Search Results (139)

Assisted Reproductive Technology (ART), particularly In Vitro Fertilization (IVF), generates highly sensitive medical data classified as Protected Health Information (PHI) under international privacy and data protection laws. Ensuring the secure, transparent, and ethically governed management of this data is both essential and legally mandated. However, conventional Electronic Medical Record (EMR) systems often present significant challenges, including data-integrity risks, unauthorized access, and limited patient control—issues that become especially critical in contexts such as fertility preservation for cancer patients. EmbryoTrust introduces a blockchain-based framework designed to ensure the confidentiality, integrity, and availability of IVF-related information through a private, permissioned network integrated with role-based access control (RBAC). Smart contracts, implemented in Solidity on the Ethereum platform, verify spousal identities and enforce data immutability in compliance with religious legislation and ethical regulations. Off-chain data are stored in MongoDB for scalable, privacy-preserving management, while on-chain summaries provide tamper-evident traceability and verifiable auditability. The system was deployed and validated on the Ethereum Holešky testnet using Solidity 0.8.21 and Node.js 18.17, achieving an average transaction-confirmation time of 2.8 s, 99.9% uptime and a 95% user-satisfaction rate. Functional, integration, and usability testing confirmed secure and efficient data handling with minimal computational overhead. Comparative analysis demonstrated that the hybrid on-/off-chain architecture reduces latency and gas costs while maintaining automated compliance enforcement. The modular design enables adaptation to other jurisdictions by reconfiguring ethical and regulatory parameters within the smart-contract layer, ensuring flexibility for global deployment. Overall, the EmbryoTrust framework illustrates how blockchain logic can technically enforce medical and ethical rules in real time, providing a reproducible model for secure, culturally compliant, and privacy-preserving digital-health information management. Its alignment with Saudi Vision 2030 and the Wold Health Organization (WHO) Global Strategy on Digital Health 2020–2025 highlights its potential as a scalable solution for next-generation ART information systems. Full article

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with incidence steadily increasing due to cumulative ultraviolet (UV) exposure, impaired immune surveillance, and chronic tissue damage. While most cases are effectively managed with surgical excision, a subset progress to locally advanced or metastatic disease, associated with high recurrence rates, limited curative options, and poor prognosis. The introduction of immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis has significantly altered the management of advanced cSCC. Cemiplimab and pembrolizumab are now established systemic therapies, producing durable responses in a proportion of patients. These outcomes reflect the typically high tumor mutational burden and immunogenic microenvironment of cSCC. However, therapeutic decision-making remains particularly complex in several high-risk populations, including solid organ transplant recipients at risk of allograft rejection, patients with chronic dermatologic disorders or non-healing wounds that predispose to carcinogenesis, and individuals with rare hereditary syndromes such as recessive dystrophic epidermolysis bullosa. These so-called challenging populations are frequently excluded from pivotal trials, resulting in limited evidence regarding efficacy, safety, and optimal treatment strategies. This review summarizes current evidence on the management of advanced cSCC in high-risk and underserved patient groups, integrating trial data, real-world evidence, and contemporary guidelines. It also highlights key gaps in knowledge and outlines future directions, with particular focus on the interplay between host immune status, tumor biology, and therapeutic response. Full article

