Search Results (6,448)

Background: Spinal cord injury (SCI) triggers secondary injury processes involving neuroinflammation and systemic immune remodeling. The endocannabinoid system (ECS) has been implicated in neuroimmune regulation, but its transcriptional relationship with immune remodeling and its translational relevance in human SCI blood remain incompletely defined. Methods: A cross-species discovery–validation–translation framework was applied using a rat spinal cord discovery cohort (GSE45006), an independent mouse validation cohort (GSE171441), and a human peripheral white blood cell cohort (GSE151371). Analyses included differential expression profiling, ECS-focused assessment, cross-species comparison, immune-cell signature scoring, ECS–immune correlation analysis, receiver operating characteristic (ROC) analysis, LASSO-based biomarker prioritization, network analysis, disease enrichment, drug–gene interaction querying, and transcription factor/microRNA regulatory annotation. Results: ECS-related transcriptional remodeling was identified across rodent and human datasets in a compartment-dependent manner. In human SCI blood, CNR2, PTGS2, and DAGLB were significantly altered and showed biomarker-prioritization potential. Human SCI blood also showed innate immune enrichment, adaptive immune depletion, and significant ECS–immune correlations. The integrated 28-gene SCI–ECS immune panel formed a functionally coherent protein–protein interaction (PPI) network enriched in immune-response pathways. Disease enrichment supported an immune/inflammatory pathological context, whereas DGIdb identified hypothesis-generating drug–gene relationships involving ECS-related targets. ChEA 2022 revealed nominal transcription factor annotations that did not survive multiple-testing correction, and miRNet identified database-derived miRNA regulators of panel genes. In a secondary sensitivity analysis, the combined ECS signature also retained discriminatory performance against non-CNS trauma controls, suggesting that the observed transcriptional pattern was not fully attributable to generalized trauma-related responses. Conclusions: This study proposes an ECS-associated immune remodeling signature in SCI with translational biomarker-prioritization and pharmacologic target-annotation context in human peripheral blood. These findings are exploratory and require prospective and functional validation. Full article

Introduction: Pituitary carcinoma (PC) is a rare, aggressive endocrine neoplasm characterized by metastasis and challenging clinical management. The transformation from pituitary adenoma (PA) to PC is poorly understood, and predictors of metastasis remain elusive. This study evaluates the clinical course, surgical outcomes, and molecular characteristics of PC. Methods: We retrospectively reviewed patients with PC treated at the M. D. Anderson Cancer Center between 1993 and 2023. Primary outcomes included metastasis-free survival and overall survival (OS). Clinical features, radiographic findings, surgical strategies and outcomes, immunohistochemical profiles, and MIB-1 were analyzed. Results: The cohort (n = 20) had a median age at PA and PC diagnosis of 33.9 and 43.3 years, respectively. The median metastasis-free interval was 7.4 years. GH- and ACTH-secreting tumors showed shorter times to PC diagnosis, while nonfunctioning PAs had longer metastasis-free survival. PAs with MIB-1 > 10% had shorter survival. Dura was the most common site of metastasis within the CNS, and bone was the most common outside the CNS. Leptomeningeal disease was seen in six patients. PAs became aggressive > five years after initial surgical resection (n = 13) or metastasized early within the first five years (n = 7). Median OS from PA diagnosis was 13.7 years, and 8.6 years from PC diagnosis. A total of 102 neurosurgical procedures were performed, with a median of five per patient; the median was similar in patients surviving longer than five years vs. those whose survival was shorter (5.0 vs. 4.5 procedures, p = 0.661). Most surgical interventions post-PC diagnosis were for optic decompression or metastasectomy. All long-term survivors (at least five years after PC diagnosis) received temozolomide-based therapy, with most also receiving radiotherapy. Conclusions: PC shows a variable clinical course, with some PAs progressing to PC after years, while others transform rapidly. All long-term survivors received temozolomide-based therapy, most in combination with radiotherapy and repeated surgical intervention, suggesting that aggressive multimodal management may be associated with prolonged survival. Future research will focus on identifying reliable predictors of metastasis at different time points in the complex clinical evolution of these tumors. Full article

