Search Results (310)

Background/Objectives: Primary cardiac sarcomas are rare and aggressive tumors. Management is often guided by evidence from other sarcoma types due to limited disease-specific data. This study aimed to analyze the clinical characteristics, pathology, treatment, and outcomes of primary cardiac sarcomas at a national referral center in Spain. Methods: We conducted a retrospective, observational, single-center study from February 2017 to December 2024. Patient data were collected from medical records, and a descriptive analysis was performed. Results: Twelve patients were identified (58% female; median age 43 years, range 13–76). Dyspnea was the most common symptom (8/12, 67%), and the right atrium was the most frequent tumor site (6/12, 50%). Angiosarcoma was the predominant histologic subtype (6/12, 50%). Seven patients had localized disease at diagnosis. Surgery was performed in six patients, with complete (R0) resection in two. Two patients received adjuvant chemotherapy, one underwent cardiac transplantation, and one received sequential chemo- and radiotherapy. All patients experienced tumor recurrence, with a median recurrence-free survival of 5 months (95% CI, 1.5–8.6). Median overall survival for localized disease was 22 months (95% CI, 16–28). Five patients were metastatic at diagnosis, and 11 of 12 developed metastases. Median progression-free survival for first-line therapy was 5.9 months (95% CI, 1.8–9.9), and median overall survival for advanced disease was 12 months (95% CI, 10–13.6). Conclusions: Complete surgical resection was rarely achieved, and recurrence was universal. Outcomes remained poor even for localized disease, highlighting the limited efficacy of current therapies and the need for improved multimodal treatment strategies. Full article

Up to 25% of stage II colorectal adenocarcinomas recur within the first five years after diagnosis. The assessment of the stromal percentage, recently incorporated into the TNM classification system, may represent a particularly relevant predictive factor for recurrence in cases with microsatellite stability. We evaluated disease-free survival (DFS) in an independent retrospective cohort, measured the stromal percentage across the entire invasive front of the tumor, and assessed the interobserver agreement of this measurement method. Among 131 cases, 16 (12.2%) showed a high stromal percentage and 115 (87.8%) a low one. A high stromal percentage was associated with high-grade budding (p = 0.006). The 5-year DFS was 57% for high-stroma cases versus 76% for low-stroma cases (p < 0.001). Lymphatic invasion (HR: 16.513; p < 0.001) and a high stromal percentage (HR: 4.366; p = 0.006) had a statistically significant correlation with DFS. Interobserver agreement for global stromal assessment was very good (kappa index = 0.870; p < 0.001). In conclusion, the stromal percentage may be a predictive factor for recurrence, particularly relevant in stage II microsatellite-stable colorectal adenocarcinomas. Global stromal assessment appears to be a simple and easily reproducible method. Full article

Background: Obstructive sleep apnea (OSA) is a highly prevalent disorder associated with increased morbidity and mortality. Continuous positive airway pressure (CPAP) remains the first-line therapy, but its long-term effectiveness is limited by suboptimal adherence, with only 50–60% of patients achieving the recommended use. Evidence on adherence with alternative modalities, such as bilevel positive airway pressure (BiPAP) or oxygen therapy, is even more limited. Furthermore, few studies have directly compared these treatments with each other, particularly in relation to survival outcomes. Objective: Evaluate 5-year survival in patients with OSA treated with CPAP, BIPAP, or oxygen therapy. Methods: A retrospective cohort study with survival analysis was conducted in subjects with OSA followed at a tertiary-level institution in Colombia between January 2005 and December 2021. Results: Among 3039 patients with OSA (mean age 59.6 years; 59.8% male), the five-year mortality rate was 5.8%. Deceased patients presented a higher prevalence of comorbidities, including hypertension, diabetes, and cardiovascular disease (all p < 0.001). Adherence to CPAP was significantly lower in deceased patients. Survival analysis showed the highest five-year survival among adherent CPAP/Auto-CPAP users (95.6%), followed by non-adherent CPAP (95%) and adherent BiPAP users (94.1%). Lower survival was observed in non-adherent BiPAP users (91.7%) and oxygen therapy patients (80.6%). In multivariable analysis, treatment type, older age, congestive heart failure, chronic lung disease, and metastatic cancer were independently associated with increased mortality risk. Conclusions: Five-year survival in patients with obstructive sleep apnea was significantly associated with the treatment modality and adherence level. Full article

