Search Results (534)

Biomarkers that predict disease progression and treatment-free remission (TFR) would be of significant clinical value in chronic myeloid leukaemia (CML). We have previously shown that CIP2A levels at diagnosis can identify patients at increased risk of progression. One mechanism by which CIP2A acts is through upregulation of the anti-apoptotic gene BCL-XL. In this study, we evaluated BCL-XL mRNA expression as a diagnostic biomarker using samples from the SPIRIT2 and DESTINY clinical trials. In SPIRIT2, which compared imatinib and dasatinib as first-line therapies, high BCL-XL expression was associated with treatment failure, poor early molecular response, and lower rates of MR2 and MR3 achievement in patients treated with imatinib. In the DESTINY trial, which assessed treatment de-escalation and discontinuation, BCL-XL expression was significantly higher in patients who experienced molecular relapse compared to those achieving sustained TFR. Notably, increases in BCL-XL were detectable 6 to 8 months prior to molecular relapse, suggesting it may serve as an early biomarker of unsuccessful TFR. We now propose a clinical diagnostic toolkit combining CIP2A and BCL-XL biomarkers to stratify CML patients by the risk of disease progression and likelihood of achieving successful TFR. Full article

(1) Background: This follow-up retrospective analysis used electronic medical record (EMR) data from a health system to identify patients and medications prescribed in accordance with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. (2) Methods: This analysis included EMR data from a clinical research data warehouse encompassing 928,291 patients seen at an academic medical center between 2020 and 2024. The study evaluated 75 commercially available medications linked to 52 evidence-based CPIC pharmacogenomic (PGx) guidelines. (3) Results: Of the 928,291 patient encounters, 709,673 medication orders were recorded, with 416,621 patients (44.8%) prescribed at least 1 of the 75 CPIC-associated medications. This compares with 845,518 patients who had an encounter in 2015–2019 with 590,526 medication orders, and 335,849 (56.9%) patients had medication orders represented by CPIC-associated medications. One to three CPIC-associated medications accounted for 76.6% of patients in 2020–2024 compared to 75.6% in 2015–2019. (4) Conclusions: The findings demonstrate that the proportion of patients prescribed a CPIC-actionable medication remained just under half of those evaluated within a single institution’s EMR. About three-quarters of patients over the ten-year period had between one to three CPIC-associated medications identified, and the top five classes of medications remained the same in the two periods. This understanding of patient volume may help organizations as they begin to assess the implementation of PGx services. Full article

Background: Hypothyroidism is one of the most common endocrine conditions during pregnancy and has been associated with poor obstetric and perinatal outcomes. There is still a lack of data from Middle Eastern populations, despite its clinical significance. This study aimed to evaluate thyroid management patterns during pregnancy and examine the association between thyroid function control and maternal and perinatal outcomes in women with hypothyroidism at a tertiary care center in Qatar. Methods: A retrospective cohort study including 379 pregnant women with hypothyroidism diagnosed between January 2019 and November 2022 was conducted at Sidra Medicine in Doha, Qatar. Based on trimester-specific Thyroid-stimulating hormone (TSH )reference values, participants were categorized as having adequately or inadequately controlled thyroid function. Data on obstetrics, biochemistry, and demographics were taken from electronic medical records (EMR). Statistical analyses were performed using chi-square tests for categorical variables and t-tests for continuous variables, with a significance threshold of p < 0.05. Results: Participants had a mean Body Mass Index (BMI) of 30.33 ± 6.14 kg/m² and an average age of 32.65 ± 4.99 years; 54% of them were Qataris. Of the patients, 58.5% had positive thyroid antibodies and 55.7% had pre-gestational hypothyroidism. Women with pre-gestational hypothyroidism required significantly higher levothyroxine doses compared with those with gestational hypothyroidism (93.2 ± 47.5 mcg/day vs. 67.6 ± 30.1 mcg/day; p < 0.001). Treatment adjustment was demonstrated by the improvement in TSH normalization from 51.3% in the first trimester to 64.2% in the third trimester (p = 0.041). No significant associations were observed with pre-eclampsia, preterm delivery, hypertension, or placental abruption. However, women with normal third-trimester TSH had a higher prevalence of gestational diabetes mellitus (GDM) compared with those with elevated TSH (51.6% vs. 36.8%; p = 0.013). Conclusions: Appropriate trimester-specific monitoring and timely levothyroxine titration was associated with improved biochemical control without adverse maternal outcomes. Greater levothyroxine requirements in women with pre-gestational hypothyroidism emphasize the importance of early intervention. These findings highlight the potential benefit of structured thyroid monitoring and multidisciplinary care approaches in pregnancy and may help inform future regional clinical practice guidelines. Full article