Fish are an important criterion for evaluating the quality of river ecosystems, and water flow characteristics may be the main factor affecting the living environment of fish. As the main component of a river, the topography of the bank slope has a significant impact on the characteristics of nearshore water flow. At the same time, eco-revetment structure has the functions of smoothing water flow, maintaining stable bank slopes, and improving river ecology. It can reset the distribution of nearshore water flow and provide a stable living environment for fish. This study focuses on the middle and lower reaches of the Yangtze River as the research area, with the main research object being grass carp. We construct a generalized model based on river morphology and flow characteristics. A new eco-revetment structure is proposed with the main research area of nearshore waters, aiming to improve the flow state of nearshore water and enhance its ecology. A suitability evaluation model for grass carp habitat was constructed based on Large Eddy Simulation and fuzzy mathematics theory, with water flow as the main habitat influencing factor. We study the distribution pattern of suitability for grass carp habitats near nearshore waters. The results indicate that the nitrogen phosphorus ratio near the top of the revetment structure is close to the Redfield value and can be used as a stable foraging area for fish. The flow rate is the dominant factor for the habitat of juvenile grass carp. When there is no vegetation, the suitability of region A is 0–0.4, the suitability of region B is 0.2–0.6, and the area proportion of the high suitability area (0.4–0.6) is maintained at 10–30% with the increase in the flow rate. Region C is not suitable for the long-term survival of juvenile grass carp. When there is vegetation, the suitability of region A ranges from 0 to 0.6, and the proportion of low-suitability areas decreases. The suitability of region B ranges from 0.4 to 0.6, and the proportion of suitable areas is positively correlated with flow velocity. The suitability of region C is consistent with the absence of vegetation. The dominant factors for fish spawning habitat are flow velocity, vorticity, and kinetic energy gradient. The spawning suitability zone (HSI ≥ 0.6) is located between the spanwise structures, with a proportion positively correlated with flow velocity and higher suitability on the deep-water side. The existence of fish has little impact on the habitat. In the juvenile fish habitat area, the proportion of areas suitable for juvenile fish in region A has slightly decreased, and the suitability of region B has increased. In spawning grounds, an HSI ≥ 0.6 accounts for about 5% of the decrease compared to no-fish conditions, and overall can meet the needs of fish habitat, foraging, and spawning. This article provides ideas and foundations for the design of future new eco-revetment structures and a suitability analysis of living environments for fish. Full article

Nectin-4 has emerged as a clinically relevant target in muscle-invasive bladder cancer (MIBC), primarily because of its role in antibody–drug conjugate-based therapies. However, the broader biological context of Nectin-4 expression and its association with tumor-promoting signaling pathways in MIBC remain insufficiently characterized. In this single-institution study, Nectin-4 expression (H-score 0–300) was assessed by immunohistochemistry in two independent MIBC cohorts. Associations between Nectin-4 expression and key markers related to growth signaling, metabolic regulation, and inflammation were analyzed alongside clinicopathological characteristics. Nectin-4 expression was significantly higher in malignant tissue than in non-malignant tissue (p = 0.0016 and p = 0.0302, respectively). Nectin-4 expression was not associated with demographic or clinicopathological parameters; however, a trend toward lower expression in more advanced disease stages was observed. Significant positive correlations were identified between Nectin-4 expression and protein kinase B (p = 0.0004), cytoplasmic (p = 0.0115) and membranous somatostatin receptor 2 (p = 0.0125), insulin receptor substrate 1 (p = 0.03), and interleukin-1 receptor antagonist (IL-1RA; p = 0.0045). In contrast, a negative correlation was observed with the IL-1β/IL-1RA ratio (p = 0.0246). Although Nectin-4 expression was not significantly associated with cancer-specific or overall survival, a trend toward shorter relapse-free survival was observed in patients with lower Nectin-4 expression (p = 0.0531). In multivariate analysis, patient age, but not Nectin-4 expression, emerged as an independent prognostic factor. Although Nectin-4 expression does not appear to have independent prognostic value, its biological associations suggest that it reflects an integrated tumor-related signaling context. These findings support further investigation of Nectin-4 as part of rational, biology-driven therapeutic strategies in bladder cancer. Full article