This study analyzes the temporal evolution of citations received by academic articles in the field of micro, small, and medium-sized enterprises (SMEs) and internationalization processes, with the aim of identifying patterns of growth and decline in scientific visibility. Based on a dataset of 1936 articles retrieved from Scopus, we constructed an article–year panel that enabled the application of multiple statistical approaches. Discrete-time survival models showed that the annual probability of receiving at least one citation is initially low, increases slightly until the fifth year, and then declines progressively thereafter. Negative binomial regression confirmed significant growth during the first five years, followed by a slowdown. Kaplan–Meier estimations reinforced this finding by showing that the cumulative proportion of articles receiving their first citation within a decade remains limited. These results confirm that citation dynamics are nonlinear and subject to early obsolescence, with most visibility concentrated in the short term. Importantly, this temporal bias in indexing and evaluation systems disproportionately favors recent publications while undervaluing older but still influential research. Such structural bias has profound implications for visibility and equity in scholarly communication, especially for disciplines and regions where citation cycles are longer. The findings thus validate the study’s propositions: first, that citation growth slows significantly after the fifth year, and second, that this slowdown represents a structural bias that amplifies inequities in research evaluation. Full article

Acute myeloid leukemia (AML) continues to carry a dismal prognosis in older adults and those with secondary or high-risk disease, where conventional 7 + 3 chemotherapy has long delivered complete remission rates below 40% and median overall survival often under 6 months. CPX-351 (Vyxeos), a liposomal co-encapsulation of cytarabine and daunorubicin at a fixed synergistic 5:1 molar ratio, was designed to overcome the pharmacokinetic mismatch that undermines the traditional regimen. This review critically examines the preclinical rationale and clinical evidence for CPX-351, with particular attention to whether its nanoparticle platform truly represents a breakthrough or merely an incremental refinement of decades-old cytotoxics. Across phase I–III trials and real-world cohorts, CPX-351 consistently outperformed standard 7 + 3 in its approved populations of newly diagnosed therapy-related AML (t-AML) and AML with myelodysplasia-related changes (AML-MRC) in patients aged 60–75 years. In the pivotal phase III study (n = 309), CPX-351 improved median overall survival from 5.95 to 9.56 months (HR 0.69, 95% CI 0.52–0.90; p = 0.005) and raised the complete remission rate from 33.3% to 47.7%, while facilitating allogeneic transplantation in 34% as opposed to 25% of patients. A five-year follow-up sustained the separation in survival curves, and post-hoc analyses of responders showed median overall survival exceeding 25 months with CPX-351 versus approximately 10 months with 7 + 3 (HR 0.49). Real-world series have reported composite remission rates of 53–60%, measurable residual disease negativity in up to 65% of responders, and median overall survival of 12–20 months, depending on transplant utilization. Despite these gains, the absolute survival benefit remains modest, prolonged cytopenias are universal, and outcomes in TP53-mutated or younger adverse-risk patients are still poor, raising legitimate questions about cost-effectiveness and generalizability. Nonetheless, CPX-351 stands as the first clinically validated example of ratiometric nanomedicine in oncology, proving that reformulating established drugs can yield meaningful progress where novel agents have often failed. Full article