Background: The intersection between oncology and intensive care has shifted from predominantly end-of-life care to a therapeutic bridge that can preserve anticancer trajectories in carefully selected patients. Yet, criteria separating benefit from futility remain fragmented. Objective: This paper seeks to map contemporary evidence (2015–2025) on outcomes after Intensive Care Unit (ICU) admission in adults with cancer and to identify clinical constellations in which ICU-level care still changes prognosis. Methods: PRISMA-ScR scoping review (PCC framework). PubMed search (2015–2025), dual screening, standardized extraction; narrative/thematic synthesis across six clusters (hematologic, solid tumors, sepsis/non-COVID-19 infection, COVID-19/viral pneumonia, novel/targeted-therapy toxicities, end-of-life/aggressive ICU) were used. No meta-analysis given heterogeneity. Results: Seventy-three studies (>170,000 ICU admissions) were included, mostly cohort designs across 27 countries. ICU mortality ranged 8–72% (weighted mean ≈ 41%); hospital ≈ 38%; 90-day ≈ 46%; 1-year ≈ 62%. About one third of ICU survivors resumed systemic therapy. Benefit concentrated in early admissions, single-organ failure, controlled/remission disease, postoperative/elective monitoring, and reversible treatment-related toxicities (e.g., ICI pneumonitis, CAR-T CRS/ICANS). Futility clustered around ≥3 organ supports, RRT > 7 days, refractory/progressive disease, and ECOG ≥ 3. Sepsis outcomes averaged 45–55% ICU mortality but improved with rapid recognition and source control; COVID-19 mortality was particularly high in hematologic malignancies early in the pandemic, with subsequent declines post-vaccination. Conclusions: In modern oncologic practice, ICU care changes prognosis when the acute physiological insult is reversible and cancer control remains plausible; conversely, high organ-support burden and refractory disease define practical futility thresholds. These signals support time-limited ICU trials, earlier ICU involvement for sepsis/irAEs, and embedded palliative care to align intensity with goals. Full article

Prostate cancer is the most frequently diagnosed solid-organ malignancy in men worldwide. Metastatic castration-resistant prostate cancer represents a rapidly fatal, end-stage form of the disease for which current therapies remain palliative rather than curative. The advent of chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of refractory hematologic malignancies, and a growing number of studies are now exploring its potential in solid tumors. In this review, we first provide a concise overview of current immunotherapeutic strategies for prostate cancer, including checkpoint inhibitors, vaccine-based approaches, and bispecific antibodies. We then focus on the most recent and promising developments in CAR-T cell therapy for this malignancy. Specifically, we examine the key tumor-associated antigens targeted in prostate cancer-directed CAR-T cell therapy and summarize findings from preclinical research as well as ongoing and completed clinical trials. Finally, we discuss the main challenges that limit the efficacy of CAR-T therapy in prostate cancer, such as antigen heterogeneity, immunosuppressive tumor microenvironments, on-target/off-tumor toxicity, limited T-cell persistence, and inefficient trafficking to metastatic lesions, and outline potential strategies to overcome these barriers. Our aim is to define a translational roadmap for advancing CAR-T therapy toward clinical application in patients with metastatic castration-resistant prostate cancer. Full article

Vascular mimicry (VM) refers to the formation of vessel-like structures by tumor cells independent of endothelial cells. These VM channels connect to the host’s vascular network and are associated with aggressive tumors and poor patient prognosis. Most VM research has been conducted on melanoma, relying on patient-derived and mouse cell lines. In other solid tumors, VM studies rely on human cell lines, which have certain limitations for in vivo studies. Specifically, most in vivo VM research involving human cells uses subcutaneous mouse models that fail to recapitulate organ-specific tumor microenvironments. As the microenvironment is an essential driver of tumor vascularization, including VM, murine cell lines could facilitate VM investigations in syngeneic mouse models. Here, we present CT26 and KPC, well-characterized murine colorectal and pancreatic cancer cell lines, as cell models for VM investigations. Using in vitro cell-based assays, we demonstrate that CT26 and KPC undergo VM, a cell-intrinsic process that is enhanced by serum deprivation and exposure to hypoxia and is independent of tumor-secreted growth factors. Additionally, we demonstrate the importance of YAP/TAZ signaling in VM formation, as inhibition at non-cytotoxic concentrations attenuated VM formation. Remarkably, CA3, the most potent of the two inhibitors, significantly reduced cell proliferation in both cell lines at the IC₅₀ concentration. This reduction in cell proliferation was associated with the induction of apoptosis in CT26 cells and changes in the cell cycle in both CT26 and KPC cells. Finally, dual YAP/TAZ knockdown in both cell lines significantly abrogated VM formation, validating our initial findings using inhibitors. These results show that CT26 and KPC cells undergo VM, and given their extensive use in cancer research, can be used to investigate VM in vivo using syngeneic models. Full article