Objectives: Skeletal muscle architecture (SMA) defines the mechanical limits of force production. However, its associations with force–time strategy under externally loaded conditions have received little research attention. This exploratory study examined associations between vastus lateralis (VL) and lateral gastrocnemius (LG) architecture and force–time strategy, jump-height retention, and stretch–shortening cycle (SSC) transfer-efficiency in collegiate basketball players. Methods: Seventeen collegiate male basketball players completed B-mode ultrasonographic assessment of VL and LG architecture, including muscle thickness, pennation angle (PA), and fascicle length. Athletes performed the squat jump (SJ), loaded squat jump (LSJ), countermovement jump (CMJ), and loaded countermovement jump (LCMJ) on force platforms, with a 20 kg external load applied for loaded conditions. Loaded retention, defined as the percentage of jump height preserved under load, was proposed as a unified construct. Pearson’s correlations were calculated, with Benjamini–Hochberg false discovery rate (FDR) corrections applied within predefined functional groups and pooled across morphology-sensitive correlations. Results: LG PA showed a large negative association with LCMJ rate of force development (r = −0.68 [−0.87, −0.30]) and a large positive association with LCMJ time to peak force (r = 0.68 [0.29, 0.87]), both surviving within-group FDR correction. VL PA was associated with eccentric acceleration time and concentric time across jump conditions (r = 0.52 to 0.61), interpreted as exploratory. Transfer-efficiency indices showed no significant associations with SMA, except for the LCMJ/LSJ concentric time ratio, which showed a moderate negative association with LG PA (r = −0.49 [−0.79, −0.01]). Conclusions: Resting muscle architecture was associated with the temporal and rate characteristics of force expression under load, rather than with the gross preservation of jump height. Integrating architectural assessment with loaded force–time profiling warrants further investigation as a means of characterizing individual force-development strategies. Full article

Background: BCMA-targeted Chimeric Antigen Receptor (CAR) T-cell therapy has revolutionized the treatment of Relapsed/Refractory Multiple Myeloma (RRMM). However, the disease is not curable and progression after CAR T-cell treatment remains a challenge. Clonal hematopoiesis, specifically mutations in the DNA damage response gene PPM1D, has been linked to therapy resistance and inferior survival in lymphoma patients undergoing cellular therapy. The impact of PPM1D mutations on MM patient outcome after CAR T-cell therapy remains undefined. Methods: We conducted a retrospective single-center study of 83 patients with RRMM patients treated with idecabtagene vicleucel or ciltacabtagene autoleucel between 2022 and 2025. Next-generation sequencing was performed on peripheral blood mononuclear cells collected prior to CAR T-cell infusion to identify PPM1D exon 6 mutations (variant allele frequency > 0.01). We analyzed associations between mutational status, clinical characteristics, toxicity, and survival. Results: PPM1D mutations were detected in 14.5% (12/83) of patients. PPM1D-mutated patients had fewer prior autologous stem cell transplantation compared to wild-type patients (50% vs. 82%, p = 0.02) and presented more advanced disease burden and adverse prognostic features (R-ISS stage III 58% vs. 20%, p = 0.05). Notably, PPM1D status did not impact initial efficacy; complete remission rates were comparable between groups (67% vs. 69%). However, PPM1D mutations were significantly associated with inferior progression-free survival (PFS) (median PFS: 6 months vs. 16 months, p = 0.04). Regarding toxicity, the mutated subgroup exhibited significantly higher rates of grade ≥2 cytokine release syndrome and a trend toward increased neurotoxicity (25% vs. 7%). Conclusions: PPM1D clonal hematopoiesis is frequent in RRMM and despite deep initial responses, patients harboring PPM1D mutations face a significantly higher risk of early relapse. PPM1D mutations may serve as a biomarker for poor durability of response and should be further evaluated in larger, prospective trials. Full article