Background: Neurological disorders are the leading cause of disability, affecting over three billion people worldwide. Amyotrophic lateral sclerosis (ALS) is among the most feared and uniformly fatal neurodegenerative diseases, with no therapy capable of restoring lost function. Methods: We report the first application of therapeutic fever to ALS using Computerized Brain-Guided Intelligent Thermofebrile Therapy (CBIT²). This fully noninvasive treatment, delivered through an FDA-approved computerized platform, digitally reengineers the 1927 Nobel Prize-recognized malarial fever therapy into a modern treatment guided by the Brain–Eyelid Thermoregulatory Tunnel. CBIT² induces therapeutic fever through synchronized hypothalamic feedback, activating heat shock proteins, which are known to restore proteostasis and neuronal function. Case presentation: A 56-year-old woman was diagnosed with progressive ALS at the Mayo Clinic, with electromyography (EMG) demonstrating fibrillation and fasciculation indicative of denervation corroborated by neurological and MRI findings; the patient was informed that she had an expected survival of three to five years. A neurologist from Northwestern University confirmed the diagnosis and thus maintained the patient on FDA-approved ALS drugs (riluzole and edaravone). Her condition rapidly worsened despite pharmacological treatment, and she underwent CBIT², resulting in (i) electrophysiological reversal with complete disappearance of denervation; (ii) biomarker correction, including reductions in neurofilament and homocysteine, IL-10 normalization (previously linked to mortality), and robust HSP70 induction; (iii) restoration of gait, swallowing, respiration, speech, and cognition; (iv) reconstitution of tongue structure; and (v) return to complex motor tasks, including golf, pickleball, and swimming. Discussion: This case provides the first documented evidence that ALS can be reversed through digitally reengineered fever therapy aligned with thermoregulation, which induces heat shock response and upregulates heat shock proteins, resulting in the patient no longer meeting diagnostic criteria for ALS and discontinuation of ALS-specific medications. Beyond ALS, shared protein-misfolding pathology suggests that CBIT² may extend to Alzheimer’s, Parkinson’s, and related disorders. By modernizing this Nobel Prize-recognized therapeutic principle with computerized precision, CBIT² establishes a framework for large-scale clinical trials. A century after fever therapy restored lost brain function and so decisively reversed dementia paralytica such that it earned the 1927 Nobel Prize in Medicine, CBIT² now safely harnesses the therapeutic power of fever through noninvasive, intelligent, brain-guided thermal modulation. Amid a global brain health crisis, fever-based therapies may offer a path to preserve thought, memory, movement, and independence for the more than one-third of humanity currently affected by neurological disorders. Full article

Background: Coronary artery bypass grafting (CABG) is a widely used procedure to treat coronary artery disease, performed either alone or in conjunction with other cardiac procedures. Perioperative myocardial infarction (pMI) remains a major complication after on-pump CABG and negatively influences survival. Its reported incidence varies with the applied definition, and little is known about its prognostic effect in combined surgeries. Objective: The aim of this study was to investigate the impact of pMI on 5-year survival after isolated or combined on-pump CABG. Methods: We retrospectively reviewed adult patients undergoing urgent or elective CABG with cardiopulmonary bypass at Amiens University Hospital between 2013 and 2017. Diagnosis of pMI followed the Fourth Universal Definition of myocardial infarction. The primary outcome was all-cause death within 5 years. Logistic regression and Cox proportional hazards analyses were performed, and inverse probability weighting based on propensity scores was used to minimize confounding. Results: Out of 712 patients, 112 (16%) experienced pMI. Five-year mortality was 32% in the pMI subgroup compared with 11% in those without pMI (p < 0.001). Before adjustment, pMI was associated with higher long-term mortality (HR = 2.62, 95%CI [1.73–4.00], p < 0.001). This effect persisted after weighting (HR = 2.43, 95% CI [1.56–3.78], p = 0.041). A landmark analysis excluding the first 30 postoperative days showed no significant link with later mortality (HR = 1.13, 95%CI [0.54–2.34], p = 0.74). Independent predictors of pMI included active smoking (OR = 2.24, 95% CI [1.36–3.69], p = 0.001) and prolonged bypass duration (>180 min) (OR = 2.57, 95% CI [1.19–5.34], p = 0.015). Conclusions: When defined by the Fourth Universal Definition, pMI was independently related to increased 5-year mortality following CABG, explained mainly by deaths occurring early after surgery. Full article