Background and Objectives: Advanced solid organ tumors, particularly breast, lung, and prostate cancers, frequently metastasize to bone, leading to debilitating skeletal-related events (SREs). Denosumab, a RANKL inhibitor, is crucial in preventing SREs. This study aimed to comparatively evaluate the efficacy and adverse effect profiles of denosumab in patients with bone metastases originating from these three common cancer types. Materials and Methods: This retrospective study included 146 patients treated with denosumab for bone metastases. Data on demographics, SREs before and during denosumab treatment, serum creatinine, calcium, and magnesium levels (at baseline, 3, and 6 months), other adverse effects, and survival were analyzed. Results: Before denosumab, SREs were present in 36.3% of patients (breast: 43.4%, prostate: 28%, lung: 33.8%). During denosumab treatment, SRE rates markedly decreased across all groups (breast: 9.4%, prostate: 16.0%, lung: 8.8%), with no significant intergroup difference in on-treatment SREs. Significant decreases in serum calcium levels were observed at 3 and 6 months post-denosumab initiation in breast (p < 0.0001) and lung cancer patients (p = 0.001). Mean creatinine levels significantly decreased in lung (p < 0.0001) and prostate (p = 0.020) cancer patients at 3 and 6 months. Overall survival significantly differed, with lung cancer patients having the shortest median survival (p < 0.005). Conclusions: Denosumab effectively reduces the incidence of SREs in patients with bone metastases from breast, lung, and prostate cancer. However, clinicians must diligently monitor for hypocalcemia, a notable adverse effect, particularly at 3 and 6 months after starting denosumab, with specific caution warranted in patients with lung cancer. Full article

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide, emphasizing the urgent need for early, non-invasive, and accessible diagnostic tools. This study aimed to evaluate the effectiveness of a microelectromechanical systems (MEMS)-based electronic nose (E-nose) in combination with gas chromatography–mass spectrometry (GC-MS) for CRC detection through sweat volatile organic compounds (VOCs). Methods: A total of 136 sweat samples were collected from 68 volunteer participants. Samples were processed using solid-phase microextraction (SPME) and analyzed by GC-MS, while a custom-designed E-nose system comprising 14 gas sensors captured real-time VOC profiles. Data were analyzed using multivariate statistical techniques, including PCA and PLS-DA, and classified with machine learning algorithms (LDA, LR, SVM, k-NN). Results: GC-MS analysis revealed statistically significant differences between CRC patients and healthy controls (COs). Cross-validation showed that the highest classification accuracy for GC-MS data was 81% with the k-NN classifier, whereas E-nose data achieved up to 97% accuracy using the LDA classifier. Conclusions: Sweat volatilome analysis, supported by advanced data processing and complementary use of E-nose technology and GC-MS, demonstrates strong potential as a reliable, non-invasive approach for early CRC detection. Full article

