Citations

Background: EUS-guided gastroenterostomy (EUS-GE) is an effective option for the management of gastric outlet obstruction (GOO). Due to the poor prognosis of patients undergoing it, data on its long-term adverse events (AE) is scarce. Herein, we describe a cohort of patients with gastro-entero-colic fistula (GECF) as a late AE of previously successful EUS-GE. Methods: Patients who developed a GECF after EUS-GE from 10 high-volume centers were analyzed. Information collected included demographic characteristics, indications, clinical and technical success rates, stent type and size, fistula characteristics, management, and outcomes. Results: Sixteen cases were identified. The mean interval from index EUS-GE to the diagnosis of GECF was 4 to 8 weeks. The most common cause of GOO was pancreatic adenocarcinoma (PDAC). The transverse colon was the most common site for the GECF (14 patients). A 20×10 mm lumen apposing metal stent (LAMS) was utilized in 10 patients. Endoscopic management with a variety of modalities was successful in 13 cases. Follow-up interval after endoscopic management of the fistula averaged 2 to 4 weeks. At the time of the manuscript elaboration, 10 patients had died, 5 were alive, and 1 was lost to follow-up. Conclusions: This is the first description of a cohort of patients with GECF after EUS-GE. The exact mechanisms leading to GECF in these cases are unknown. Possible explanations include inadvertent colon puncture during the index procedure and/or entrapment of mesocolon. More data is needed to further characterize this AE.

ABSTRACT Periprosthetic joint infection (PJI) is a serious complication of total joint arthroplasty (TJA), with Staphylococcus aureus being one of the most common causative organisms. Irrigation and debridement with component retention (IDCR) is often performed to manage PJI. Antimicrobial treatment that targets S. aureus biofilms on prosthesis surfaces and within bone may be especially helpful when retaining a prosthesis. Phages, viruses that specifically infect bacteria, are a potential therapeutic consideration. Using a biofilm time kill assay in bovine synovial fluid, bactericidal activity of vancomycin or phage K (32 µg/mL and 10 11 pfu/mL, respectively) as well as the combination of phage K (10 10 pfu/mL) and vancomycin (32 µg/mL) was observed against a methicillin‐resistant S. aureus (MRSA) strain. Using a murine PJI model, mice infected with MRSA underwent IDCR followed by phage administration into the joint space with or without systemically administered vancomycin. Mice receiving both phage and vancomycin had significant reductions in MRSA on the prosthesis surface compared to untreated or vancomycin‐treated mice. Phage K showed bactericidal activity in vitro and was active when locally delivered in combination with systemically administered vancomycin in a murine PJI model managed with IDCR.

ABSTRACT Despite remarkable interest in the biomarker potential of urinary extracellular vesicles (uEVs) and the identification of numerous promising candidates, their clinical translation still presents multiple challenges. The opportunities for successful translation are obvious, yet the main roadblocks on the way have hardly been systematically considered and more coordinated approaches are needed to overcome them. In the present review article, we have identified the most relevant roadblocks of clinical translation of urinary EV‐based biomarkers and discuss possible solutions to overcome them. These roadblocks are categorized as fundamental and technical but also related to development of novel biomarker assays and clinical acceptance. In addition, hurdles within the regulatory approval process are discussed. It is clear that various roadblocks to clinical translation of urinary EV biomarkers exist; however, they are addressable by promoting rigor and reproducibility as well as collaboration between basic and clinical scientists, clinicians, industry and regulatory bodies. Moreover, knowledge of obstacles for assay development and regulatory requirements should already be considered when developing a new biomarker to maximize the chance of successful translation. This review presents not only a status quo, but also a roadmap for the further development of the field.