Background and Objectives: Effective palliative care relies on accurate identification and management of symptoms, especially in patients referred for palliative radiotherapy (PRT). This study aimed to identify symptom clusters (SCs)—defined as ≥2 interrelated symptoms—in patients evaluated at a multidisciplinary Radiotherapy and Palliative Care (RaP) outpatient clinic, using the Edmonton Symptom Assessment System (ESAS). Materials and Methods: We retrospectively analyzed data from patients referred to the RaP clinic between February 2017 and April 2020. Demographic and clinical characteristics, including ESAS scores at first visit, were collected. SCs were identified with principal component analysis (PCA) and unsupervised k-means clustering (KMC), determining the number of SCs based on the maximum gap statistic and interpretability. Associations with ECOG performance status (PS), primary tumor and metastases site, and PRT administration were analyzed. Exploratory survival analyses were performed. Results: Among 215 patients (median age = 71 years; 53% male), the mean total ESAS score was 24.03 (SD = 15.28). PCA identified four SCs: SC_PCA1 (tiredness, drowsiness, dyspnea, malaise), SC_PCA2 (depression, anxiety), SC_PCA3 (nausea, loss of appetite) and SC_PCA4 (pain). KMC revealed three SCs: SC_KMC1 (pain, tiredness, drowsiness, malaise), SC_KMC2 (nausea, loss of appetite, dyspnea), and SC_KMC3 (depression, anxiety). Worse ECOG PS correlated with physical SCs (p < 0.05). Psychological SCs were associated with lower likelihood of receiving PRT (OR_PCA2 = 0.26, CI: 0.07–0.80, OR_kmc3 = 0.19, CI: 0.02–0.85, p < 0.05), but when associated with pain/systemic clusters correlated with greater PRT use. A trend toward shorter survival was seen in SC_KMC2. Conclusions: SC analysis could improve personalized symptom management and clinical decision-making in the PRT setting. Full article

Hypoxia is a prevalent characteristic of neurological diseases, including ischemic injury, neurodegeneration and infectious disease complications. Concurrently, hypoxia shapes both protective and pathological responses within the central nervous system (CNS). Central to this process is hypoxia-inducible factor 1α (HIF1α), a transcription factor that regulates cellular adaptation to reduced oxygen availability through coordinated glycolytic, inflammatory and cell survival pathways. Under hypoxic conditions, HIF1α transcriptional activity influences microglial activation, mitochondrial quality control, and cytokine production, thereby modulating neuroinflammation and neuroprotection. Preclinical evidence points toward hypoxia preconditioning being neuroprotective through HIF1α-dependent mechanisms in a context-dependent matter. This review synthesizes the current understanding of the role of HIF1α across neurological disease contexts, highlighting the intersection of hypoxia, neuroinflammation and neuronal survival. Ultimately, defining the cell-specific and context-dependent involvement of HIF1α will be critical for targeted therapeutic approaches to alleviate neuronal death and slow disease progression. Full article

Background/Objective: During the last two decades, several cases presenting with circulating clonal B-cells with features consistent with possible marginal zone (MZ) derivation have been described under different terminologies. The present study aims to shed more light onto the main disease characteristics and determine prognostic factors for outcome in 98 consecutive cases with clonal B-cell lymphocytosis of marginal zone origin (CBL-MZ). Methods: This is a multicenter retrospective analysis including 98 consecutive CD5(−) CBL cases referred to our Departments between 1999 and 2017. These cases were selected based on the presence of circulating CD5(−) clonal B-cells, irrespectively of their absolute number, without B-symptoms, organomegaly, lymphadenopathy or cytopenias or any other features consistent with a known lymphoproliferative disorder. Clinical, morphologic, biochemical, immunophenotypic, histologic and molecular features of CBL-MZ cases were analyzed. Results: The median absolute lymphocyte counts (ALCs) and circulating CBLs were 6.7 × 10⁹/L and 3.447 × 10⁹/L, respectively. Paraproteinemia was found in 38%. Bone marrow (ΒΜ) was involved in all but one case. MYD-88L265P mutation was positive in 11%. Two subcategories of CBL-MZ were identified: One was characterized by lower ALC/CBL, paraproteinemia, CD38 expression, BM lymphoplasmacytic morphology and more frequent MYD-88L265P mutation. The second category displayed a leukemic picture, higher frequency of CD11c expression, hypogammaglobulinemia and elevated LDH. Treatment-free survival (TFS) was 91%, and median freedom from progression (FFP) was 95.6 months. For TFS, two factors proved significant using multivariate analysis: BM infiltration ≥ 50% and elevated LDH (RR 5.6 and 5.4, respectively). Evolution to splenic marginal zone lymphoma was a rare event (5%). A novel pattern of progression emerged, namely development of cytopenias due to extensive BM infiltration without any other disease localization. Conclusions: CBL-MZ is an indolent lymphoproliferative disorder with excellent outcome and low probability of progression. Based on our findings, CBL-MZ represents a heterogeneous entity where the vast majority of cases remain stable or develop increasing lymphocytosis. Clinically, our data also highlight that the extent of BM infiltration and elevated LDH levels appear to be the most notable predictors for introducing therapy. Full article