Background: A novel and highly effective strategy for tumor immunotherapy involves enhancing host immune responses against tumors through the blockade of checkpoint molecules. The most common toxicities associated with checkpoint blockade therapies include autoimmune damage to various organs. Purpose: This study aims to investigate hematological markers derived from complete blood counts (CBCs)—including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), derived neutrophil-to-lymphocyte ratio (dNLR), white blood cell-to-hemoglobin ratio (WHR), neutrophils, lymphocytes, platelets, hemoglobin, red blood cell (RBC) count, neutrophil-to-RBC ratio (NRR), and neutrophil-to-hemoglobin ratio (NHR)—as potential prognostic biomarkers for the early identification of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 immune checkpoint inhibitors. Materials and Methods: A prospective observational study was conducted on 44 patients with stage III-IV solid tumors treated with immune checkpoint (PD-1 or PD-1/CTLA-4) inhibitors. Thyroid function tests and CBC-derived biomarkers were collected at baseline, before immunotherapy. In the immunotherapy cohort, 15 of the 44 patients developed immune-related hypothyroidism, defined as overt autoimmune thyroiditis (TSH > 4.0, FT4 < 12, and anti-TPO antibodies > 30 IU/mL and/or anti-TG antibodies > 95 IU/mL) (Group 1). In comparison, 29 patients maintained normal thyroid function (Group 2). The control group comprised 14 age- and sex-matched healthy volunteers (Group 3). Statistical analyses were performed using analysis of variance (ANOVA) to compare blood parameters among the three groups (Group 1, Group 2, and Group 3) before treatment, with statistical significance set at a p-value < 0.05. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic power of the potential prognostic biomarkers areas. The area under the curve (AUC), sensitivity, and specificity were calculated for the 44 immunotherapy patients. Results: The PLR was significantly higher (262.25 ± 162.95), while WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes were lower (2.07 ± 0.66, 0.54 ± 0.19, 0.96 ± 0.28, 0.36 ± 0.14, 6.36 ± 2.07, 4.29 ± 1.55, and 1.23 ± 0.41, respectively) at baseline in Group 1 in comparison to Group 2. ROC curve analysis revealed that the areas under the curve (AUC) for WBCs, neutrophils, lymphocytes, WBCs-neutrophils, the PLR, the WHR, the NRR, and the NHR were 0.9, 0.87, 0.83, 0.85, 0.84, 0.92, 0.89, and 0.87, respectively. These values exceeded the threshold, indicating the high prognostic potential of each marker. Conclusions: Lower baseline levels of WBCs-neutrophils, the WHR, the NRR, the NHR, WBCs, neutrophils, and lymphocytes, along with a higher PLR, were associated with an increased risk of hypothyroidism in patients receiving PD-1 or PD-1/CTLA-4 inhibitors. These CBC-derived biomarkers represent simple, accessible, and potentially useful tools for predicting hypothyroidism in cancer patients undergoing immunotherapy. Further studies in bigger cohorts are needed to validate our findings. Full article

Hepatic mucormycosis is a rare but often fatal opportunistic fungal infection, primarily affecting immunocompromised patients. Herein, we report such a case from MD Anderson Cancer Center (Houston, TX, USA) and systematically review published cases in patients ≥ 19 years of age to better characterize clinical presentation, diagnostic challenges, and treatment outcomes of hepatic mucormycosis. Among the 40 identified cases (including ours), hematologic malignancies (55%) and solid organ transplantation (30%) were the most common underlying conditions. Fever (70%) and abdominal pain (63%) were the predominant symptoms. Imaging revealed multiple hepatic lesions in 72% of cases. Diagnosis was primarily based on histopathology (73%), whereas culture positivity was low (36%), underscoring the difficulty of pathogen isolation. Mucorales-active antifungal therapy was often delayed but eventually used in 85% of cases (all amphotericin B +/− Mucorales-active triazoles), while 45% underwent additional surgical intervention. Despite treatment, 1-year all-cause mortality remained high at 46%, with a trend towards lower mortality for those who underwent surgery compared to non-surgical management (35% vs. 55%, p = 0.334). These findings highlight the aggressive nature of hepatic mucormycosis and the importance of early recognition as well as the need for non-culture-based diagnostics and multimodal treatment approaches. Improved awareness and further research into optimized management strategies are crucial to improve the outcomes of this challenging infection. Full article

