (adjusted hazard ratio [HR] 5.60; 95% CI 2.26–13.84, p < 0.001). However, patients who received peritoneal dialysis (n = 352) had a similar mortality rate when compared to those who received hemodialysis (adjusted HR 1.38; 95% CI 0.78–2.44, p = 0.275). The higher mortality rate in the comprehensive conservative care group remained significantly higher than in the hemodialysis group among patients aged ≥80 years (adjusted HR 4.97; 95% CI 1.32–18.80, p = 0.018). Among elderly patients (≥70 years), treatment with dialysis was associated with longer survival rates. This survival advantage persisted in patients aged ≥80 years who chose hemodialysis or peritoneal dialysis over comprehensive conservative care.

Influence of Organ-Specific Extranodal Involvement on Survival Outcomes in Stage IV Diffuse Large B-Cell Lymphoma.

The prognostic significance of extranodal sites in stage IV diffuse large B-cell lymphoma (DLBCL) remains uncertain, making it challenging to select appropriate treatment strategies for individual patients. In this study, we aimed to evaluate the influence of different extranodal sites on prognosis in young patients with stage IV DLBCL who achieved complete remission (CR) following initial chemo-immunotherapy and to explore the potential of autologous hematopoietic stem cell transplantation (ASCT) as a consolidation treatment for specific patient subgroups. We retrospectively reviewed data from 119 patients with DLBCL aged < 60 years who achieved CR after chemo-immunotherapy between 2008 and 2020. Patient survival rates were analyzed in correlation with different extranodal sites using univariate and multivariate models. Additionally, we assessed the effect of ASCT on 5-year progression-free survival (PFS) and overall survival (OS) in patients with different extranodal sites involved. A retrospective bicenter study. Univariate analysis revealed a significant decrease in survival rates in patients with a Deauville score of 3 and those with extranodal DLBCL affecting the spleen, bone marrow, nasosinus, and liver. In multivariate analysis, only nasosinusal involvement remained a significant predictor of reduced OS. Patients with spleen involvement benefited significantly from ASCT in terms of 5-year PFS and OS, whereas those with nasosinusal involvement did not demonstrate any survival advantage with ASCT. Our findings highlight the influence of specific extranodal sites on the prognosis of patients with stage IV DLBCL. The data indicate a clear need for precise patient stratification based on extranodal involvement for more effective treatment planning. Notably, patients with spleen involvement appear to benefit from ASCT, suggesting that this strategy could be useful in this subgroup. Further prospective studies are needed to confirm and incorporate these findings into clinical practice.

Regorafenib Treatment for Recurrent Glioblastoma Beyond Bevacizumab-Based Therapy: A Large, Multicenter, Real-Life Study

Background/Objectives: In the REGOMA trial, regorafenib demonstrated an overall survival advantage over lomustine, and it has become a recommended treatment for recurrent glioblastoma in guidelines. This study aimed to evaluate the effectiveness and safety of regorafenib as a third-line treatment for patients with recurrent glioblastoma who progressed while taking bevacizumab-based therapy. Methods: This retrospective, multicenter study in Turkey included 65 patients treated between 2021 and 2023 across 19 oncology centers. The main inclusion criteria were histologically confirmed isocitrate dehydrogenase (IDH)-wildtype glioblastoma, progression after second-line bevacizumab-based treatment, and an Eastern Cooperative Oncology Group (ECOG) performance status score of ≤2. Patients received regorafenib 160 mg once daily for the first 3 weeks of each 4-week cycle. Results: The median age of the patients was 53 years (18–67 years), with a median progression-free survival of 2.5 months (95% Confidence Interval: 2.23–2.75) and a median overall survival of 4.1 months (95% CI: 3.52–4.68). The median overall survival was improved in patients who received subsequent therapy after regorafenib treatment compared with those who did not (p = 0.022). Progression-free survival was longer in patients with ECOG 0–1 than in those with ECOG 2 (p = 0.042). The safety profile was consistent with that of the REGOMA trial, with no drug-related deaths observed. Conclusions: Regorafenib shows good efficacy and safety as a third-line treatment for recurrent glioblastoma after bevacizumab-based therapy. This study supports the use of regorafenib and emphasizes the need for further randomized studies to validate its role and optimize treatment strategies.

Improving outcomes for very preterm babies in England: does place of birth matter? Findings from OPTI-PREM, a national cohort study

ObjectiveBabies born between 27+0 and 31+6 weeks of gestation contribute substantially towards infant mortality and morbidity. In England, their care is delivered in maternity services colocated with highly specialised neonatal...

Establishment and Characterization of Bisexually Fertile Triploid Dwarf Surf Clam Mulinia lateralis.

Triploids are widely used to rapidly achieve genetic improvements of organisms due to their fast growth and enhanced environmental adaptability. Artificially induced triploids are generally considered to be infertile owing to the obvious inhibition of gonadal development. Recently, some fertile individuals with reduced advantages have been found in triploid bivalves, which is a notable deviation from the original intention of artificially inducing triploids. This study utilized dwarf surf clams (Mulinia lateralis), a promising model organism of bivalves, to develop a model for exploring the potential mechanism of triploid reproduction. The results showed that the optimal induction condition for triploid M. lateralis, determined by orthogonal experiments, was 0.5mg/L cytochalasin B (CB) to inhibit PB2 for 20min, resulting in a triploidy rate of 95.57% and a hatching rate of 60.25%. By tracking the development of M. lateralis, we found that the induced triploids could develop normally to maturity and exhibited significant growth and survival advantages post-metamorphosis. Although the triploidy rate exhibited a slight decline overtime, it remained high, with a ratio of 90.63% at 120 dpf. Histological observation confirmed that the gonadal development pattern of triploid M. laterali was similar to that of diploids, but it also showed characteristics such as developmental retardation, few mature gametes, and gamete gigantism. The dynamic expression of genes related to gonadal development provided further molecular evidence for this phenomenon. Additionally, 82.6% of triploid M. laterali exhibited normal spawning behavior, produced fewer but larger viable gametes, and could generate offspring with full developmental potential. Flow cytometry analysis revealed that sperm of triploid M. laterali was aneuploid, with a DNA content of about 1.5 times that of diploid sperm, and the ploidy levels of mating offspring were 2N (DD, diploid female × diploid male), 2.5N (DT, diploid female × triploid male), 2.5N (TD, triploid female × diploid male), and 3N (TT, triploid female × triploid male), respectively. Overall, the artificially induced triploid M. laterali has been confirmed to be bisexually fertile, which will provide a unique model for exploring the underlying mechanisms of advantageous trait formation and fertility regulation in triploids, and offer a valuable platform for the study of ploidy control and polyploidization in bivalves. Please check and confirm that the authors and their respective affiliations have been correctly identified and amend if necessary. Yes, i have checked and it is OK.