Search Results (4,903)

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%. Conclusion: 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

Background: The prognostic significance of extranodal disease in classical Hodgkin lymphoma remains incompletely defined. Although contemporary models such as the Advanced Hodgkin International Prognostic Index (A-HIPI) improve systemic risk stratification, it remains unclear whether outcomes are more closely associated with specific extranodal organ involvement or with the overall burden of extranodal dissemination. Methods: This retrospective single-center study included 89 patients with predominantly advanced-stage classical Hodgkin lymphoma, including a minority of high-risk stage II bulky cases, and documented extranodal involvement at diagnosis. Extranodal disease was evaluated according to both organ-specific involvement and extranodal organ burden (EOB), defined as single extranodal organ involvement (single EO) versus involvement of two or more extranodal organs (≥2 EO). Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan–Meier analysis and Cox proportional hazard models. Risk stratification was examined using both the International Prognostic Score (IPS) and A-HIPI. Results: Patients with ≥2 EO had significantly inferior OS compared with those with single EO involvement (5-year OS, 66.8% vs. 96.7%; log-rank p = 0.018), whereas the difference in PFS did not reach statistical significance (5-year PFS, 49.6% vs. 73.5%; log-rank p = 0.108). A-HIPI-based stratification significantly discriminated OS (5-year OS, 92.2% vs. 78.2%; p = 0.001) and showed borderline discrimination for PFS (5-year PFS, 71.5% vs. 57.2%; p = 0.053). In the combined analysis, patients with high A-HIPI risk and ≥2 EO had the poorest outcomes, with a 5-year PFS of 34.1% and a 5-year OS of 25.0%. In a parsimonious multivariable Cox model including EOB and A-HIPI-predicted 5-year risk as a continuous variable, ≥2 EO remained associated with inferior OS (HR 3.83, 95% CI 1.34–10.97; p = 0.013), while its association with PFS was adverse but not statistically significant (HR 1.83, 95% CI 0.86–3.88; p = 0.114). Organ-specific extranodal involvement showed limited and inconsistent associations with survival across A-HIPI- and IPS-defined subgroups. Conclusions: In this retrospective single-center cohort, involvement of multiple extranodal organs was associated with inferior OS after adjustment for continuous A-HIPI-predicted risk, whereas its association with PFS did not reach statistical significance. Individual extranodal sites showed no consistent prognostic associations. These exploratory and hypothesis-generating findings suggest that quantitative assessment of extranodal organ burden may complement existing clinical risk measures; however, confirmation in larger, contemporary, externally validated cohorts is required before clinical application. Full article

Background: Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men. In real-world clinical practice, non-random treatment allocation may result in confounding by indication, as patients with a greater disease burden are more likely to receive chemotherapy. We evaluated the association between treatment strategy and recurrence-free survival using propensity score–based inverse probability of treatment weighting (IPTW). Methods: We retrospectively analyzed 114 patients who underwent radical orchiectomy for TGCT between 2015 and 2024. Patients were classified into active surveillance and chemotherapy groups. Stabilized IPTW was used to balance baseline clinicopathological characteristics. Recurrence-free survival was evaluated using Kaplan–Meier analysis and Cox proportional hazards regression. Residual post-weighting imbalance was addressed by additional covariate adjustment. Results: During follow-up, 29 of 114 patients (25.4%) experienced recurrence. Unadjusted Kaplan–Meier analysis demonstrated no statistically significant difference in recurrence-free survival between treatment groups (log-rank p = 0.150). Consistently, the unadjusted Cox proportional hazards model showed no statistically significant association between treatment strategy and recurrence-free survival (HR = 1.85, 95% CI 0.79–4.34; p = 0.158). After IPTW, treatment strategy remained not significantly associated with recurrence-free survival (HR = 0.96, 95% CI 0.43–2.13; p = 0.911). Additional adjustment for residual post-weighting imbalance yielded similar results (HR = 0.94, 95% CI 0.43–2.03; p = 0.876). Conclusions: After adjustment for measured baseline differences using IPTW, treatment strategy was not statistically significantly associated with recurrence-free survival. Given the limited number of recurrence events, wide confidence intervals, residual covariate imbalance, incomplete propensity-score overlap, and evidence of non-proportional hazards, these findings should be considered exploratory and should not be interpreted as evidence of equivalence. Full article