ABSTRACT Background The circadian rhythm regulates gastrointestinal motility. In humans and preclinical models, such as rodents, whole gut transit (WGT) is slower during the rest phase compared to the active phase. Investigators typically study GI transit in rodents during the day, which is their rest phase, rather than during the night, which is their active phase. A circadian rhythm reversal in which mice are in a dark room during the working day (reverse light) allows studies on nocturnal animals during their active phase and has been previously shown to reduce WGT time. GI motility is often disrupted in individuals with disorders of gut–brain interaction (DGBI), which are female predominant. However, the effect of circadian rhythm on regional transit and sex dependence of the differences is not known, as most motility studies looking at circadian rhythm reversal are done in male mice. Methods We tested C57BL/6 wild‐type male and female mice in rest (12 h of light during the day) and active (reverse cycle for 2 weeks: 12 h of dark during the day) phases. We noted female estrous cycle by visual inspection. We performed carmine WGT by monitoring time‐lapse videos of pellet production. We performed fluorescence imaging of excised intestines 30 min after gavage to assess percent fluorescence for each GI region and then examined small intestinal transit (SIT) by measuring geometric center and leading edge. For colonic transit, we monitored bead expulsion time from distal colon to anus. Key Results Compared to rest phase, in the active phase, like male mice, female mice had (1) faster WGT, (2) increased frequency of pellet expulsion in the first 3 h of transit, (3) and greater total pellet production. Both male and female mice in their active phase exhibited (4) more contrast emptied from the stomach and they had (5) further leading edge of fluorescence and (6) geometric center, in SIT, and (7) faster colonic bead expulsion times. There were no significant sex differences in the active phase of WGT. In SIT, male mice had further leading edge in the rest phase than female mice, but this difference was not seen in the active phase, and in colonic transit, male mice in both the active and rest phases had faster bead expulsion than female mice. Conclusions Mice in the active phase have faster regional transit in small and large bowel than mice in the rest phase that collectively contributes to faster WGT times in the active phase of both male and female mice. These findings highlight the importance of circadian biology in sex‐dependent rodent GI transit.

Ketones, which are key biomarkers of fat oxidation, are relevant for metabolic health maintenance and disease development, making continuous monitoring essential. In this study, we introduce a novel colorimetric sensor designed for potential continuous acetone detection in biological fluids. The sensor features a polydimethylsiloxane (PDMS) shell that encapsulates a sensitive and specific liquid-core acetone-sensing probe. The microsphere sensors were characterized by evaluating their size, PDMS shell thickness, colorimetric response, and sensitivity under realistic conditions, including 100% relative humidity (RH) and CO2 interference. The microsphere size and sensor sensitivity can be controlled by modifying the fabrication parameters. Critically, the sensor showed high selectivity for acetone detection, with negligible interference from CO2 concentrations up to 4%. In addition, the sensor displayed good reproducibility (CV < 5%) and stability under realistic storage conditions (over two weeks at 4 °C). Finally, the accuracy of the microsphere sensor was validated against a gold standard gas chromatography-mass spectrometry (GC-MS) method using simulated and real breath samples from healthy individuals and type 1 diabetes patients. The correlation between the microsphere sensor and GC-MS produced a linear fit with a slope of 0.948 and an adjusted R-squared value of 0.954. Therefore, the liquid-core microsphere-based sensor is a promising platform for acetone body fluid analysis.

The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms. Untreated brain metastases on standard anatomic MRI sequences (T1, T2, FLAIR, T1PG) from eight contributed international datasets were annotated in stepwise method: published UNET algorithms, student, neuroradiologist, final approver neuroradiologist. Segmentations were ranked based on lesion-wise Dice and Hausdorff distance (HD95) scores. False positives (FP) and false negatives (FN) were rigorously penalized, receiving a score of 0 for Dice and a fixed penalty of 374 for HD95. The mean scores for the teams were calculated. Eight datasets comprising 1303 studies were annotated, with 402 studies (3076 lesions) released on Synapse as publicly available datasets to challenge competitors. Additionally, 31 studies (139 lesions) were held out for validation, and 59 studies (218 lesions) were used for testing. Segmentation accuracy was measured as rank across subjects, with the winning team achieving a LesionWise mean score of 7.9. The Dice score for the winning team was 0.65 ± 0.25. Common errors among the leading teams included false negatives for small lesions and misregistration of masks in space. The Dice scores and lesion detection rates of all algorithms diminished with decreasing tumor size, particularly for tumors smaller than 100 mm3. In conclusion, algorithms for BM segmentation require further refinement to balance high sensitivity in lesion detection with the minimization of false positives and negatives. The BraTS-METS 2023 challenge successfully curated well- annotated, diverse datasets and identified common errors, facilitating the translation of BM segmentation across varied environments and providing the tools for future development of personalized volumetric reports to patients undergoing BM treatment.