Background: Measles and rubella remain major public health concerns in the Eastern Mediterranean Region (EMR), despite regional elimination goals. In 2023, the region experienced an increase in measles outbreaks. This study assessed outbreak detection and response challenges in either case definition or data analysis, in addition to gaps in laboratory and genotyping data integration to improve preparedness and response. Method: A retrospective epidemiological study was conducted using official World Health Organization (WHO) data on measles and rubella (MR) in EMR countries, from 1 January to 31 December 2023. Routine MR surveillance line list, genotyping data and supplemental immunization activity (SIA) reported by countries were used. Results: In 2023, 1206 suspected measles outbreaks were reported in 13 countries; 942 (78%) were confirmed. Rubella accounted for 158 confirmed outbreaks. Children under 5 years old comprised 76% of cases, with 62% zero dose. Timely detection was achieved in only 46% of outbreaks, with wide national variation. Genotype B3 predominated, but missing genotyping data limited verification. Six immunization campaigns occurred; however, outbreaks persisted due to high zero dose, limited targeting, and delayed responses. Conclusions: Persistent immunity gaps, under detection, inconsistent genotyping, and delayed response hindered MR control in EMR. Strengthening surveillance, integrating epidemiological and molecular data, expanding targeted supplementary immunization activities, and ensuring timely response are essential tasks. Standardized outbreak definitions, capacity building, and regular subnational analyses remain critical to regional elimination goals. Full article

The growing demand for functional foods reflects greater consumer awareness of diet–health links, with bioactive peptides receiving increasing attention for their health-promoting effects. In this study, bioactive peptides exhibiting antioxidant, dipeptidyl peptidase-IV (DPP-IV) inhibitory, and angiotensin-converting enzyme (ACE) inhibitory activities were produced from a jack bean (Canavalia ensiformis) protein isolate using a continuous proteolysis system with two enzymes. This study encompassed two major phases: isolating protein from jack beans and implementing a continuous enzymatic hydrolysis process. Key variables examined included the enzyme-to-substrate ratio ([E]/[S]), pH level, and residence time (τ). Optimal performance was achieved at [E]/[S] = 5%, pH = 7.5, and τ = 12 h, yielding a permeate with peptide content of 0.6143 mg SE/mL, along with notable antioxidant capacity and ACE inhibition of 0.0454 mg TEAC/mL and 92.18%, respectively. These results confirm that the jack bean protein isolate is a viable substrate for generating multifunctional bioactive peptides. This study provides a foundation for scalable and sustainable production of functional food ingredients from underutilized legumes using continuous bioprocessing technology. Industrial relevance: Integrating a stirred tank reactor with membrane separation provides a promising approach for continuous bioactive peptide production using a free-enzyme system, helping to streamline processing, reduces the demand for enzyme immobilization, and minimizes batch-to-batch variability. This study shows that continuous hydrolysis of jack bean protein isolate in EMR can enhance antioxidant activity and ACE inhibition of the hydrolysates. This approach offers a safer and more efficient route to support the commercialization of jack bean-based functional products. Full article

Purpose: Despite extensive evidence supporting synoptic reporting in adult surgical oncology, the pediatric surgical oncology evidence base remains sparse, institution-dependent, and implementation-limited, resulting in a critical translational gap. This systematic review evaluates the implementation and effectiveness of synoptic operative reports (SR) in improving documentation completeness in pediatric oncology surgery compared with traditional narrative reports (NR). Methods: Prospective and retrospective studies evaluating operative report completeness in pediatric oncology surgery were identified through a comprehensive search of PubMed, Scopus, and Web of Science. Of 1926 screened records, 11 articles underwent full-text review, and 4 studies met inclusion criteria. Results: The four included studies analyzed 341 operative reports (217 NRs and 124 SRs). Documentation completeness was the primary outcome. Across all evaluated intraoperative elements, synoptic reports were associated with approximately tenfold higher odds of complete documentation compared with narrative reports (pooled OR for NR vs. SR, 0.10; 95% CI, 0.07–0.14; p < 0.001). Conclusions: Synoptic reporting consistently improves the completeness of pediatric oncologic operative documentation compared with narrative formats; however, adoption in pediatric surgical oncology remains limited. Multicenter and implementation-focused research is needed to assess scalability, integration within electronic medical record (EMR) systems, and the impact of synoptic reporting on communication and clinical decision-making. Full article

