Search Results (158)

Background: Early excision and autologous split-thickness skin grafting are the cornerstone of surgical management in severe burn injuries. In patients with extremely extensive deep burns, the lack of available donor sites represents a major life-threatening limitation. In the exceptional situation of monozygotic twins, skin isografting offers a unique solution by providing immunologically compatible skin without the risk of rejection. Case report: We report the case of a 33-year-old man who sustained flame burns involving 95% of his total body surface area, resulting in an extremely poor initial prognosis (ABSI 14, UBS 245). After early resuscitation and staged surgical excisions, the absence of sufficient autologous donor sites precluded definitive coverage using conventional techniques. On day 3, the existence of a monozygotic twin brother was identified. HLA genotyping confirmed complete identity, and skin donation was authorized by an independent ethics committee. Methods: Definitive wound coverage was achieved using staged split-thickness skin isografts harvested from the donor twin. Ultra-thin grafts (<0.2 mm) were obtained in three procedures (days 7, 11, and 45), primarily from the scalp, thighs, and back, and applied following sequential excisions. Results: All grafts survived without immunological rejection. Donor-site morbidity was minimal, with rapid healing and only mild residual hypopigmentation. The patient was discharged to rehabilitation on day 145. At 5-year follow-up, wounds were fully healed, functional outcome was satisfactory, and quality of life was good, with return to work and full independence. Conclusions: Skin isografting from a monozygotic twin is a rare but effective salvage strategy for patients with massive deep burns when autologous donor sites are insufficient, provided that ethical, legal, and donor safety considerations are rigorously addressed. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major cause of cancer mortality worldwide. Because HCC usually arises in cirrhotic livers, prognosis is shaped by the dual threats of tumor progression and hepatic decompensation, requiring treatment decisions that balance anticancer efficacy with preservation of liver function, portal hypertension control, and quality of life. In recent years, management has shifted from a predominantly locoregional approach to an integrated continuum that spans curative resection, ablation, and transplantation; refined transarterial and radiotherapy techniques; and modern systemic therapy dominated by immunotherapy-based combinations. These advances have improved response rates, enabled downstaging and conversion in selected patients, and expanded opportunities for sequential and multimodal treatment. However, challenges persist, including therapeutic decision-making in patients with Child–Pugh B liver function, lack of robust predictive biomarkers, and resistance after initial response. Emerging tools—liquid biopsy, radiomics, AI-assisted imaging, and microbiome modulation—may support future precision strategies and optimized treatment allocation. In this review, we summarize current evidence guiding staging and therapy selection, outline practical considerations across curative, locoregional, and systemic modalities, and discuss evolving biomarkers and next-generation immunotherapy as key steps toward more personalized, durable, and equitable global HCC care. Full article

Objectives: Glioblastoma multiforme (GBM) is considered the most aggressive primary brain tumor, which often exhibits tumor heterogeneity. Hypoxia is a key aspect of intratumoral heterogeneity that contributes to poor prognosis in GBM. In this study, we aimed to develop machine learning (ML) models using radiomics and clinical features for the prediction of one-year survival for GBM. Methods: Data from 35 patients in the ACRIN 6684 trial, including fluoromisonidazole (FMISO)-positron emission tomography (PET), magnetic resonance (MR) (T1, T2, and fluid-attenuated inversion recovery (FLAIR)) images, and clinical information, were retrieved from The Cancer Imaging Archive (TCIA). Three ML algorithms, namely, support vector machine (SVM), random forest (RF), and linear regression (LR), were utilized to analyze selected features. Receiver-operating characteristic (ROC) curves were utilized to evaluate the predictive performance of the models. Several statistical analyses, namely, the permutation test, the permutation importance of selected features, Fisher’s exact test, and the unpaired t-test, were performed to analyze the models and features. Results: FMISO achieved the best performance in radiomics models, with an area under the curve (AUC) of 0.870. The clinical data model achieved the best performance of all models, with an AUC of 0.921, outperforming the combined all sequential forward selection (SFS) model (AUC: 0.862). Female sex (p = 0.030) and younger age (p = 0.0043) were significantly associated with better prognosis. Conclusions: Our proposed models have the potential to predict the one-year survival of GBM and facilitate personalized therapy. Future studies with a larger sample size are needed to confirm the generalizability of the models. Full article