Abstract INTRODUCTION Neurofilament light chain (NfL) quantification aids in diagnosing and predicting neurological disorders, but clinical and laboratory practices vary across centers. Differences in result interpretation and reporting further challenge test commutability. This study aimed to review the global analytical and post‐analytical methods used for NfL measurement in routine clinical practice across different contexts. METHODS We established an international working group (WG) and distributed a survey to its members to gather information on context of use (COU), (pre) analytical methods, cutoff usage, as well as the interpretation and reporting of NfL measurements. RESULTS Among the centers, 63% measured NfL in cerebrospinal fluid (CSF), 87% in blood, and 53% in both. COU was widespread, with 50% defining pathological cutoffs based on publications and 42% considering age. Reporting was primarily done through numeric results (95%). DISCUSSION Harmonizing cutoffs, reporting, and interpretation across various clinical contexts will facilitate the incorporation of this biomarker into routine clinical practice. Highlights Unique international overview of current analytical and post‐analytical methods for neurofilament light chain (NfL) measurement in routine clinical practice. Tailored sheets for each neurological application. Strategies to harmonize cutoffs, reporting, and interpretation of NfL's measurement.

Background: Over 2.3 million liposuctions are performed annually with a complication rate of approximately 5%, including a death rate of 1 in 5000 because of blood loss. Artificial intelligence models offer potential for improving blood loss prediction and management in these procedures, analyzing extensive data to identify risk factors and accurately estimate blood loss. Methods: Data from 721 large-volume liposuction patients at 2 centers in Bogotá, Colombia, and Loja, Ecuador, between 2019 and 2023 were evaluated. Both centers followed identical perioperative protocols. The data set was split into training (621 patients) and testing (100 patients) sets. A supervised machine learning model was trained to predict blood loss. Model predictions were compared with clinical data using statistical validation metrics. Results: Most patients were women (79.2%), with median values of age of 37 years; weight, 65 kg; height, 165 cm; body mass index, 24.34 kg/m²; volemia, 3924.41 mL; infiltrated volume, 5800 mL; and aspirated volume, 3900 mL. Previous liposuction was noted in 32%. No significant differences were found between training and testing cohorts. The model achieved a mean absolute error of 22.09 mL, root mean square error of 34.13 mL, and an R ² value of 0.974, indicating high predictive accuracy and excellent model fit. Conclusions: The authors’ study has developed and validated an accurate artificial intelligence–based model to predict blood loss in large-volume liposuction, showing 94.1% accuracy. The authors’ model enhances preoperative planning and intraoperative management, potentially reducing complications and improving outcomes.

Inherited platelet disorders (IPDs) are a group of rare conditions affecting platelet number, function, or both. Clinical manifestations vary widely, from asymptomatic cases to patients with severe bleeding, syndromic features, or early-onset blood cancers. Some are diagnosed due to family history. Early and accurate diagnosis—through both clinical and molecular evaluation—is essential for effective patient management and to avoid inappropriate treatments due to misdiagnosis. Genetic confirmation aids in prognosis, follow-up planning, family screening, genetic counseling, and donor selection for stem cell transplantation if required. However, diagnosing IPD is still challenging due to the disorders’ complexity and the limitations of current lab tests. This review outlines the diagnostic process for IPD and provides evidence-based, practical recommendations informed by scientific literature and clinical experience.