Search Results (4,911)

Background/Objectives: The prognostic significance of young age in breast cancer (BC) remains controversial, with varying findings across studies. This study aimed to evaluate the imaging characteristics, pathological features, and survival outcomes of BC in young patients aged ≤ 35 years by dividing them into two groups and to compare outcomes between these subgroups to determine whether very young age alone is associated with worse prognosis. Methods: This retrospective study included patients aged ≤ 35 years with malignant breast lesions who underwent image-guided interventions at a single center between January 2011 and December 2024. Patients were divided into two groups: Group 1 (≤30 years) and Group 2 (31–35 years). Demographic, imaging, and pathological data, as well as survival outcomes, were analyzed. Results: A total of 34 patients (Group 1: n = 14, Group 2: n = 20) with malignant breast lesions underwent 40 image-guided procedures. No significant differences were observed between groups in imaging features, pathological characteristics, or pTNM stage distribution. Median follow-up was 68 months. One-year overall survival (OS) was 100% in both cohorts; 5-year OS rates were 100% and 92.3%, respectively, with no statistically significant difference (p = 0.784). Median event-free survival (EFS) was 60.5 months, also without a significant difference between groups (p = 0.897). None of the clinicopathological factors assessed were significantly associated with OS in this exploratory analysis. Conclusions: In women ≤ 35 years, tumor characteristics and patient outcomes were similar between those aged ≤ 30 and 31–35 years. OS and EFS were favorable in both groups, indicating that within the ≤35-year population studied, being ≤30 years old was not associated with worse outcomes than being 31–35 years old. Although advanced stage disease was more frequently observed in the younger group, this difference was not statistically significant. Full article

Background: Second-line treatment selection in relapsed extensive-stage small-cell lung cancer (ES-SCLC) is commonly guided by the platinum-free interval, but the optimal approach for patients progressing 3–6 months after first-line platinum-based therapy remains uncertain. We compared platinum-containing doublet chemotherapy with single-agent chemotherapy in this clinically ambiguous subgroup. Methods: This multicenter retrospective real-world cohort study included patients with ES-SCLC or recurrent metastatic SCLC after prior limited-stage disease who received first-line platinum-based chemotherapy, achieved disease control, and progressed within a platinum-free interval of 90–180 days. Treatment allocation was at the discretion of the treating physician and was not randomized. The primary endpoint was progression-free survival (PFS); secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Because of the non-randomized design, the treatment effect was examined across multiple analytic approaches, including multivariable Cox regression, propensity score adjustment, and stabilized inverse probability of treatment weighting (IPTW). Results: Of 105 patients, 54 received single-agent chemotherapy and 51 received platinum-containing doublet therapy; 39 (37.1%) had received first-line atezolizumab. Baseline characteristics were imbalanced in favor of the doublet group, which had a longer platinum-free interval, fewer pleural metastases, and a higher rate of objective response to first-line therapy. ORR was higher with doublet therapy (31.4% vs. 11.1%, p = 0.016), as was DCR (62.7% vs. 33.3%, p = 0.003). Median PFS was 4.4 months (95% CI 3.4–5.8) with doublet therapy versus 3.1 months (95% CI 2.7–3.7) with single-agent chemotherapy (unadjusted HR 0.53, 95% CI 0.36–0.80; p = 0.002). Median OS was 6.5 months (95% CI 5.4–8.0) versus 5.4 months (95% CI 4.1–6.0), a difference that was not statistically significant (HR 0.68, 95% CI 0.46–1.01; p = 0.054). The PFS estimate favored doublet therapy in all sensitivity analyses but was attenuated with increasingly complete adjustment for treatment selection (multivariable HR 0.46, 95% CI 0.29–0.72; propensity-adjusted HR 0.58, 95% CI 0.38–0.88; IPTW HR 0.68, 95% CI 0.38–1.20, p = 0.184). No OS estimate reached statistical significance in any model. Grade ≥ 3 adverse events were similar between groups (66.7% vs. 64.8%, p = 0.842). Conclusions: In this non-randomized cohort of patients relapsing within a 90–180-day platinum-free interval, platinum-containing doublet chemotherapy was associated with higher response rates and longer PFS, without an increase in severe toxicity, but no overall survival benefit was demonstrated. Because baseline prognostic factors consistently favored the doublet group and the PFS advantage was attenuated after propensity-based adjustment, these findings should be regarded as hypothesis-generating. They are nonetheless consistent with randomized data showing improved PFS but not OS with platinum rechallenge, and support platinum-containing rechallenge as a reasonable option in carefully selected patients rather than as a demonstrated survival-prolonging strategy. Full article