Background/Objectives: Triple-negative breast cancer (TNBC) lacks targeted therapies and has a poor prognosis. Wild ginseng (Panax ginseng) is traditionally valued for its medicinal properties, but its scarcity limits therapeutic application. Adventitious root culture technology provides a sustainable source of wild ginseng-derived bioactive compounds. This study investigated the anticancer effects of wild ginseng adventitious root extract (WGAR) on MDA-MB-231 TNBC cells and elucidated the underlying molecular mechanisms. Methods: WGAR was prepared from cultured adventitious roots of 100-year-old wild ginseng, and its chemical composition was analyzed by LC-MS/MS. Anticancer effects were evaluated using MTT assay, acridine orange/propidium iodide (AO/PI) staining, Matrigel invasion assay, Western blot analysis, and proteome profiler array. Molecular docking was performed to predict interactions between WGAR constituents and target proteins poly (ADP-ribose) polymerase (PARP)-1 and β-catenin. Results: LC-MS/MS analysis tentatively identified 17 compounds, including ginsenosides (Rg3, Rh1, Rf) and terpenoids (ursolic acid). WGAR reduced cell viability with an IC50 of 79 μg/mL at 48 h, inducing 51.2% cell death. WGAR activated the intrinsic apoptotic pathway through sequential caspase-9 and caspase-3 activation, followed by PARP cleavage, and was associated with changes in epithelial–mesenchymal transition (EMT)-related markers (reduced N-cadherin, Slug, and β-catenin) alongside decreased inhibitory Ser9 phosphorylation of GSK-3β. Proteome array analysis revealed suppression of ECM remodeling proteins (tenascin C, u-PA) and inflammatory mediators (IL-6, CXCL8). Molecular docking predicted that selected WGAR constituents, particularly terpenoid-type compounds, may potentially interact with PARP-1 and β-catenin; however, these in silico findings are hypothesis-generating and require experimental validation. Conclusions: WGAR exerts multi-target anticancer effects on TNBC cells through apoptosis induction and EMT suppression associated with modulation of GSK-3β/β-catenin signaling, suggesting its potential as a source of therapeutic agents for TNBC. Full article

Background: Pancreatic cancer (PC) has a very poor 5-year survival and prognosis. Even when CT or MRI shows no metastasis, staging laparoscopy(SL) still detects tiny peritoneal deposits in 20–30% of patients, making them ineligible for surgery. SL is invasive, requiring general anesthesia and substantial resources. Endoscopic ultrasound (EUS) allows the observation of the bile ducts, pancreas, and abdominal cavity, and EUS-guided fine-needle aspiration (EUS-FNA) is essential for pathological diagnosis. Reports on using EUS to perform peritoneal lavage cytology are currently not available. We hypothesized that combining EUS-FNA with peritoneal lavage (EUS-lavage technique; EUS-LT) could enhance staging accuracy and avoid unnecessary surgical procedures. Methods: Ten in vivo porcine models underwent EUS-LT. Using a 19G FNA needle, 800 mL saline was instilled into the intraperitoneal cavity and then recovered. Two refinements were introduced sequentially: an ENBD catheter with additional side holes and, subsequently, a side-hole introducer (EndoSheather) that eliminated balloon dilation. The primary endpoint was procedural success. Secondary endpoints included safety, complications, recovered volume, duration of endoscopic procedure, and time required to instill 800 mL. Nonparametric tests compared outcomes across iterations. Results: Ten-model porcine in vivo model series were included, and all procedures were successful. No device malfunctions or unanticipated technical failures; one minor mucosal injury during saline injection resolved after re-puncture. The average procedure time was 31.1 min. Stepwise refinements shortened procedure and infusion times and increased recovered volume. Recovered volume approached the instilled amount in later cases, indicating efficient performance. Conclusions: In this ten-model in vivo series, EUS-LT demonstrated technical feasibility and short-term safety. Full article

Background: Severe sepsis and septic shock remain major causes of ICU mortality despite advances in critical care. Polymyxin B hemoperfusion (PMX-HP) is widely used in Asia for refractory endotoxemia, yet the optimal session strategy remains unclear. Methods: We retrospectively analyzed adult ICU patients with severe sepsis or septic shock treated with PMX-HP between 2013 and 2019 in a tertiary center in Taiwan. Patients were divided into sequential (≥2 sessions within 24 h) and non-sequential groups. The primary outcome was 28-day mortality; secondary outcomes included ICU and hospital mortality, length of stay, organ support, and vasoactive-inotropic score (VIS) changes. Results: Among 64 patients, 33 (51.6%) received sequential therapy. The 28-day mortality was 46.9%, with no difference between groups after adjustment for baseline severity. Patients receiving sequential PMX-HP had longer hospital stays and more frequent CRRT use, likely reflecting greater underlying disease severity rather than a causal effect of treatment sequencing. Conclusions: Multivariate analysis identified higher APACHE II score, positive VIS change, and CRRT requirement as independent predictors of mortality. Sequential therapy itself was not associated with improved outcomes. Prognosis in PMX-HP-treated patients is determined mainly by underlying severity and hemodynamic instability, underscoring the need for patient selection and biomarker-guided strategies rather than routine sequential use. Full article