Background: Pneumonia-associated sepsis constitutes a significant portion of all sepsis cases and is a leading cause of sepsis-related morbidity and mortality. The clinical burden is especially pronounced in general ward settings, where delayed recognition can hinder timely intervention. This underscores the necessity for advanced tools that facilitate early detection. Methods: This retrospective, single-center study assessed an AI-driven deep learning model designed to predict in-hospital sepsis up to four hours in advance. We analyzed 7715 pneumonia cases identified through chest radiography or CT. The model’s performance was evaluated using AUROC, sensitivity, specificity, and lead time to sepsis onset and was compared against established scoring systems: NEWS, MEWS, SOFA, and qSOFA. Sepsis was defined according to the CDC Adult Sepsis Event criteria in alignment with Sepsis-3 guidelines. Results: The AI model exhibited strong performance in the early detection of sepsis among pneumonia patients, achieving an AUROC of 0.870, with a sensitivity of 76.7% and specificity of 84.1%. It significantly surpassed conventional scoring systems: NEWS (0.697), MEWS (0.661), SOFA (0.649), and qSOFA (0.678). Importantly, the model identified sepsis a median of 183 min earlier than recognition based on the operational definition. This lead-time advantage was consistent in the pneumonia cohort, where 18.3% of patients developed sepsis. Conclusions: The AI model demonstrated strong predictive capabilities for pneumonia-associated sepsis, facilitating earlier clinical decision-making. Integrating this model into EMR systems could be an effective strategy to enhance sepsis outcomes in general ward settings. Further prospective studies are needed to validate its effectiveness in real-time clinical applications. Full article

With ongoing development in the process industries, the accumulation of industrial inorganic solid wastes (IISWs) has become increasingly significant. IISWs are characterized by large volume and toxicity and pose challenges in treatment and control. IISWs from chemical processes mainly include red mud (RM), zinc slag, lithium slag (LS), electrolytic manganese residue (EMR), phosphogypsum (PG), water treatment sludge (WTS), sewage sludge, blast furnace slag (BFS), steel slag (SS), coal fly ash (CFA), coal gasification slag (CGS), copper smelting slag (CSS), and lead smelting slag (LSS). Having been chemically processed, they exhibit complex compositions that pose challenges for further utilization. In this paper, we comprehensively review the preparation of adsorbents from IISWs as raw materials, the applications of IISW-derived adsorbents, and their adsorption mechanisms. The obtained adsorbents include modified IISWs, zeolites, porous ceramics, and composite and hybrid adsorbents. The adsorption mechanisms, such as van der Waals forces, electrostatic interactions, and π–π interactions, contribute to the rapid adsorption kinetics and high adsorption capacity observed in these adsorbents. Full article

The review aims at exploring models for case-base health programs across Africa that could best help Lesotho succeed in its efforts to establish a case-based surveillance (CBS) system for their HIV program. The review involves looking through several sources and databases including EBSCOHOST, Google Scholar, Science Direct and PubMed. The insights of suitable models were from the following Africa countries: South Africa, Kenya, Guinea, Tanzania, Ghana, Mozambique and Zambia. The study articles were published within the last 10 years, specifically from 2014 to 2024. This range was used as part of their inclusion criteria to ensure relevance of the articles. The studied models focused on infectious diseases such as measles, HIVand COVID-19. The key takeaway is that setting up electronic medical records systems (EMRs) is critical as a first step for any effective CBS. Using unique identifiers, establishing clear data governance policies and building strong infrastructure is a necessity in making CBS work. For a successful establishment of CBS, Lesotho should adopt these strategies that can be sustainable, improve disease tracking, response and ultimately health outcomes for Basotho. Full article