Background: Extramedullary disease (EMD) in multiple myeloma (MM) is associated with poor prognosis, yet the clinical distinctions between bone-related EMD (bEMD) and soft tissue-associated EMD (sEMD) remain incompletely characterized. This study aimed to compare the clinical features and outcomes of bEMD versus sEMD and to develop a simple pre-treatment risk stratification tool using baseline clinical parameters. Methods: We retrospectively analyzed 118 patients with MM and EMD treated at a single center from 2011 to 2025, including 72 bEMD and 46 sEMD cases. Baseline characteristics, laboratory parameters, cytogenetic abnormalities, and survival outcomes were compared. Results: Patients with sEMD had significantly higher serum β2-microglobulin (β2-MG) levels (6.4 mg/L vs. 4.5 mg/L, p = 0.007) and a higher proportion of relapsed/refractory disease (41.3% vs. 15.3%, p = 0.002) compared to bEMD. Median progression-free survival (PFS) and overall survival (OS) were markedly shorter in patients with sEMD than in those with bEMD (PFS: 12.0 vs. 29.0 months, p < 0.001; OS: 25.0 vs. 67.0 months, p = 0.009). Multivariate analysis identified thrombocytopenia (PLT < 100 × 109/L), elevated β2-MG, multisite extramedullary involvement, and TP53 deletion as independent adverse prognostic factors. A risk scoring system incorporating β2-MG (0–2 points), thrombocytopenia (1 point), and multisite involvement (1 point) stratified patients into low-risk (0–2 points) and high-risk (3–4 points) groups with significantly different PFS (27.0 vs. 10.0 months, p < 0.001) and OS (54.0 vs. 22.0 months, p = 0.008). Conclusions: sEMD represents a more aggressive subtype of MM with inferior outcomes. The proposed risk score, based on routinely available clinical parameters, effectively identifies high-risk patients at initial diagnosis and may guide individualized treatment strategies. Full article

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. Although the STRIDE regimen (durvalumab plus tremelimumab) has demonstrated an overall survival benefit in clinical trials, real-world evidence remains limited, particularly in Turkish clinical practice. This study aimed to evaluate the effectiveness and safety of first-line STRIDE therapy in patients with unresectable HCC treated in routine clinical practice. Methods: We conducted a retrospective multicenter study including patients with unresectable HCC who received first-line durvalumab plus tremelimumab through the Turkish national Early Access Program across 18 oncology centers. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan–Meier method, and exploratory Cox regression analyses were performed to evaluate baseline prognostic factors. Results: Thirty-two patients were included. The median PFS was 7.25 months (95% CI, 3.68–22.29), and the median OS was 11.43 months (95% CI, 4.50–not reached). The underlying liver disease etiology was non-viral in 53.1% of patients, hepatitis B virus in 40.6%, and hepatitis C virus in 6.3%. Grade ≥ 3 treatment-related adverse events occurred in fewer than 10% of patients. Conclusions: In this multicenter real-world cohort, first-line durvalumab plus tremelimumab appeared to be a feasible treatment option and was generally well tolerated in patients with unresectable HCC. However, given the retrospective design, small sample size, and absence of a control group, these findings should be interpreted cautiously and require confirmation in larger prospective comparative studies. Full article

Aquaculture production of Asian seabass is increasingly threatened by recurrent bacterial diseases, while practical vaccination strategies that provide protection against bacterial challenges involving multiple pathogens during extended grow-out periods remain limited. This study evaluated the immunological and protective effects of a sequential mucosal vaccination strategy in juvenile Asian seabass (Lates calcarifer; 200 fish per treatment, distributed among four replicate tanks of 50 fish) against four major bacterial pathogens: Flavobacterium covae, Vibrio harveyi, Vibrio vulnificus, and Photobacterium damselae. The vaccination regimen consisted of two nanoemulsion-based immersion vaccination events administered 14 days apart, followed by three oral chitosan–alginate hydrogel vaccination courses administered for 7, 5, and 3 consecutive days. Bacterial challenge experiments were conducted at three post-vaccination time points using immersion and intraperitoneal injection models. Growth performance and feed conversion were evaluated using replicate-tank means as the experimental units. Sequential vaccination did not significantly affect final body weight, weight gain, average daily gain, specific growth rate, or feed conversion ratio (p > 0.05). Vaccinated fish showed significantly higher antigen-specific IgM levels in skin mucus, intestinal mucus, and serum across the evaluated challenge conditions. Correspondingly, ighm, ighd, and ight expression was increased in the gills, skin, head kidney, and intestine, indicating enhanced immunoglobulin-associated responses in mucosal and lymphoid tissues. Full-length 16S rRNA gene sequencing showed vaccine-associated changes in gill and intestinal bacterial community composition, including a lower relative representation of several challenge-associated taxa and a higher relative representation of selected commensal-associated taxa. Vaccinated fish showed significantly higher cumulative survival following F. covae immersion, mixed V. harveyi/V. vulnificus/P. damselae immersion, and mixed-pathogen injection challenges (p < 0.05). These findings demonstrate that sequential nanoemulsion immersion priming and oral hydrogel boosting enhanced pathogen-specific humoral responses and increased immunoglobulin-gene expression. The sequential vaccination strategy improved survival following a separate Flavobacterium covae challenge and a combined Vibrio harveyi/Vibrio vulnificus/Photobacterium damselae challenge during the experimental period without adversely affecting growth. This needle-free strategy warrants further evaluation under commercial aquaculture conditions. Full article