Background and Objectives: Pancreatic neuroendocrine tumors (PanNETs) are rare and heterogeneous neoplasms with variable clinical behavior. Despite advances in diagnosis and treatment, the optimal management strategy remains unclear. This present study aims to evaluate survival outcomes according to first-line therapy and tumor characteristics. Materials and Methods: We conducted a retrospective cohort study including adult patients with histologically confirmed PanNETs who were treated at a tertiary care center between January 2020 and January 2025. Patients were divided into two groups according to their first-line management: surgical resection or non-surgical treatment. Overall survival (OS) was assessed in the entire cohort, and disease-free survival (DFS) was evaluated in patients who underwent complete surgical resection (R0). Results: A total of 68 patients were included, of whom 46 (67.6%) underwent surgery as first-line treatment. In the non-surgical group, 45.5% received combined systemic therapy and somatostatin analogues (SSA), 36.4% received SSA alone, 4.5% systemic therapy alone, and 9.1% were managed with active surveillance. Patients who underwent surgery tended to have lower-grade tumors and earlier-stage disease. The OS rates were 96.5% at one year, 83.2% at three years, and 62.3% at five years, with a median OS of 179 months. Both surgical treatment and lower tumor grade were significantly associated with improved OS. Among patients who had R0 resection, DFS was 95.8% at one year and 84.3% at both three and five years. Lower-grade tumors were also associated with longer DFS. Conclusions: This study demonstrates that first-line surgical resection and lower tumor grade were significantly associated with better OS in patients with PanNETs. Among patients who underwent curative surgery, lower tumor grades were associated with improved DFS. Full article

No validated biomarkers are available to monitor neoadjuvant treatment effects for breast cancer. Natural killer cell activity (NKA) has shown prognostic potential in other cancers. This study examined the association between NKA and treatment response. Patients had blood samples collected at baseline, before each treatment, and pre- and postoperatively. Plasma IFNγ levels were measured by ELISA as a surrogate marker of NKA, with 250 pg/mL as the cutoff for normal versus low NKA. Study endpoints were residual cancer burden (RCB) class, overall survival (OS), and invasive disease-free survival (IDFS). Seventy-eight patients were included. The five-year IDFS was 88.1% (95% confidence interval (CI) 73.7–94.9%) for patients with normal NKA versus 71.5% (95% CI 40.6–88.2%) for patients with low NKA (p = 0.049) preoperatively. At the fifth treatment cycle, the median IFNγ was 11 pg/mL (interquartile range (IQR) 0.5–124 pg/mL) in patients receiving supportive prednisolone and 753 pg/mL (IQR 192–1580 pg/mL) in patients not receiving supportive prednisolone. At the sixth treatment cycle, the corresponding values were 7 pg/mL (IQR 0–15 pg/mL) and 806 pg/mL (IQR 180–1631 pg/mL) (p < 0.0001). In conclusion, NKA may have prognostic potential as a biomarker. This study is the first to demonstrate that prednisolone impairs NKA measurement in breast cancer patients. Full article

Background/Objectives: In Spain, pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related death, with only 20% of patients eligible for surgery at diagnosis. For the remaining majority, prognosis is poor and effective non-surgical strategies are needed. Stereotactic MR-guided adaptive radiotherapy (SMART) may facilitate the delivery of ablative doses of radiation safely with low toxicity. This study reports the first national experience in Spain with SMART for patients with borderline resectable (BRPC) or locally advanced pancreatic cancer and evaluates its feasibility, safety, and early clinical outcomes. Methods: A prospective observational study was conducted including 28 patients with histologically confirmed BRPC or LAPC treated between August 2023 and December 2024. All patients received induction chemotherapy—mainly FOLFIRINOX (57.1%)—followed by SMART delivered in five fractions (40–50 Gy) using a 0.35T MR-guided linear accelerator. Daily online adaptive recontouring and replanning were performed for all 140 treatment fractions. Toxicities were assessed using CTCAE v5.0, and survival outcomes were estimated using Kaplan–Meier analysis. Results: The median patient age was 67 years, and 71.4% of tumors were located in the pancreatic head. At a median follow-up of 7.4 months after SMART (12.25 months from diagnosis), 6-month local progression-free survival (LPFS) was 89.3% from the start of SMART and 82.1% from diagnosis. Distant progression-free survival (DPFS) at 6 and 12 months was 92.9% and 68.2%, respectively. Median progression-free survival (PFS) was 11.5 months, and the median treatment-free interval was 5.7 months. Median overall survival (OS) was not reached; 6- and 12-month OS rates were 89.3% and 74.1%, respectively. Treatment-related toxicity was limited to grade 2 abdominal pain in 14.3% of patients, with no grade ≥3 adverse events attributed to SMART. Conclusions: SMART is a feasible and safe treatment modality for BRPC and LAPC in real-world clinical practice. These encouraging early outcomes support further clinical investigation and broader implementation. Full article