Liver transplantation (LT) has deeply transformed the treatment of end-stage liver disease and hepatocellular carcinoma, offering the most effective therapy for many liver conditions. However, LT carries inherent risks, including the development of cancers, which can arise from the transmission of neoplastic cells from the donor, the recurrence of pre-existing cancers, or as a long-term effect of the transplant, originating from the recipient’s own cells. The development of cancer in LT recipients is influenced by a variety of factors, such as age, gender, race, the underlying cause of liver disease, lifestyle factors (like alcohol use and smoking), and the use of immunosuppressive therapy. These combined factors increase the susceptibility of LT recipients to several types of cancer, including skin cancers, gastrointestinal malignancies, and lymphoproliferative disorders. While long-term survival after LT has significantly improved, there has been a notable increase in the incidence of de novo malignancies, which underscores the importance of diligent cancer screening and monitoring in transplant recipients, especially as they age. To manage this increased risk, various screening programs are recommended, including annual skin exams, colonoscopies for patients with primary sclerosing cholangitis (PSC) or inflammatory bowel disease (IBD), and lung cancer screening with low-dose CT for former smokers. When cancer is detected in LT recipients, reducing immunosuppression is a crucial strategy. Decreasing calcineurin inhibitors (CNIs) and integrating mTOR inhibitors (mTORis) provide promising avenues for balancing immunological control with oncological risk. Understanding these risk factors and adjusting immunosuppression appropriately is vital for improving cancer outcomes in LT recipients. Although evidence from LT-specific studies remains limited, insights from other solid organ transplant (SOT) settings, especially kidney transplants, offer valuable guidance in managing cancer risks in LT recipients. This narrative review focuses on the prevention and management of de novo and donor-transmitted malignancies. Full article

Background: Prospective studies evaluating the challenges of systematically assessing health-related quality of life in patients with cancer outside clinical trials are lacking. This study aimed to evaluate the quality of life of patients with cancer treated with immunotherapy such as checkpoint inhibitors and to determine the difficulties and limitations in achieving data collection from health-related quality of life questionnaires. Methods: We carried out a prospective observational study over 15 months in 30 patients with solid tumors undergoing checkpoint inhibitor therapy in an outpatient setting. We assessed health-related quality of life using the European Organization for Research and Treatment of Cancer QLQ-C30 quality of life questionnaire at treatment initiation, three months, and six months. We analyzed compliance rates, reported difficulties, and treatment-related toxicities. Results: Of the 30 patients, 26 completed the health-related quality of life standardized questionnaire at one month (86.6%), 24 at three months (80%), and 18 at six months (56.6%). Patients receiving checkpoint inhibitor monotherapy showed an improvement in global health status scores from 60 at baseline to 65 at three months and 70.8 at six months. These findings suggest that checkpoint inhibitor therapy delays symptom onset and positively impacts quality of life. Fatigue was the most frequently reported adverse effect, followed by pain, dyspnea, and gastrointestinal symptoms. Conclusions: Checkpoint inhibitor treatments may delay the onset of cancer-related symptoms, positively influencing patient-reported health-related quality of life (HRQoL) outcomes. However, this study highlights significant methodological challenges in collecting standardized HRQoL questionnaire data outside of clinical trials, including declining patient compliance over time. These findings underscore the need for adapted HRQoL assessment strategies tailored to the unique treatment trajectories of immunotherapy patients. Full article

Vasculogenic mimicry (VM) has recently been discovered as an alternative mechanism for nourishing cancer cells in vivo. During VM, tumor cells align and organize themselves into three-dimensional (3D) channel-like structures to transport nutrients and oxygen to the internal layers of tumors. This mechanism mainly occurs in aggressive solid tumors and has been associated with poor prognosis in oncologic patients. Long non-coding RNAs (lncRNAs) are essential regulators of protein-encoding genes involved in cancer development and progression. These single-stranded RNA molecules regulate critical cellular functions in cancer cells including cell proliferation, apoptosis, angiogenesis, VM, therapy response, migration, invasion, and metastasis. Recently, high-throughput RNA-sequencing technologies have identified thousands of lncRNAs, but only a small percentage of them have been functionally characterized in human cancers. The vast amount of data about its genomic expression in tumors can allow us to dissect their functions in cancer biology and make them suitable biomarkers for cancer diagnosis and prognosis. In this study, we reviewed the current knowledge about the role of lncRNAs in regulating VM in cancer. We also examined the molecular mechanisms of lncRNAs and highlight several commonalities in the cellular functions associated with VM between diverse cancer types. Future directions for research focused on deciphering their function in VM are delineated. Finally, the potential of selected lncRNAs as novel therapeutic targets in RNA-based molecular interventions is also discussed. Full article