Background and Objectives: The relative prognostic information provided by different nodal metrics and the independent role of primary tumor size remain unclear in gastric cancer. This study evaluated the association of metastatic lymph node count and primary tumor size with disease-free survival (DFS) in stage II–III gastric cancer (GC) treated with a surgery-first approach. Materials and Methods: This retrospective single-center study included 128 patients who underwent curative-intent gastrectomy between 2003 and 2019 without neoadjuvant treatment. A multivariable Cox model with clinically prespecified covariates was fitted. Metastatic lymph node count, pathological N (pN) category, lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) were each added separately to the same base clinical model and compared using the Akaike information criterion (AIC). Results: During a median follow-up of 114.3 months, 86 DFS events occurred. Each additional metastatic lymph node was independently associated with a higher hazard of a DFS event (HR, 1.049; 95% CI, 1.022–1.076; p < 0.001), and this association persisted across four sensitivity analyses. Primary tumor size was not independently associated with DFS. All four nodal metrics improved model fit, with LNR yielding the lowest AIC. Conclusions: Metastatic lymph node count was independently and robustly associated with DFS, whereas primary tumor size was not. Although LNR provided the best relative model fit, these within-cohort comparisons do not establish clinical superiority, and external validation is required. Full article

Background: Radiotracer- and magnetic seed-based targeted axillary staging techniques are increasingly used after neoadjuvant chemotherapy (NAC) in patients with initially node-positive breast cancer who convert to clinical node-negative (ycN0) status. However, these technologies remain unavailable in many centres worldwide. We evaluated the effectiveness of radiotracer-free axillary staging using dual-tracer sentinel lymph node biopsy (SLNB) with indocyanine green (ICG) and methylene blue, with particular focus on the clinical implications of clipped node non-retrieval. Methods: This retrospective single-centre cohort study included 49 patients with biopsy-proven cN1 breast cancer who achieved ycN0 status following NAC and underwent dual-tracer SLNB using ICG and methylene blue between 2021 and 2024. Clipped node retrieval rates, tracer-specific detection patterns, recurrence outcomes, and disease-free survival (DFS) were analysed. Clinical outcomes, including recurrence and disease-free survival, were compared between patients with successful and unsuccessful clipped node retrieval. Results: Clipped node retrieval was achieved in 41 of 49 patients (83.7%). ICG outperformed methylene blue for clipped node identification (80.5% vs. 61.0%) and was the sole detecting tracer in 39.0% of cases. Using methylene blue alone would have reduced the retrieval rate to 51.0% (p = 0.001). ICG identified the clipped node in all six patients with axillary micrometastases (ypN1mi). Clipped node non-retrieval occurred in eight patients, all of whom had negative SLNB findings and did not undergo completion axillary lymph node dissection. Recurrence rates were similar between the retrieval and non-retrieval groups (17.1% vs. 12.5%, p = 1.000), and no isolated axillary recurrences were observed. Baseline tumour size was the only independent predictor of disease-free survival in multivariable analysis (HR 2.05, 95% CI 1.20–3.51; p = 0.008). Conclusions: Radiotracer-free axillary staging using ICG and methylene blue achieved a high clipped node retrieval rate in patients with ycN0 breast cancer after neoadjuvant chemotherapy. ICG significantly improved clipped node identification compared with methylene blue alone and identified the clipped node in all patients with residual nodal micrometastatic disease. Among patients with negative SLNB findings, clipped node non-retrieval was not associated with higher recurrence rates or worse disease-free survival during follow-up. However, given the small number of clipped node non-retrieval cases (n = 8) and recurrence events (n = 8), these findings should be interpreted with caution and require confirmation in larger prospective studies. These findings support the feasibility of a radiotracer-free dual-tracer approach in settings where radiotracer-based techniques are not available. Prospective multicentre studies are warranted to validate both the oncological performance of radiotracer-free axillary staging and the clinical implications of clipped node non-retrieval. Full article