Machine learning (ML) algorithms may be effective at improving the HCV care cascade. One ML algorithm, developed using U.S. ambulatory electronic medical records (EMR), demonstrated the ability to identify people infected with HCV earlier than conventional testing strategies among those with indications for screening. We evaluated the potential cost-effectiveness of ML-enabled screening for the early identification of undiagnosed HCV among people in care in the U.S. An HCV natural history Markov model was developed to evaluate the cost-effectiveness of the ML algorithm-enabled screening compared to conventional testing over the training data period. Based on the training data, the ML algorithm identified patients on average 6.5 months earlier than conventional testing strategies. We compared the status quo to intervention scenarios using the ML algorithm at different recall levels (proportion of HCV patients identified, 5–100%). We identified the optimal algorithm recall level, which maximized health (measured in quality-adjusted life years, QALYs) while staying under a willingness-to-pay threshold of USD$100,000/QALY gained. ML-enabled screening was cost-effective (ICER < $100 k/QALY gained) in identifying undiagnosed HCV patients for recall levels up to 30%. The optimal recall level was 30% (Precision 0.27%), which resulted in a mean ICER of $94,022/QALY gained. ML-enabled screening for the early identification of undiagnosed HCV patients could be cost-effective in the U.S. Prospective evaluation of real-world effectiveness is warranted. Full article

Background: Unplanned 30-day hospital readmissions, a key healthcare quality metric, are common and costly. Prediction models built on structured data often perform modestly, and the added value of unstructured clinical notes remains unclear. Methods: This retrospective cohort study included 4135 general medicine admissions to a tertiary Australian hospital between July 2022 and June 2023. Structured predictors included demographics, comorbidities, frailty, prior healthcare utilisation, length-of-stay, inflammatory markers, socioeconomic indicators, and lifestyle factors. We developed deep learning models using structured data alone, unstructured text alone, and a combined multimodal architecture integrating both modalities. For benchmarking, multiple classical machine learning models trained on structured features were evaluated using identical data splits, including logistic regression, XGBoost, random forest, gradient boosting, extra trees, and HistGradient Boosting. Model performance was assessed on a hold-out test set using ROC-AUC, accuracy, precision, recall, and F1-score. Results: Unplanned readmissions occurred in 24.3% of admissions. Among classical machine learning models, logistic regression achieved the highest discrimination (ROC-AUC 0.64), with no substantial improvement observed from ensemble methods. Structured-only deep learning achieved ROC-AUC 0.62. Unstructured text-only and multimodal models achieved ROC-AUCs of 0.52 and 0.58, respectively. Although overall discrimination of the multimodal model was lower than structured-only performance, it demonstrated improved sensitivity and F1-score for identifying patients who were readmitted. Prior hospitalisations, emergency department visits, and comorbidity burden were the strongest predictors. Conclusions: Structured EMR variables remain the main drivers of 30-day readmission risk. More complex classical machine learning models did not outperform logistic regression, and incorporating unstructured clinical text provided only modest improvement in identifying high-risk patients without enhancing overall discrimination. Full article

Electronic Medical Records (EMRs) are mandatory in Indonesia following the Ministry of Health regulation, which raises significant challenges in data security and patient-centric access control. Current implementations rely on centralized healthcare systems or third-party vendors, creating risks of unauthorized access, data leakage, and uncertain data integrity. To address these issues, this study proposes DecMed, a decentralized EMR management framework built on IOTA Distributed Ledger Technology (DLT). DecMed integrates Capability-Based Access Control (CapBAC), Proxy Re-Encryption (PRE), and the InterPlanetary File System (IPFS) to enforce patient ownership of medical data. Patients actively grant or revoke access, define access duration, and selectively share data with healthcare personnel. The system is implemented using smart contracts in the Move programming language on the IOTA ledger, while encrypted clinical data is stored on IPFS. Evaluation through unit testing of various unauthorized access scenarios demonstrates that DecMed effectively enforces fine-grained access rules, preserves data confidentiality and integrity, and ensures compliance with national healthcare requirements. Full article