Background/Objectives: The anti-GD2 monoclonal antibody dinutuximab beta has become standard of care maintenance therapy for high-risk neuroblastoma (HR-NB) in the first-line setting and is also approved in the relapsed/refractory setting. We present a retrospective review of 37 children with HR-NB included in the Hungarian Childhood Cancer Registry who received dinutuximab beta (first-line maintenance therapy, n = 31; relapsed/refractory, n = 6). Methods: All patients received dinutuximab beta continuously over the first 10 days of each 35-day cycle, with dosing based on body surface area/weight. Five cycles were planned, with further cycles administered at the treating physician’s discretion. Results: At data cutoff, the overall disease control rate was 54.1% (20/37) (complete response, 51.4% (19/37); partial response, 0.0% (0/37), stable disease, 2.7% [1/37]); two patients (5.4%) had progressive disease, and 15 patients (40.5%) had died. The 5-year overall survival (OS) and event-free survival (EFS) rates in the overall population were 63.3% (95% confidence interval, 49.1−81.7) and 56.2% (95% confidence interval, 42.1−75.0), respectively. Grade 3 or 4 adverse events (including blood and lymphatic system disorders, hypoxia, hypotension, and capillary leak syndrome) were generally consistent with dinutuximab beta’s known safety profile. Conclusions: Dinutuximab beta was an effective immunotherapy for patients with HR-NB in routine clinical practice, with a generally manageable side effect profile. Full article

Background: Significant changes in renal cell carcinoma (RCC) drug treatment and improved access to abdominal imaging have recently been implemented. The impact of these changes on patient characteristics and prognosis remains to be quantified. Methods: A population-based cohort of 210,418 RCC cases from the Centre for Cancer Registry Data (ZfKD) diagnosed in Germany between 2000 and 2019 was analyzed in this observational study. Three time periods of diagnosis were defined, the first (2000–2005) functioning as a control. The remaining were defined according to the introduction of tyrosine kinase targeting drugs (2006–2014) and checkpoint inhibitor drugs (2015–2019). Five-year relative survival (RS) trends for each risk group and metastatic RCC (mRCC) were determined using Poisson regression models. Results: Age at diagnosis and the proportion of low-risk disease increased, while the proportion of mRCC decreased (p < 0.0001). RS improved slightly between the first and last period in low (5-year RS 98.7% vs. 100.9%), intermediate (89.2% vs. 91.9%), and high-risk (76.6% vs. 80.3%), as well as mRCC (28.3% vs. 29.1%). The overall change in prognosis was significant in low (p = 0.0233) and high-risk groups (p = 0.0002), but not in intermediate-risk and mRCC groups. In a multivariate analysis, high-risk ccRCC patients appear to profit from drug treatment advances. Conclusions: Earlier detection has improved prognosis for the majority of RCC patients. Further efforts should be aimed at diagnosing more mRCC patients earlier, when surgical tumor removal remains feasible. Full article

Background: Chronic lung allograft dysfunction (CLAD) occurs in up to 50% of patients within the first five years after lung transplantation (LuTX) and represents the main complication and cause of death regarding this surgery. Alveolar septal widening in transbronchial biopsies has shown an association with acute humoral allograft rejection. We aimed to explore histological markers that could predict the development of CLAD before its clinical manifestation. Methods: We retrospectively analyzed transbronchial biopsies taken at three time points from 57 patients who underwent LuTX between February 2010 and July 2019, 26 of whom developed CLAD up to November 2022. The biopsies were analyzed by microscopic morphometry and quantitative reverse transcription PCR to identify predictors of CLAD. Results: CLAD development was associated with increased alveolar septal width (ASW) as early as the first year post-LuTX (5.46 ± 0.76 µm versus 4.59 ± 0.44 µm; p < 0.001). The ASW in later biopsy timepoints predicted survival in multivariate models (last timepoint: hazard ratio 1.885, 95% confidence interval 1.086–3.269). Collagen (COL1A1 and COL3A1) expression was significantly increased in samples from patients who developed CLAD compared with those who did not. The increase in ASW was paralleled by interstitial deposition of COL1A1 and COL3A1 and a decrease in both the carbon monoxide (DLCO) diffusing capacity of the lung and the DLCO/alveolar volume. Conclusions: We report a new histologic approach for early assessment of risk of CLAD in patients who have undergone LuTX. The ASW represents a pre-symptomatic, continuous, and widely distributed change within the lung parenchyma that is accessible to transbronchial biopsy. Full article