Background: Prostate cancer patients with intermediate disease risk [Gleason score (GS)7] can be divided into two groups: GS = 7(3 + 4) (ISUP 2) (favorable disease risk) and GS = 7(4 + 3) (ISUP 3) (unfavorable disease risk). Low-dose-rate brachytherapy (LDR-BT) is an effective treatment for low- and intermediate-disease-risk patients. Objectives: The main goal of this study was to evaluate the effectiveness of LDR-BT monotherapy in prostate cancer patients classified as ISUP 3 when compared with ISUP 2 patients. Methods: This was a retrospective study that evaluated prostate cancer patients classified as ISUP 2 and ISUP 3 followed up at the Center for the Treatment of Urological Diseases, Portugal, who underwent LDR-BT. Overall survival (OS), biochemical recurrence-free survival (BRFS), bone metastasis and complications post-LDR-BT treatment were evaluated. Results: A total of 602 patients classified with GS = 7 (481/602 ISUP 2 and 121/602 ISUP 3) treated with LDR-BT were recruited. High OS rates and a reduced frequency of complications were described in both groups of patients. ISUP 3 patients had a lower BRFS rate, a higher risk of biochemical recurrence, and developed more bone metastasis in a shorter period when compared with ISUP 2 patients. No significant differences were detected in prostate-cancer-specific mortality between groups. Conclusions: LDR-BT monotherapy is a safe and effective treatment for prostate cancer patients with favorable and unfavorable intermediate disease risk, with similar OS rates and reduced complications. Full article

Background/Objectives: Diet is increasingly recognized as a modifiable factor in cancer survivorship; however, the impact of post-diagnostic dietary habits on breast cancer (BC) outcomes remains uncertain. This systematic review aimed to evaluate the association between diet after BC diagnosis and clinical outcomes and to provide an updated synthesis of the evidence, with particular emphasis on dietary assessment methods, methodological heterogeneity, and evidence gaps. Methods: We systematically reviewed randomized controlled trials (RCTs) and prospective cohort studies that investigated post-diagnostic dietary exposures among women with BC. Outcomes of interest included all-cause mortality (ACM), breast cancer-specific mortality (CSM), recurrence (R), overall survival (OS), and disease-free survival (DFS). Sources of methodological heterogeneity were assessed, and findings were synthesized using a structured narrative approach. Results: A total of 39 studies were included (8 RCTs and 31 prospective cohort studies), comprising over 90,000 participants. Evidence from RCTs, including low-fat and multi-component interventions, showed largely null or inconsistent effects on BC-specific outcomes. Findings from cohort studies were heterogeneous. Associations for individual nutrients and food groups were generally inconsistent across studies, whereas healthier dietary patterns and higher diet quality scores were associated with reduced ACM. Associations with BC-specific outcomes were less consistent. Overall, the available evidence was characterized by substantial methodological heterogeneity, overlapping study populations, and low-to-moderate certainty. Conclusions: Current evidence suggests that post-diagnostic dietary habits may contribute more to overall survivorship than to BC-specific prognosis. Methodological heterogeneity, particularly in dietary assessment, should be taken into account when interpreting findings. The principal contribution of this review is the identification of important methodological limitations and evidence gaps that currently limit confidence in the available literature. Future research should employ more accurate dietary assessment methods and comprehensive nutritional evaluation to clarify the role of nutrition in BC outcomes. Full article