A robust analytical method based on Captiva EMR-Lipid solid-phase extraction and HPLC-MS/MS was developed and validated for the simultaneous determination of 19 aromatic amine antioxidants (AAs) and two p-phenylenediamine-derived quinones (PPD-Qs) in human plasma. The optimized protocol effectively removed phospholipid interferences from complex blood matrix, significantly mitigating ion suppression and improving the recovery of hydrophobic AAs compared to conventional liquid–liquid extraction. Method validation demonstrated good accuracy (spike recoveries: 73.0–96.8%), precision (RSD < 11%), and sensitivity with method detection limits ranging from 0.81 to 21 pg/mL. The method was successfully applied to plasma samples from 20 adults, in which 11 AAs were detected at total concentrations of 240–710 pg/mL. Diphenylamine derivatives, particularly bis(4-tert-butylphenyl)amine (DBDPA) and diphenylamine (DPA), were identified as the predominant compounds, contributing over 69% of the total AA burden. No PPDs or PPD-Qs were detected, which may be attributed to their biotransformation and urinary excretion, as well as the limited sample size. This study provides a comprehensive biomonitoring tool for assessing combined human exposure to multiple AAs and establishes a foundation for further investigation into their health implications. Full article

Background: Underwater endoscopic mucosal resection (UEMR) is a relatively new treatment method for sporadic non-ampullary duodenal epithelial tumors (SNADETs), and its usefulness has been reported for SNADETs ≤ 20 mm. However, its effectiveness and safety compared with conventional endoscopic mucosal resection (CEMR) remain controversial. This study aims to assess the treatment outcomes and evaluate the beneficial effects and safety of UEMR for SNADETs ≤ 20 mm. Methods: This is an open-label, multicenter collaborative, non-inferiority randomized controlled trial with two parallel groups conducted across 40 institutions in Japan. The study subjects will be patients with SNADETs ≤ 20 mm. A total of 320 patients will be randomized to either the CEMR or UEMR group in a 1:1 allocation ratio. The primary endpoint is the 1-year recurrence-free survival rate, defined as the number of cases with no recurrence of SNADET or death from any cause within one year of EMR. The secondary endpoints include the en bloc resection rate, histological complete resection rate, adverse events, technical success rate, total procedure time, resection time, mucosal closure time, complete mucosal closure rate, complete mucosal closure rate with standard clips, 1-year duodenum preservation survival rate, and device cost. Discussion: This multicenter, open-label, randomized controlled trial (RCT) with 320 subjects aims to determine whether the 1-year recurrence-free survival rate of underwater endoscopic resection is not inferior to that of conventional endoscopic mucosal resection for SNADETs ≤ 20 mm. If the efficacy and safety of UEMR are proven in this RCT, it is expected to be recognized as the standard treatment for SNADETs ≤ 20 mm. Owing to the absence of submucosal injection, UEMR is a simpler and more cost-effective technique compared to CEMR and is anticipated to become the primary method of EMR. Full article

Per-oral flexible endoscopy has expanded minimally invasive options for the management of gastric subepithelial tumors (G-SETs). This narrative review appraises conventional and advanced endoscopic resections alongside hybrid laparoscopic–endoscopic procedures, within a size- and layer-based clinical framework. Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) achieve high en bloc resection rates for small, intraluminal tumors arising from mucosa or submucosa. Traction strategies and dedicated traction devices may improve submucosal exposure, shorten procedure time, and reduce adverse events. Submucosal tunneling endoscopic resection (STER) has been developed to enucleate tumors originating from the muscularis propria while preserving mucosal integrity. However, tunnel creation and specimen retrieval become challenging for large tumors or for those located in the cardia or fundus. Endoscopic full-thickness resection (EFTR) enables controlled transmural excision of G-SETs arising from deeper wall layers. Exposed EFTR, combined with secure endoscopic closure, provides high en bloc and complete (R0) resection rates. Closure options range from through-the-scope clips—for small defects—to over-the-scope clips, endoloop-clip purse-string methods, reopenable-clip over-the-line techniques and endoscopic suturing systems—for larger defects. Non-exposed EFTR and device-assisted systems reduce the risk of peritoneal contamination, although complete resection rates are more variable. Hybrid approaches, including classical laparoscopic–endoscopic cooperative surgery (LECS) and non-exposure variants, combine endoscopic precision with the safety and closure capabilities of laparoscopic surgery, minimizing the amount of resected gastric wall. They are particularly suited to larger, awkwardly located or ulcerated G-SETs. Emerging traction platforms, flexible robotic systems, and AI-based tools may further broaden the role of per-oral flexible endoscopy for the treatment of G-SETs. However, evidence remains preliminary, and surgery continues to play a key role for large, extraluminal or anatomically prohibitive G-SETs. Full article