Background and Clinical Significance: Kidney transplant recipients have a 2–4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. Case Presentation: A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. Conclusions: Vigilant post-transplant cancer surveillance—including native-kidney RCC—tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis. Full article

Background: Accurate prediction of survival in septic patients remains a major challenge in intensive care medicine. Established severity scores such as the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) are widely used to estimate prognosis, while biochemical markers such as serum lactate may provide complementary information. However, the prognostic interplay between these scores, lactate dynamics, vasopressor requirement, and infection focus has not been fully elucidated in septic populations. Methods: We conducted a retrospective observational study of 146 adult patients with sepsis admitted to the intensive care unit (ICU) of the Hospital Clínico Universitario de Valladolid (HCUV), Spain, between 2022 and 2024. Demographic data, APACHE II and SOFA scores at admission, lactate levels at admission and 24 h, albumin, and procalcitonin were recorded. Vasopressor use (categorized by intensity) and infection focus (urinary vs. non-urinary) were documented. The primary outcome was ICU mortality. Correlation analyses (Pearson or Spearman as appropriate) were performed separately for urinary and non-urinary subgroups. Multivariable logistic regression models were constructed using APACHE II, SOFA, log-transformed lactate at 24 h, vasopressor use, and urinary focus as predictors. Model performance was assessed using Nagelkerke R², area under the ROC curve (AUC), and classification accuracy. Results: ICU mortality was 23.3%. APACHE II (OR 1.092; p = 0.004) and SOFA (OR 1.185; p = 0.023) were independent predictors of ICU mortality, while log-transformed lactate at 24 h showed a positive trend (OR 1.920; p = 0.066). The addition of urinary focus (protective effect, OR 0.19; p = 0.035) and vasopressor requirement (OR 2.20; p = 0.04) modestly improved model discrimination (Nagelkerke R² = 0.395). ROC analyses showed AUCs of 0.800 for APACHE + SOFA + log-lactate, 0.824 for the vasopressor model, and 0.833 for the urinary focus model. The best-performing models achieved >85% overall accuracy, with specificity consistently above 95%. Conclusions: In septic ICU patients, APACHE II and SOFA scores remain independent predictors of ICU mortality, and lactate at 24 h adds prognostic value—particularly in non-urinary infections. Vasopressor requirement and infection focus modestly improved model discrimination, underscoring their clinical relevance. These findings suggest that integrating severity scores with selected metabolic and clinical variables may modestly refine survival prediction in septic patients. Full article

Background: Periodontitis and oral dysbiosis have been linked to systemic inflammation and carcinogenesis. Among oral pathogens, Porphyromonas gingivalis (Pg) and Fusobacterium nucleatum (Fn) are biologically plausible contributors to colorectal cancer (CRC) via inflammatory and immunomodulatory pathways. However, the magnitude and consistency of these associations remain uncertain. Objective: To evaluate whether periodontitis and key oral pathogens are associated with CRC risk and prognosis through a systematic review, meta-analysis, and trial sequential analysis (TSA). Methods: We searched PubMed, Scopus, and Web of Science from inception to December 2024 following PRISMA 2020. Eligible observational studies assessed periodontitis exposure or detection of oral bacteria in relation to CRC incidence or survival. Effect estimates (RRs/HRs) were log-transformed and pooled using random-effects models; heterogeneity was quantified with I². TSA was conducted to appraise information size and the stability of the primary association. Risk of bias was evaluated with ROBINS-I/QUIPS as appropriate. PROSPERO: CRD420251168522. Results: Five studies evaluating periodontitis/oral-pathogen exposure and CRC incidence yielded a 70% higher risk (HR = 1.70; 95% CI: 1.33–2.19; I² = 0%). Detection of Fn was associated with approximately threefold higher risk of CRC (RR = 3.20; 95% CI: 1.76–5.82; p < 0.001). Pg presence was linked to worse overall survival (HR ≈ 2.4; p < 0.01). TSA suggested that the accrued evidence for the primary incidence association is likely sufficient to reduce random errors; nevertheless, interpretability is constrained by the small number of observational studies and between-study differences in exposure and outcome ascertainment. Conclusions: Current evidence indicates that periodontitis and oral pathogens—particularly Fn and Pg—are significantly associated with CRC development and progression. These findings support the clinical relevance of the oral–gut axis and underscore oral health as a potentially modifiable factor in cancer prevention. Further large, well-designed prospective cohorts and mechanistic studies are warranted to strengthen causal inference. Full article