Background: Substantial inter-individual variability in imatinib systemic exposure may influence both efficacy and toxicity. Based on recommendations of the International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT), the IRCCS-CRO of Aviano started in 2018 offering physicians the opportunity to monitor plasma concentrations of imatinib and its active metabolite, norimatinib, as part of a diagnostic service for patients with Gastrointestinal Stromal Tumor (GIST). This study aims to evaluate the potential clinical utility of imatinib Therapeutic Drug Monitoring (TDM) in predicting response and toxicity in a real-world cohort of 63 patients with GIST. Methods: Imatinib and its active metabolite norimatinib trough concentrations (C_min) were quantified using a validated LC–MS/MS method. Associations between drug exposure and clinical–demographic characteristics, treatment-related toxicity, and progression-free survival (PFS) were evaluated. Results: A total of 437 plasma samples from 63 patients were collected. Marked inter- and intra-patient variability in imatinib exposure was observed (43% and 31% respectively); 67% of patients receiving 400 mg/day had a C_min below the recommended target concentration (1100 ng/mL). Female sex was significantly associated with higher imatinib exposure (median C_min 1114 vs. 786 ng/mL in males; p = 0.0018). Combined age–sex analysis showed a significant difference between women and men < 60 years (1041 vs. 668 ng/mL; p = 0.0068, Bonferroni-adjusted). A strong exposure–toxicity relationship emerged, with higher imatinib levels in samples collected at toxicity occurrence vs. the others (1728 vs. 927 ng/mL; p < 0.0001), without a direct association between sex and toxicity. No significant association between C_min and PFS was observed; however, disease progression was more frequent in patients with C_min < 500 ng/mL and absent in those with C_min >1500 ng/mL (60% vs. 0%, respectively). Conclusions: TDM was found to be a potentially useful tool for predicting clinically relevant toxicity and outcome. Sex and age significantly influence exposure, supporting tailored dosing strategies. Full article

Background: Active surveillance (AS) represents a cornerstone of personalized medicine in uro-oncology, offering an individualized management strategy for low- and selected favourable intermediate-risk prostate cancer that aligns treatment intensity with patient-specific risk profiles; however, real-world adherence data from southern European academic centres remain scarce. This study aimed to evaluate AS discontinuation rates, reasons for transition to active treatment, and quality of life (QoL) in a single-centre Greek university hospital cohort. Methods: This is an observational retropective cohort study of patients enrolled in an AS protocol at the First Department of Urology, Aristotle University of Thessaloniki, between October 2016 and July 2022. Treatment-free survival (TFS) was estimated using Kaplan–Meier analysis. Associations between AS discontinuation and age at diagnosis, PSA level, and Charlson Comorbidity Index (CCI) were explored using univariable and multivariable Cox proportional hazards regression. QoL, erectile function, and anxiety were assessed cross-sectionally in patients remaining on AS using SF-12, IIEF-6, STAI-6, and MAX-PC. Results: Thirty-six patients were included (32 low-risk; 4 favourable intermediate-risk), with a median age of 69.5 years, median PSA of 6.92 ng/mL, and median CCI of 3. After a median follow-up of 24 months (IQR 21–45), 19 patients (52.8%) transitioned to active treatment; the median time to treatment was 21 months (IQR 17–34). Among the 10 patients with a known reason for discontinuation, 6 (31.6% of all discontinued) showed histopathological or clinical disease progression, 3 (15.8%) had a PSA increase alone, and 1 (5.3%) transitioned due to urinary symptoms; the reason was unknown in 9 cases (47.4%). In exploratory Cox regression, PSA ≥ 7.0 ng/mL was the only factor with complete documented output significantly associated with transition to active treatment (univariable HR 3.70, 95% CI 1.35–10.1, p = 0.011; multivariable HR 3.93, 95% CI 1.42–10.9, p = 0.008). Cross-sectional QoL assessment in 10 patients remaining on AS demonstrated median scores above established population norms for SF-12 and below clinical anxiety thresholds on STAI-6 and MAX-PC. Conclusions: In this single-centre cohort, AS discontinuation occurred early and at a rate higher than that of established international programmes, consistent with the institution’s initial AS experience. Higher PSA at diagnosis was the only factor with complete analytical documentation to be significantly associated with earlier transition. Full article