Objective: Sarcopenic obesity (SO) is a combination of depleted skeletal muscle mass and obesity, with a high prevalence, undetected onset, challenging diagnosis, and poor prognosis. However, studies on SO in cancer settings are limited. We aimed to explore the association between SO and mortality and to investigate potential predictors involved in the development of SO, with a further objective of constructing a model to detect its occurrence in cancer patients. Methods: The data of 1432 cancer patients from the National Health and Nutrition Examination Survey (NHANES) from the years 1999 to 2006 and 2011 to 2016 were included. For survival analysis, univariable and multivariable Cox proportional hazard models were used to examine the associations of SO with overall survival, adjusting for potential confounders. For machine learning, six algorithms, including logistic regression, stepwise logistic regression, least absolute shrinkage and selection operator (LASSO), support vector machine (SVM), random forest (RF), and extreme gradient boosting (XGBoost), were utilized to build models to predict the presence of SO. The predictive performances of each model were evaluated. Results: From six machine learning algorithms, cancer patients with SO were significantly associated with a higher risk of all-cause mortality (adjusted HR 1.368, 95%CI 1.107–1.690) compared with individuals without SO. Among the six machine learning algorithms, the optimal LASSO model achieved the highest area under the curve (AUC) of 0.891 on the training set and 0.873 on the test set, outperforming the other five machine learning algorithms. Conclusions: SO is a significant risk factor for the prognosis of cancer patients. Our constructed LASSO model to predict the presence of SO is an effective tool for clinical practice. This study is the first to utilize machine learning to explore the predictors of SO among cancer populations, providing valuable insights for future research. Full article

Background: Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy characterized by rapid growth, early metastatic dissemination, and a dismal prognosis. For decades, treatment paradigms remained largely stagnant, particularly for extensive-stage disease (ES-SCLC). However, the last five years have witnessed a significant evolution in the therapeutic landscape. Methods: The information for this article was gathered by synthesizing data from several key sources. This article synthesizes the evidence supporting current standards of care for both limited-stage (LS-SCLC) and ES-SCLC, incorporating data from pivotal clinical trials, a network meta-analysis of first-line chemoimmunotherapy regimens, and a critical appraisal of international treatment guidelines, and a critical analysis of international treatment guidelines from prominent organizations like the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO). This comprehensive approach allows for a robust and well-supported summary of the current therapeutic landscape. Results: For limited-stage SCLC (LS-SCLC), concurrent chemoradiotherapy (cCRT) remains the curative-intent standard, but its efficacy is now being augmented by consolidative immunotherapy, as demonstrated by the landmark ADRIATIC trial. The role of prophylactic cranial irradiation (PCI) in LS-SCLC is being re-evaluated in the era of high-sensitivity brain imaging and concerns over neurotoxicity. For ES-SCLC, the treatment paradigm has been fundamentally transformed by the integration of immune checkpoint inhibitors (ICIs) with platinum–etoposide chemotherapy, establishing a new standard of care that offers a modest but consistent survival benefit. Conclusions: The treatment of SCLC has been significantly advanced by the integration of immunotherapy, particularly for extensive-stage disease, which has established a new standard of care and improved patient outcomes. Looking to the future, the quest for predictive biomarkers and the development of novel therapeutic classes, such as Bi-specific T-cell Engagers (BiTEs) and antibody–drug conjugates, promise to build upon recent progress and offer new hope for improving the dismal prognosis associated with this disease. Full article