Background: Aberrant DNA methylation is a hallmark of acute myeloid leukemia (AML) and contributes to leukemogenesis, treatment response, and clinical heterogeneity. While genome-wide methylation studies have identified prognostic methylation signatures, the impact of DNA methylation within pharmacologic pathways and AML-relevant disease genes remains incompletely understood. We investigated the association of DNA methylation in genes of pharmacokinetic/pharmacodynamic (PK/PD) pathways of drugs used to treat AML and in myeloid leukemia-related genes with treatment outcomes in pediatric AML. Methods: DNA methylation profiles from 924 pediatric AML patients treated on Children’s Oncology Group trials (AAML1031, AAML0531, and AAML03P1—available publicly) were analyzed as a discovery cohort. A validation cohort included 159 patients treated on the AML02 trial. A total of 2296 variable CpG sites mapping to 65 PK/PD genes and 107 AML biology/leukemia stemness genes were evaluated. Associations between CpG methylation, gene expression, event-free survival (EFS), overall survival (OS), and measurable residual disease after induction I (MRD1) were assessed using Cox proportional hazards, logistic regression, and correlation analyses. Results: Twenty-three CpG sites in PK/PD genes and forty-two CpG sites in AML-related genes were significantly associated with at least one clinical endpoint after Bonferroni correction (p < 2.17 × 10⁻⁵). Hypermethylation of drug transporters ABCA3, ABCC1, and SLC22A1, as well as pharmacologically relevant genes MPO, NOS3, and CTPS1, was associated with inferior survival and/or increased MRD1 positivity. Among AML biology genes, methylation of ETV6, NOTCH1, RUNX1, KIT, MPL, DNMT3A, and DNMT3B demonstrated consistent associations with outcomes across discovery and validation cohorts. Several genes exhibited significant inverse correlations between DNA methylation and gene expression, including MPO, KIT, MPL, SPINK2, and DNMT3B, supporting functional epigenetic regulation. Notably, hypermethylation of ABCA3, MPO, and MPL was reproducibly associated with poor OS and EFS in both cohorts. Conclusions: DNA methylation of key pharmacologic and leukemia-related genes is associated with clinical outcomes in pediatric AML. These findings identify biologically and clinically relevant epigenetic biomarkers that may improve risk stratification and support the development of precision medicine approaches incorporating DNA methylation profiling and epigenetic therapies in pediatric AML. Full article

Hepatocellular carcinoma (HCC) is an aggressive liver cancer requiring reliable biomarkers, while current approaches are limited by high-dimensional data and complex nonlinear gene interactions. In this study, differentially expressed genes were identified and fed to a deep autoencoder to reduce dimensionality, capture nonlinear interactions, and extract informative latent features. Predictive gene features were selected through mutual information (MI) ranking and LASSO regression and subsequently evaluated using logistic regression (LR), random forest (RF), and support vector machine (SVM) classifiers with 5-fold cross-validation (CV). The top 50 genes underwent enrichment analyses. Protein–protein interaction (PPI) networks were constructed to identify hub genes, followed by gene–drug interaction, transcription factor analysis, and survival validation. Enrichment analysis highlighted critical pathways involved in metabolic, signaling, and cell-cycle, and viral carcinogenesis. CV showed stable and high performance across classifiers (accuracy = 0.969, F1 ≈ 0.97), with RF and SVM achieving the highest AUC values (~0.983 and ~0.982). Independent tests showed excellent performance, with RF achieving perfect performance (1.0) across all evaluation metrics, confirming high feature discriminative power. Survival analysis showed that hub genes, including HSP90AB1, TUBA1B, PKM, H2AZ1, YWHAZ, ACLY, RAN, ILF2, KPNA2, and TXNRD1, were significantly associated with poor prognosis (HR > 1.5, p < 0.05), correlating with reduced overall, relapse-free, and disease-specific survival in HCC. The integrative novel framework effectively identifies biologically relevant biomarkers, providing insights into HCC mechanisms and potential targets for precision therapy. Full article