Background: Squamous cell carcinomas (SCCs) share squamous differentiation and may engage the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) pathway, although their causes, biology, and treatment differ by anatomical site. We evaluated tumor response, short-term survival, and grade 3–4 adverse events after neoadjuvant immune-checkpoint blockade, with or without chemotherapy, followed by surgery. Methods: A comprehensive search of PubMed, Embase, the Cochrane Library, and clinical trial registries was conducted from inception to October 2024. Prospective and retrospective studies evaluating neoadjuvant immunotherapy, with or without chemotherapy, before surgery in patients with SCC were included. In mixed-histology studies, data were eligible only when SCC outcomes could be extracted separately. Pooled proportions and 95% confidence intervals (CIs) were estimated with random-effects models. Results: A total of 44 studies involving 2586 patients with six anatomical SCC groups were included. The pooled objective response rate (ORR) was 0.70 (95% CI, 0.59–0.80), clinical complete response (cCR) rate was 0.17 (95% CI, 0.10–0.28), and pathological complete response (pCR) rate was 0.30 (95% CI, 0.27–0.34). The pooled 1-year progression-free survival (PFS), disease-free survival (DFS), and overall survival (OS) rates were 0.82 (95% CI, 0.79–0.86), 0.86 (95% CI, 0.75–0.92), and 0.92 (95% CI, 0.90–0.93), respectively. The pooled incidence of grade 3–4 adverse events was 0.18 (95% CI, 0.14–0.23). Because the PD-L1 subgroup contained only one study for most outcomes, checkpoint-target subgroup findings were considered exploratory. Conclusions: Existing predominantly single-arm evidence suggests antitumor activity of neoadjuvant immune-checkpoint blockade, with or without chemotherapy, in selected patients with resectable SCC. Because esophageal SCC accounted for most studies and clinical heterogeneity was substantial, these pooled proportions should not be interpreted as comparative effects or as evidence of uniform benefit across SCC sites. Full article

Background/Objectives: The aim of this study was to determine the oncologic outcomes for adult patients with primary extremity soft tissue sarcoma (ESTS) treated at the sarcoma referral center in the Republic of Slovenia. Methods: Patients from a prospectively maintained institutional database treated between January 2009 and December 2023 were retrospectively analyzed. The cohort was stratified into a high-risk group (HRG) and a low-risk group (LRG). Survival analyses focused on the HRG. Multivariable Cox models were constructed for local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS), and predictors of major wound complications were evaluated using multivariable logistic regression. Results: Among 315 included patients, 242 (76.8%) were in the HRG. In this group the median age was 61.5 years, 82.6% of tumors were in the lower extremity, and median tumor size was 9.0 cm. The most common histological subtype was undifferentiated pleomorphic sarcoma (28.5%). Clear margins were achieved in 86.8%, major postoperative complications occurred in 19.0%, and 60.7% of patients underwent radiotherapy. Local recurrence developed in 11.2%, regional recurrence in 5.0%, and distant metastasis in 32.6%. The corresponding 5-year overall survival, disease-specific survival, LRFS, and DMFS were 69.8%, 73.7%, 87.9%, and 66.8% in the HRG, respectively. In the LRG, only one local recurrence occurred and the 5-year LRFS was 100.0%. Preoperative radiotherapy showed a borderline association with major wound complications in the HRG (OR 2.70, 95% CI 1.00–7.28, p = 0.050). Tumor grade and size remained independent predictors of distant metastases, whereas margin status was not significantly associated with LRFS or DMFS. The primary amputation rate in the whole series was 2.9%. Conclusions: Treatment of primary ESTS patients in a specialized national referral cancer center achieved good overall survival (69.8%), a high limb-salvage rate (97.1%), and good local control, affirming that routine primary amputation is rarely needed. Outcomes in high-risk histologies remained driven mainly by distant metastases and showed clear histology-specific differences, whereas low-risk histologies had excellent outcomes with surgery alone. Preoperative radiotherapy was associated with a higher risk of major wound complications. Full article