Background/Objectives: This study presents and explores the potential of Updated Bayesian Deduction (UBD) using colorectal cancer (CRC) detection and prioritisation as a case example. Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, and its prognosis strongly depends on early detection and timely treatment. In Chile, colonoscopy waiting lists for symptomatic patients in public hospitals can exceed one year, limiting access to early diagnosis and reducing survival rates. Traditional single-test screening strategies, such as a single faecal immunochemical test (FIT), often yield uncertain results, contributing to inefficiencies in resource allocation. Methods: We propose a deductive approach that integrates evidence from multiple sequential and independent FITs to dynamically update the posterior probability of CRC. A case study is analysed with this Updated Bayesian Deduction over a four-round FIT protocol to assess how this could improve risk stratification compared to standard symptoms-based screening. Results: Our mathematical model shows that over 85% of colonoscopies for symptomatic patients were not urgent. We then demonstrate that, if 4-FIT UBD were used to screen Chile’s Metropolitan Region population, only 96 out of 100,000 people would require an urgent colonoscopy to detect the 19.6 out of 100,000 individuals with CRC in this region. Many countries cannot afford a colonoscopy-based population screening, such as what is performed in Germany. Performing 4x FITs + a very small number of colonoscopies would be much more affordable and would get more countries to adopt general CRC screening. Conclusions: In countries with limited colonoscopy availability, such as Chile, where symptomatic patients can wait over a year for treatment in public hospitals, implementing a UBD-based strategy could drastically reduce costs and optimise the use of resources. This would improve access to colonoscopies for critical cases and ultimately enhance five-year survival rates. These findings highlight UBD as a promising approach for evidence-based precision medicine in CRC screening and prioritisation that is both explainable and adaptable. Full article

Background: Multiple primary lung cancer (MPLC) presents clinical challenges due to its biological complexity. While lobectomy remains standard, limited resection and localized ablation offer comparable efficacy. This systematic review evaluates the safety and efficacy of combining surgical and ablative therapies for MPLC. Methods: A comprehensive search of PubMed, Embase, and Web of Science (January 2000–2025) identified studies involving MPLC patients treated with both surgery and ablation, either concurrently or sequentially. Data on ablation efficacy, adverse events, and prognosis were extracted. A meta-analysis was performed when data pooling was appropriate. The methodological quality and risk of bias of the included studies were assessed using the MINORS and ROBINS-I tools. Publication bias was evaluated through funnel plots and Egger’s linear regression test. Furthermore, one case report on combination therapy was also included. Results: A total of nine studies met the inclusion criteria and were included in the final analysis. All reported a 100% technical success rate for ablation, efficacy rates exceeding 70%, and adverse event rates ranging from 5.0% to 26.7%. Due to significant heterogeneity among studies, a random-effects model was applied. The meta-analysis yielded a pooled ablation efficacy rate of 97.11% (95% CI: 85.81–100.00%) and a pooled adverse event rate of 14.23% (95% CI: 8.07–20.38%), indicating favorable safety and efficacy of the combined therapy. Conclusions: The integration of surgical and ablative therapies offers a safe and effective strategy for managing MPLC and supports a potential paradigm shift from single-modality treatment toward a more personalized, organ-preserving, and patient-centered approach. Full article

Adult patients affected by acute myeloid leukemia who fail to achieve remission after two cycles of intensive chemotherapy based on a combination of anthracyclines and cytarabine are considered chemorefractory and are unlikely to benefit from further induction attempts. Characterized by a poor prognosis, they may still benefit from allogeneic hematopoietic stem cell transplantation, even if long-term survival rarely exceeds 20–30%. Still, the use of sequential high-dose chemotherapy followed by reduced-intensity conditioning, with transplantation performed during aplasia, and the optimization of the alloreactivity of donor leukocytes against leukemia (i.e., the graft-versus-leukemia effect) may ameliorate these results. Optimization of alloreactivity against leukemic cells can be achieved by proper donor selection, by the early withdrawal of immunosuppressive therapy, by post-transplant administration of donor lymphocyte infusions as prophylaxis of leukemia relapse, and by several other maintenance and preemptive therapies. Far from being the final stage of consolidation therapy, allogeneic hematopoietic stem cell transplantation is now considered as the moment when a unique immunological platform can be established in these patients, to be used for additional post-transplant measures. In this study we will critically review the different pre- and post-transplant strategies used in clinical trials to improve long-term survival in adult patients transplanted with chemorefractory leukemia. Full article