Background/Objectives: Intranasal tumors are common malignancies in dogs, characterized by locally aggressive behavior and clinical signs such as epistaxis, nasal discharge, and facial deformity. Radiotherapy (RT) is considered the treatment of choice due to anatomical limitations to surgical resection. This study aimed to evaluate clinical outcomes, toxicity, and prognostic factors in dogs with primary malignant intranasal tumors treated with cobalt-60–based megavoltage radiotherapy. Methods: This retrospective study included 40 dogs with histopathologically confirmed primary malignant intranasal tumors treated between September 2018 and February 2025 at a veterinary radiotherapy clinic in Rio de Janeiro, Brazil. Medical records were reviewed for patient demographics, tumor characteristics, treatment protocols, response, toxicity, and survival outcomes. Tumors were staged using modified Adams criteria based on computed tomography. Definitive-intent protocols (n = 32) delivered 48–54 Gy in 10–13 fractions administered three to five times weekly, while palliative protocols consisted of either four fractions of 8 Gy delivered once weekly or five fractions of 4 Gy delivered daily. Results: Adenocarcinoma was the most common histologic subtype (42.5%), and 82.5% of dogs had stage III–IV disease. The objective response rate was 82.5% (CR: 17.5%; PR: 65.0%), with clinical benefit observed in 92.5% of cases. Acute toxicity was frequent but manageable, primarily affecting skin, oral mucosa, and eyes. Overall median progression-free interval (PFI) and survival time (MST) were 382 days and 430 days, respectively. Stage IV disease was significantly associated with shorter survival when compared to stage I-III (MST 345 vs. 1063 days, respectively; p = 0.016). Treatment response was significantly associated with PFI in univariate analysis (p < 0.05). Conclusions: Radiotherapy provided high response rates and meaningful clinical benefit with acceptable toxicity in dogs with malignant intranasal tumors, highlighting the importance of early diagnosis and treatment. Further prospective studies with standardized protocols are warranted. Full article

Madhuca indica J.F.Gmel. holds significant economic and industrial value due to its applications in traditional and modern medicine. Its oil is especially important for biodiesel production, owing to its high acid value and suitability as a non-edible feedstock. However, propagation is difficult due to low seed germination, seed recalcitrance, and poor rooting of stem cuttings, limiting large-scale multiplication through conventional methods. To address these limitations, a regeneration protocol using nodal explants was developed. Murashige and Skoog (MS) medium augmented with BA (5.0 µM) and NAA (0.5 µM) produced a maximum of 7.10 ± 0.11 shoots per explant with an average shoot length of 4.53 ± 0.22 cm after six weeks. Rooting was achieved on half-strength medium supplemented with IBA (1.0 µM), resulting in 4.83 ± 0.17 roots per shoot and a root length of 4.50 ± 0.20 cm. In vitro-derived plants were successfully acclimatised in Soilrite with an 82.3% survival rate. The explants were derived from aseptic seedling material, representing juvenile rather than mature elite donor sources. Direct shoot bud development was verified by histological examination. Within the resolution of the employed marker systems, no polymorphism was found utilising RAPD and ISSR markers. SEM showed similar leaf surface characteristics, and physiological and biochemical studies were carried out throughout acclimatisation. A partial overlap in metabolite composition with qualitative and relative quantitative differences between mother and in vitro-derived plants was shown by GC–MS-based profiling. Overall, the study establishes a reproducible regeneration system for M. indica, providing a basis for further optimisation and conservation-oriented applications. Full article