Background: The treatment paradigm for relapsed/refractory (R/R) large B-cell lymphoma (LBCL) has undergone significant change with the advent of CD19-directed chimeric antigen receptor T-cell (CAR-T) therapies and CD20 × CD3 bispecific antibodies (BsAbs). Although both approaches have shown high response rates in single-arm studies, the absence of prospective randomized head-to-head comparisons has resulted in true clinical equipoise. Methods: A narrative synthesis was conducted, incorporating pivotal and updated phase 2 and 3 trial data, real-world evidence, and published meta-analyses. Results: In the second-line setting, CAR-T therapy demonstrates superior event-free survival, progression-free survival, and overall survival compared to standard-of-care chemo-transplant regimens. In the third-line setting, a pooled meta-analysis indicates significantly higher complete response rates for CAR-T compared with BsAbs, as well as superior 12-month progression-free survival. BsAbs provide immediate availability, greater accessibility, more favorable neurotoxicity profiles, and are feasible for frail or elderly patients. Real-world data show that BsAb complete response rates are consistently lower than those observed in clinical trials, whereas CAR-T real-world effectiveness closely aligns with pivotal trial outcomes. Emerging phase 3 data on fixed-duration and monotherapy bispecific regimens suggest that a genuine, if less mature, curative fraction may also be achievable among BsAb-treated complete responders. Conclusions: CAR-T therapy remains the standard of care for fit, eligible patients with R/R LBCL in second- and third-line settings with curative intent, providing superior depth and durability of response and a growing potential for long-term cure. BsAbs constitute a critical therapeutic alternative for patients ineligible for CAR-T, those with rapidly progressive disease, frail or elderly individuals, and as bridging strategies. A patient-centered, scenario-specific clinical decision framework is recommended. Full article

Background: The role of primary tumor resection (PTR) in patients with de novo stage IV colorectal cancer remains controversial, particularly in the context of patient selection and tumor biology. This study aimed to evaluate the association between PTR and survival outcomes and to identify clinical, molecular, and inflammatory-nutritional prognostic factors in patients with de novo stage IV colorectal cancer. Methods: Medical records of 204 patients with de novo stage IV colorectal adenocarcinoma treated at Ankara Etlik City Hospital from December 2022 to December 2025 were reviewed retrospectively. Patients were grouped according to PTR status. Baseline clinicopathological features, molecular tumor profile, metastatic disease extent, treatment characteristics, and inflammatory-nutritional markers were recorded. Survival outcomes were assessed in terms of progression-free survival (PFS) and overall survival (OS) using the Kaplan–Meier method and Cox proportional hazards regression models, as well as 1:1 propensity score matching and sensitivity analyses. Results: PTR was performed in 114 patients (55.9%), while 90 patients (44.1%) did not undergo PTR. Patients who underwent PTR were younger, had better Eastern Cooperative Oncology Group (ECOG) performance status, and more frequently had single-organ metastatic disease. In the unmatched cohort, patients who underwent PTR had longer median PFS and OS than those without PTR (15.88 vs. 11.03 months and 16.14 vs. 11.54 months, respectively; both log-rank p < 0.001). In the adjusted Cox models, PTR corresponded to lower risks of progression (hazard ratio [HR]: 0.50; 95% confidence interval [CI]: 0.34–0.74; p < 0.001) and death (HR: 0.48; 95% CI: 0.30–0.77; p = 0.002), whereas BRAF mutation showed higher risks of progression (HR: 3.00; 95% CI: 1.70–5.29; p < 0.001) and death (HR: 3.42; 95% CI: 1.83–6.38; p < 0.001). In the propensity score–matched cohort comprising 50 matched pairs, PTR remained associated with a lower risk of progression or death (HR: 0.59; 95% CI: 0.40–0.87; p = 0.007), whereas its association with OS was not statistically significant (HR: 0.69; 95% CI: 0.42–1.13; p = 0.141). Sensitivity analyses generally yielded estimates favoring PTR, although the statistical significance of the association with OS varied across analyses. Patients with higher prognostic nutritional index (PNI) values showed more favorable survival outcomes. Conclusions: In this retrospective cohort, PTR was consistently associated with longer PFS, whereas its association with OS was less robust across the adjusted analyses. Because these patients had a more favorable baseline profile, these associations should be viewed with caution and in relation to patient selection. BRAF mutation and PNI emerged as important prognostic factors, supporting a multidimensional approach to survival assessment that incorporates metastatic disease burden, tumor biology, and inflammatory-nutritional status. Full article