Background: Interim PET after two cycles (PET2) has historically guided risk-adapted therapy in Hodgkin lymphoma (HL). Its value with frontline brentuximab vedotin plus doxorubicin, vinblastine, and dacarbazine (BV + AVD) is uncertain, as BV + AVD improves progression-free survival and may reduce the prognostic relevance of early metabolic response. Our aim was to assess whether PET2 retains prognostic utility in HL patients treated with BV + AVD. Methods: We retrospectively reviewed 55 newly diagnosed classical HL patients treated with frontline BV + AVD. The primary endpoint was PET2 performance for predicting EOT PET positivity. Sensitivity, specificity, predictive values, and likelihood ratios were calculated with 95% confidence intervals. Results: Median age was 22 years (range 11–77), 49% were male, and 73% had stage III–IV disease. PET2 was negative in 51 patients (92.7%) and positive in 4 (7.3%). EOT PET was negative in 48 (87.3%) and positive in 7 (12.7%). Of seven EOT PET-positive patients, three were PET2-positive and four PET2-negative. Of 48 EOT PET-negative patients, 47 were PET2-negative and 1 PET2-positive. PET2 sensitivity was 42.9%, specificity 97.9%, positive predictive value 75.0%, and negative predictive value 92.2%. Positive likelihood ratio was 20.6; negative likelihood ratio was 0.58. Conclusions: In HL patients treated with BV + AVD, most achieve PET2 negativity, limiting interim PET discrimination. Negative PET2 adds little reassurance beyond the high baseline success rate, while positive PET2 is uncommon and identifies only a subset of eventual treatment failures. These findings question the routine use of PET2 to guide therapy in the BV + AVD era. Full article

Refractory celiac disease (RCeD) is a rare but severe complication of celiac disease characterized by persistent or recurrent malabsorptive symptoms and villous atrophy despite a strict gluten-free diet, after exclusion of ongoing gluten exposure, alternative enteropathies, and overt lymphoma. RCeD comprises two biologically distinct entities. RCeD-I is associated with phenotypically normal, polyclonal intraepithelial lymphocytes and generally reflects persistent gluten-independent mucosal inflammation with a relatively favorable prognosis. RCeD-II is defined by expansion of aberrant clonal intraepithelial lymphocytes lacking normal surface T-cell markers and is increasingly regarded as a low-grade intraepithelial lymphoma or in situ lymphomatous disorder, with substantial risk of progression to enteropathy-associated T-cell lymphoma (EATL). Mechanistic studies identify epithelial stress, IL-15-driven IEL survival, stromal and innate immune amplification, and cytotoxic epithelial injury as central drivers of refractory mucosal damage. In RCeD-II, aberrant IELs acquire a hybrid T/NK-like phenotype, persist through anti-apoptotic IL-15/JAK–STAT signaling, and induce enterocyte killing, while molecular alterations involving JAK1, STAT3, JAK/STAT regulators, NF-κB signaling, epigenetic regulators, and chromosomal abnormalities support stepwise lymphomagenesis. Recent single-cell multiomic studies further reveal genetically altered intestinal lymphocyte clones and intratumoral heterogeneity across the RCeD-II–EATL continuum. From a nutritional immunology perspective, RCeD illustrates a setting in which removal of the initiating dietary antigen is insufficient to restore mucosal immune homeostasis. This review summarizes the pathogenic processes that distinguish RCeD-I from RCeD-II and link failed mucosal recovery after gluten withdrawal to persistent immune-mediated epithelial injury, aberrant IEL expansion, clonal evolution, and lymphoma progression. Full article