The growing number of breast cancer survivors is expected to increase the absolute number of locoregional recurrences requiring management, necessitating improvements in treating recurrences or tumours that occur within the initial radiation field (IFR). However, there are no guidelines on reirradiation (RT2) for breast cancer IFRs. We aimed to investigate locoregional practice patterns and outcomes. We retrospectively identified patients who received adjuvant RT1 for resected breast cancer and subsequently received curative-intent RT2 for IFRs at two large tertiary centres. A chart review obtained treatment, patient, and tumour characteristics. Descriptive statistics were calculated to characterize practice patterns, toxicity, and survival outcomes. Thirty-five patients met inclusion criteria across 18 years, with mean follow-up time of 43 months. Median time from RT1 to progression was 70.1 months. Most IFRs were in the breast or chest wall alone (48.6%). Regional nodal irradiation (RNI) was given in 23% of RT1 and 48.6% of RT2. Complete field overlap occurred in 60% of patients. Ten patients (28.6%) had a second recurrence (i.e., after RT2). Five-year OS was 65.4%, the median OS was not reached, and the mean OS was 73.7 months (95% CI 59.8–87.7 months). Freedom from recurrence (after RT2) was 71%. Shorter time to initial recurrence was associated with second recurrence (p = 0.018), and second recurrence was found to be predictive of death (p < 0.001). Four (11.4%) patients developed fibrosis, 75% of which developed after RT1. Eight (22.9%) patients developed lymphedema, 75% of which developed after RT1, all of which were documented as stable after RT2. Managing breast cancer IFRs with RT2 appears to be a feasible approach with reasonably consistent practice patterns in appropriately selected patients. Toxicity appears to be driven by the initial treatment course, and survival outcomes are acceptable. Full article

Background/Objectives: This investigation was performed because corticosteroid injections are commonly used for symptomatic relief in patients with meniscal deficiency, yet their effect on graft survivorship and postoperative outcomes following meniscal allograft transplantation (MAT) remains poorly understood, with limited literature specifically addressing this topic. The aim of this study is to evaluate whether preoperative intra-articular corticosteroid injections (ICS) are associated with reoperation after MAT. Secondary aims included comparing reoperation-free survival, patient-reported outcome measures (PROMs), and patient acceptable symptom state (PASS) achievement. Methods: A retrospective review of 130 adults undergoing meniscal allograft transplantation (MAT) between 2011 and 2023 was performed. Patients with documented corticosteroid injection (CSI) status and ≥2 years of follow-up were included. Exclusion criteria included prior meniscal allograft transplantation, receipt of non-corticosteroid injections (e.g., hyaluronic acid or platelet-rich plasma), concomitant osteotomy procedures, multi-ligament knee reconstruction or inadequate follow-up. Propensity score matching (2:1 no steroid: steroid) based on age, sex, body mass index, fixation technique, operative compartment, and concomitant procedures yielded 54 matched patients (35 no steroid, 19 steroid). The primary outcome was ipsilateral knee reoperation, categorized as major reoperation (revision MAT, anterior cruciate ligament reconstruction, osteochondral allograft transplantation, conversion to total knee arthroplasty, meniscectomy and meniscus repair). Minor reoperations included irrigation and debridement, lysis of adhesions or manipulation under anesthesia, hardware removal, chondroplasty, and synovectomy. Reoperation-free survival was assessed using Kaplan–Meier analysis. PROMs and PASS were compared using adjusted regression models. Statistical significance was set at p < 0.05. Results: Baseline characteristics and follow-up were comparable between groups (7.6 ± 3.5 vs. 6.6 ± 3.2 years; p = 0.30). Overall reoperation occurred in 37.1% of patients in the no-steroid group and 31.6% in the steroid group (p = 0.771). Major reoperation rates were similar (17.1% vs. 15.8%; p = 1.000. There was no significant difference in minor reoperations between groups (20.0% vs. 10.5%; p = 0.468). Kaplan–Meier analysis demonstrated no difference in reoperation-free survival (p = 0.903), with comparable survival at the 1-, 2-, and 5-year time points. No individual subtypes differed significantly between groups. PROMs and PASS achievement were also similar, with no statistically significant differences observed. Conclusions: Preoperative corticosteroid injection was not associated with increased reoperation risk, inferior reoperation-free survival, or worse patient-reported outcomes following meniscal allograft transplantation. However, given the study’s limited power, lack of detailed injection characteristics, and the use of a heterogeneous complication outcome, these findings should be interpreted cautiously, as further investigation is warranted. Full article