Background and Objectives: Relapsed/refractory non-Hodgkin lymphoma (R/R NHL) remains a major therapeutic challenge, particularly in patients with peripheral T-cell lymphomas (PTCL), who frequently exhibit poor responses to salvage therapy and inferior survival outcomes. Achieving adequate disease control before autologous stem cell transplantation (ASCT) is a critical determinant of long-term survival. The bendamustine, gemcitabine, vinorelbine, and prednisolone (BEGEV) regimen has demonstrated high efficacy and favorable tolerability in relapsed/refractory classical Hodgkin lymphoma; however, data regarding its role in NHL are extremely limited. Materials and Methods: We conducted a retrospective, single-center analysis of patients with R/R NHL who received the BEGEV regimen as salvage therapy. Clinical characteristics, response rates, transplantation outcomes, progression-free survival (PFS), overall survival (OS), and safety data were evaluated. Treatment responses were assessed according to standard radiologic response criteria. Survival analyses were performed using the Kaplan–Meier method. Results: A total of 68 patients with R/R NHL were included in the analysis. Diffuse large B-cell lymphoma (DLBCL) was the predominant histological subtype, accounting for 49 patients (72.1%). BEGEV was administered predominantly in later salvage settings. Response assessments were available for 56 patients. Among evaluable patients, the objective response rate (ORR) was 73.2%, whereas the ITT ORR was 60.3% (41/68). Following BEGEV therapy, 25 patients (36.8%) proceeded to autologous stem cell transplantation (ASCT), while 8 patients (11.8%) underwent allogeneic stem cell transplantation (allo-SCT). Exploratory analyses demonstrated longer overall survival (log-rank p = 0.012) and progression-free survival (log-rank p = 0.011) among patients who subsequently underwent transplantation; however, these findings should be interpreted with caution because of the retrospective study design and the potential for selection and immortal time biases. Median PFS and OS were 4 and 26 months, respectively. Adverse events were predominantly hematologic and generally manageable. Conclusions: BEGEV may represent a reasonable salvage regimen for selected patients with R/R NHL and may facilitate disease control allowing subsequent transplantation in selected patients, including selected PTCL patients. Full article