Post-transplant lymphoproliferative disorder (PTLD) is the most common malignancy in adults who receive solid organ transplantation (SOT), apart from skin cancer. It is a serious and potentially fatal complication of chronic immunosuppression (ISI) in SOT recipients. This report describes a 20-year (2001–2021) clinicopathological experience with 59 PTLD patients at an urban center. The median time from transplant to PTLD was 8.5 years and the most common types of transplants were kidney (41%) and liver (31%). Epstein–Barr encoding region (EBER) was positive in 51% tumors, and 50% patients had Epstein–Barr virus (EBV) viremia at diagnosis. Overall survival (OS) at 1 year and 5 years was 78% and 64%, respectively. OS was significantly (p < 0.05) shorter in males (hazard ratio [HR] 3.7), certain organ transplants (lung HR 10.4; liver HR 3.9 relative to kidney), PTLD diagnosed within 12 months of transplant (HR 4.1), multi-organ involvement at diagnosis (HR 7.1), vitamin D deficiency at diagnosis (HR 4.5), and low serum albumin level at diagnosis (HR 3.6). Our study highlights the prognostic factors of PTLD and corroborates improved PTLD outcomes in the past 20 years. Full article

Background: mTOR-Is positively influence the occurrence and course of certain tumors after solid organ transplantation. mTOR-inhibitor (mTOR-I) treatment, either alone or in combination with Calcineurininhibitors (CNIs), significantly reduces the incidence of malignancies after organ transplantation. However, there is no information on which mTOR-I, Sirolimus (SIR) or Everolimus (ERL), has a stronger anti-tumoral effect. Methods: The current literature was searched for prospective randomized controlled trials in renal transplantation. There were 1.164 trials screened, of which 20 could be included (7465 patients). We performed a network meta-analysis to analyze the relative risk of different types of mTOR-I compared to CNI treatment on malignancies after transplantation. A minimum follow-up of 24 months was mandatory for inclusion. Results: Four different types of mTOR-I treatment were analyzed in network meta-analyses—SIR mono, ERL mono, SIR with CNI, and ERL with CNI. The average follow-up of all trials was 43.8 months. All four different mTOR-I regimes showed a significant reduced relative risk for malignancies compared to a regular CNI-treatment with the strongest effect under SIR in combination with a CNI (RR 0.23, CI 0.09–0.55, p = 0.001). This effect remained consistent for all tumor entities except non-melanoma skin cancer (RR 0.25, CI 0.07–0.90, p = 0.033). Conclusions: It is well known that an mTOR-I based treatment in transplant patients reduces the risk of tumor manifestation in comparison to CNI treatment. A combination of SIR and CNI seems to be the most potent mTOR-I therapy against malignancies. Full article

The profile of Volatile Organic Compounds (VOCs) may help prioritise at-risk groups for early cancer detection. Urine sampling has been shown to provide good disease accuracy whilst being patient acceptable compared to faecal analysis. Thus, in this study, urine samples were examined using an electronic nose with metal oxide gas sensors and a solid-phase microextraction sampling system. A calibration dataset (derived from a previous study) with CRC-positive patients and healthy controls was used to train a radial basis function neural network. However, a blinded analysis failed to detect CRC accurately, necessitating an enhanced data-processing strategy. This new approach categorised samples by significant bowel diseases, including CRC and high-risk polyps. Retraining the neural network showed an area under the ROC curve of 0.88 for distinguishing CRC versus non-significant bowel disease (without CRC, polyps or inflammation). These findings suggest that, with appropriate training sets, urine VOC analysis could be a rapid, low-cost method for early detection of precancerous colorectal polyps and CRC. Full article