Background/Objectives: Immunotherapy has emerged as an important field of research in non-small-cell lung cancer (NSCLC) and has demonstrated promising results in clinical practice. In recent years, multiple studies have been conducted, increasing the amount of available data. Therefore, the aim of this systematic review is to assess the combination of perioperative immunotherapy with chemotherapy compared to chemotherapy only in patients with resectable NSCLC in terms of survival, pathological response, and adverse events. Methods: The clinical databases PubMed, Cochrane Library, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) were systematically searched, up to March 2026. A two-step selection process served as the screening for eligibility, in which the assessment was based on pre-defined inclusion and exclusion criteria. This process was visualized via a PRISMA diagram. For each included study, the risk of bias was assessed with the help of the Cochrane Risk of Bias 2.0 tool and the Newcastle Ottawa Scale. A narrative synthesis was performed due to heterogeneity. Data were extracted into tables. Results: A total of 16 studies, involving 4646 patients in total, met the eligibility criteria, and their data on study population, intervention, comparison, and outcome were extracted into tabular form. Survival and pathological response rates are continuously higher in patients treated with immunochemotherapy. Findings on adverse events differed across the individual studies, though the results indicate an increased risk of treatment-related adverse events (TRAEs) in patients undergoing the combined treatment approach. Discussion/Conclusions: Chemoimmunotherapy leads to superior clinical outcomes in terms of survival and pathological response rates, though the trend towards a higher incidence and severity of TRAEs warrants further research. The interpretation of findings is limited by differences in study characteristics, mechanism of conduct, and endpoints between the individual studies. Full article

Background/Objectives: Patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) are vulnerable to rapid nutritional deterioration. The clinical relevance of short-term nutritional change during the diagnostic-to-treatment interval (DTI) remains unclear. In this study, we evaluated whether a dynamic change in the Geriatric Nutritional Risk Index (ΔGNRI) during the DTI is associated with treatment tolerability, treatment continuity, and survival. Methods: This single-center retrospective study included 120 patients with histologically confirmed UR-PDAC who initiated first-line palliative chemotherapy between January 2016 and April 2024. ΔGNRI was defined as the GNRI immediately before chemotherapy minus the GNRI at the initial visit. ΔGNRI was primarily analyzed as a continuous variable, and an exploratory cut-off value of −6.8 was determined by receiver operating characteristic analysis. One-to-one propensity score matching was performed as a sensitivity analysis. Clinically significant adverse events (AEs) were defined as grade ≥3 AEs or AEs requiring treatment modification, hospitalization, or treatment discontinuation. Results: Patients in the GNRI-decreased group had more frequent clinically significant non-hematologic AEs, including gastrointestinal AEs, higher hospitalization rates due to AEs, and more frequent early treatment discontinuation. ΔGNRI remained independently associated with early treatment discontinuation and failure to transition to second-line therapy in multivariable analyses. Patients in the GNRI-decreased group also had significantly shorter times to treatment failure and overall survival. These findings were consistent in propensity score-matched analyses. Conclusions: Dynamic nutritional decline during the DTI was associated with impaired treatment resilience and poor survival outcomes in UR-PDAC. ΔGNRI may help identify patients with emerging nutritional vulnerability before chemotherapy. Full article