Background: Cardiovascular disease (CVD) prevention in ageing populations requires simple and clinically accessible markers that may help identify individuals at elevated risk. Tooth loss is a common oral condition in middle-aged and older adults and may reflect cumulative inflammatory burden, impaired oral function, and broader health vulnerability. However, longitudinal evidence from nationally representative populations across different countries remains limited. We investigated whether a baseline of missing teeth was independently associated with incident CVD in three nationally representative ageing cohorts from China, the United States, and England. Methods: We analyzed data from the China Health and Retirement Longitudinal Study (CHARLS), the Health and Retirement Study (HRS), and the English Longitudinal Study of Ageing (ELSA). Participants aged 45 years or older without baseline CVD and with available baseline tooth status were included. Missing teeth were assessed at baseline as a dichotomous exposure. Incident CVD was defined as newly reported heart disease and/or stroke during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with sequential adjustment for sociodemographic, lifestyle, and clinical covariates. Kaplan–Meier, subgroup, and sensitivity analyses were also performed. Results: A total of 31,805 participants were included, comprising 13,451 from CHARLS, 11,384 from HRS, and 6970 from ELSA. During follow-up, 2336 incident CVD events occurred in CHARLS, 2914 in HRS, and 545 in ELSA. In fully adjusted models, missing teeth was associated with a higher risk of incident CVD in all three cohorts, with HRs of 1.31 (95% CI, 1.14–1.50) in CHARLS, 1.43 (95% CI, 1.29–1.57) in HRS, and 1.86 (95% CI, 1.49–2.31) in ELSA. Kaplan–Meier analyses showed consistently lower CVD-free survival among participants with missing teeth, and the associations remained broadly robust across subgroup and sensitivity analyses. Conclusions: In three nationally representative cohorts from China, the United States, and England, a baseline of missing teeth was independently associated with a higher risk of incident CVD among middle-aged and older adults. These findings suggest that missing teeth may serve as a simple and clinically accessible marker of elevated cardiovascular risk and support greater integration of oral health into cardiovascular risk assessment and preventive strategies for ageing populations. Full article

This study evaluated the potential of synergistically degraded low-molecular-weight chitosan (LMW-CS) as a functional feed additive to promote growth, antioxidant capacity, innate immunity, and disease resistance in Pacific white shrimp (Litopenaeus vannamei). High-molecular-weight chitosan (HMW-CS, approximately 85 kDa) was degraded using γ-irradiation in combination with H₂O₂ to produce LMW-CS with improved functional properties. Shrimp were fed five experimental diets for 4 weeks: a control diet, HMW-CS0.4 (0.4% w/w), LMW-CS0.1 (0.1% w/w), LMW-CS0.2 (0.2% w/w), and LMW-CS0.4 (0.4% w/w). Growth performance, oxidative stress markers, antioxidant enzyme activities, lysozyme activity, immune-related gene expression, bacterial load, and survival after Vibrio parahaemolyticus challenge were evaluated. The results indicate that dietary LMW-CS supplementation improved growth performance and feed utilization, with LMW-CS0.2 showing significantly higher final weight, total weight gain, and average daily gain than the control group (p < 0.05). Antioxidant assays showed that LMW-CS reduced malondialdehyde levels and increased reduced glutathione, nitric oxide, glutathione reductase, catalase, superoxide dismutase, glutathione peroxidase, and glutathione-S-transferase activities in both plasma and hepatopancreas (p < 0.05). Lysozyme activity was significantly enhanced, particularly in the LMW-CS0.4 and HMW-CS0.4 groups (p < 0.05). Gene expression analysis revealed upregulation of genes associated with growth regulation, antimicrobial defense, pathogen recognition, and prophenoloxidase activation, including igf2, cstn, lgbp, lyz, and propo2. Gut microbiota profiling showed that chitosan supplementation altered bacterial community composition, reduced the relative abundance of some Vibrio-associated taxa, and descriptively lowered predicted pathogenic and stress-tolerant bacterial phenotypes. Following the Vibrio parahaemolyticus challenge, shrimp fed LMW-CS0.4 showed the lowest bacterial load and highest survival rate, indicating improved disease resistance (p < 0.05). Overall, synergistically degraded LMW-CS enhanced growth, redox balance, innate immune competence, gut microbial structure, and resistance to V. parahaemolyticus, supporting its potential as an antibiotic-free functional feed additive for sustainable shrimp aquaculture. Full article