Noninvasive liquid biopsy for monitoring circulating tumor cells offers valuable insights for predicting therapeutic responses. We developed TelomeScan^® (OBP-401), based on the detection of telomerase activity as a universal cancer cell marker and an indicator of the presence of viable circulating tumor cells (CTCs) for patients with advanced non-small cell lung cancer (NSCLC). This system evaluated CTC subtypes characterized by programmed death ligand 1 (PD-L1), an immune checkpoint molecule, and vimentin, an epithelial–mesenchymal transition (EMT) marker, using a multi-fluorescent color microscope reader. The prognostic value and therapeutic responses were predicted by dynamically monitoring CTC counts in 79 patients with advanced NSCLC. The sensitivity and specificity values of TelomeScan^® for PD-L1⁽⁺⁾ cells (≥1 cell) were 75% and 100%, respectively, indicating high diagnostic accuracy. PD-L1⁽⁺⁾ and EMT⁽⁺⁾ in CTCs were detected in 75% and 12% of patients, respectively. Detection of PD-L1⁽⁺⁾CTCs and PD-L1⁽⁺⁾EMT⁽⁺⁾ CTCs before treatment was associated with poor prognosis (p < 0.05). Monitoring of reducing and increasing PD-L1⁽⁺⁾ CTC counts in two sequential samples (baseline, cycle 2 treatment) correlated significantly with partial response (p = 0.032) and progressive disease (p = 0.023), respectively. Monitoring PD-L1⁽⁺⁾CTCs by TelomeScan^® will aid in anticipating responses or resistance to frontline treatments, optimizing precision medicine choices in patients with NSCLC. Full article

Background/Objectives: Sepsis is a high-mortality syndrome characterized by organ dysfunction resulting from a dysregulated host response to infection. This study aimed to evaluate the potential of growth differentiation factor 15 (GDF15), a stress-inducible cytokine, as a biomarker in patients diagnosed with urosepsis. Methods: A total of 13 patients diagnosed with urosepsis, based on an increase of ≥2 points in the Sequential Organ Failure Assessment (SOFA) score and positive urine culture, were included in the study. Daily blood samples were collected from patients for 10 days, and serum levels of GDF15, procalcitonin (PCT), and presepsin (P-SEP) were measured by ELISA. C-reactive protein (CRP), blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR), hemoglobin, and neutrophil, lymphocyte, and platelet counts were determined using autoanalyzers. Temporal changes were analyzed using the Friedman test, and correlations were analyzed using Spearman’s test. Results: GDF15 levels began to decrease from Day 3, with a significant decline observed from Day 7 compared to Day 1 (p < 0.001). Similar decreasing trends were observed in CRP and PCT levels, whereas presepsin levels did not exhibit significant changes. Significant positive correlations were identified between GDF15 and CRP (r = 0.65, p = 0.015), BUN (r = 0.57, p = 0.041), and creatinine (r = 0.62, p = 0.024), and a significant negative correlation was observed with eGFR (r = −0.62, p = 0.024). No significant correlation was found between GDF15 and presepsin (p > 0.05). Conclusions: GDF15 is a biomarker sensitive to the resolution phase of inflammation and organ dysfunction in sepsis, demonstrating significant temporal changes. It holds potential as an indicator for monitoring clinical progression and assessing prognosis. Full article

The focus of treatment of hepatocellular carcinoma (HCC) has shifted significantly from local therapy to systemic drug therapy. Recently, the efficacy of drug therapy for HCC has made rapid progress. We have transitioned from eras of sorafenib monotherapy and sequential therapy with multiple tyrosine kinase inhibitors that slightly improved patient prognoses, to an era where the introduction of immunotherapy combining atezolizumab and bevacizumab has achieved further improvements in patient prognosis. The availability of highly effective drugs has expanded the range of diseases treatable by drug therapy. Additionally, instead of initiating drug therapy at advanced stages, combining it with local therapies such as transarterial chemoembolization at an earlier stage with the aim of achieving a cure has become possible, improving treatment outcomes further. Currently, the number of regimens available for HCC, including combinations of multiple drugs and local therapies, has increased, leading to numerous clinical trials. Additionally, HCC cases that were previously unresectable are now resectable after drug therapy, necessitating the establishment of a resectability classification system. This review summarizes the current evidence for drug therapy for HCC and discusses future treatment strategies, treatment combinations, and prospects. Full article