Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Machine learning-based response assessment in patients with rectal cancer after neoadjuvant chemoradiotherapy: radiomics analysis for assessing tumor regression grade using T2-weighted magnetic resonance images.

PURPOSE: This study aimed to assess tumor regression grade (TRG) in patients with rectal cancer after neoadjuvant chemoradiotherapy (NCRT) through a machine learning-based radiomics analysis using baseline T2-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: In total, 148 patients with locally advanced rectal cancer(T2-4 or N+) who underwent MR imaging at baseline and after chemoradiotherapy between January 2010 and May 2021 were included. A region of interest for each tumor mass was drawn by a radiologist on oblique axial T2-weighted images, and main features were selected using principal component analysis after dimension reduction among 116 radiomics and three clinical features. Among eight learning models that were used for prediction model development, the model showing best performance was selected. Treatment responses were classified as either good or poor based on the MR-assessed TRG (mrTRG) and pathologic TRG (pTRG). The model performance was assessed using the area under the receiver operating curve (AUROC) to classify the response group. RESULTS: Approximately 49% of the patients were in the good response (GR) group based on mrTRG (73/148) and 26.9% based on pTRG (28/104). The AUCs of clinical data, radiomics models, and combined radiomics with clinical data model for predicting mrTRG were 0.80 (95% confidence interval [CI] 0.73, 0.87), 0.74 (95% CI 0.66, 0.81), and 0.75(95% CI 0.68, 0.82), and those for predicting pTRG was 0.62 (95% CI 0.52, 0.71), 0.74 (95% CI 0.65, 0.82), and 0.79 (95% CI 0.71, 0.87). CONCLUSION: Radiomics combined with clinical data model using baseline T2-weighted MR images demonstrated feasible diagnostic performance in predicting both MR-assessed and pathologic treatment response in patients with rectal cancer after NCRT.

Coccygodynia in a Long-Term Cancer Survivor Diagnosed with Metastatic Cancer: A Case Report.

Background and Objectives: Rectal cancer is considered cured if no recurrence is found during the 5-year follow-up period after treatment. After this period, patients often believe that the cancer is completely eradicated. However, in modern society, where lifespans have become longer, it is important to recognize that metastatic cancer may occur long after the initial treatment has concluded. This highlights the necessity of continued vigilance and the long-term follow-up of cancer survivors. Case report: We present a case of metastatic cancer of the coccyx in an 87-year-old female patient. This patient had undergone successful surgery and treatment for rectal cancer 10 years prior. She was considered cured after the standard 5-year follow-up period as she showed no signs of recurrence. The patient presented with simple coccygeal pain as the main complaint, without any other accompanying symptoms such as weight loss, fever, or changes in bowel habits, typically associated with cancer recurrence. During the clinical evaluation, irregularities in the bone cortex were detected while performing a nerve block using ultrasound. Given these findings, further diagnostic evaluations were performed. Advanced imaging techniques including MRI and CT scans led to a diagnosis of coccygeal metastasis. Conclusions: While the 5-year mark post-treatment is a significant milestone for rectal cancer patients, it does not guarantee the absolute eradication of the disease. Long-term monitoring and a thorough evaluation of new symptoms are essential for the early detection and management of late metastatic recurrences. This approach ensures that patients receive timely and appropriate care, potentially improving outcomes and quality of life.

Assessing Active Bowel Inflammation in Crohn's Disease Using Intestinal Ultrasound: Correlation With Fecal Calprotectin.

AIM: To analyze the correlation between intestinal ultrasound (IUS) and serum and fecal biomarkers, and the characteristics of small bowel disease, for the assessment of active bowel inflammation. METHODS: Patients with Crohn's disease (CD) who underwent an initial IUS examination between July 2018 and November 2022 at our institution were included retrospectively. We divided small and large bowels into seven segments, and recorded the presence of active inflammation according to following criteria: bowel wall thickness ≥ mm with ≥1 of feature of active disease on IUS. The correlations between IUS-assessed activity and serum C-reactive protein (CRP, mg/dL) and fecal calprotectin (FC, µg/g) levels were analyzed. RESULTS: A total of 127 patients were included (mean age: 32.42 ± 12.07, M:F = 90:37, median disease duration 6 years [0-35]). Of them, 78 showed active bowel inflammation (61.4%), with inflammation distal to the terminal ileum being the most common disease location (n = 61, 78.2%). FC and serum CRP levels were significantly correlated with the number of segments with active inflammation (rho = 0.58, 0.48), number of segments with complications (r = 0.35, 0.31), and US activity score (r = 0.62, 0.54). With FC cutoff values of 100 and 150 µg/g, the concordance rates for patients with active small bowel disease were 78.7% (26/33) and 72.7% (24/33), respectively, which were better than those for other disease locations. CONCLUSIONS: Disease activity determined by IUS was significantly correlated with the biomarkers, with a better concordance rate in patients with active small bowel disease than in those with other disease locations with FC cut-off values of 100 and 150 µg/g.

Alignment-tolerant single-shot digital holographic microscopy based on computer-controlled telecentricity.

An alignment-tolerant telecentric digital holographic microscopy (AT-T-DHM) system based on computer-controlled telecentricity is proposed. It consists of a three-step process-optical recording, computational compensation, and retrieving processes. With a tube-lens-based two-beam interferometer, phase information of the object is recorded on the hologram, where another optical quadratic phase error (O-QPE) due to the misalignment of the tube lens happens to be added. In the computational compensation process, this phase error can be estimated, by which the O-QPE is balanced out from the recorded hologram. Then, only the phase information of the object can be retrieved from the O-QPE-compensated hologram. This computational compensation process makes the proposed system virtually operate in a telecentric imaging mode, which enables implementing a practical AT-T-DHM. Wave-optical analysis and experiments with a test object confirm the feasibility of the proposed system.

Closha: bioinformatics workflow system for the analysis of massive sequencing data.

BACKGROUND: While next-generation sequencing (NGS) costs have fallen in recent years, the cost and complexity of computation remain substantial obstacles to the use of NGS in bio-medical care and genomic research. The rapidly increasing amounts of data available from the new high-throughput methods have made data processing infeasible without automated pipelines. The integration of data and analytic resources into workflow systems provides a solution to the problem by simplifying the task of data analysis. RESULTS: To address this challenge, we developed a cloud-based workflow management system, Closha, to provide fast and cost-effective analysis of massive genomic data. We implemented complex workflows making optimal use of high-performance computing clusters. Closha allows users to create multi-step analyses using drag and drop functionality and to modify the parameters of pipeline tools. Users can also import the Galaxy pipelines into Closha. Closha is a hybrid system that enables users to use both analysis programs providing traditional tools and MapReduce-based big data analysis programs simultaneously in a single pipeline. Thus, the execution of analytics algorithms can be parallelized, speeding up the whole process. We also developed a high-speed data transmission solution, KoDS, to transmit a large amount of data at a fast rate. KoDS has a file transfer speed of up to 10 times that of normal FTP and HTTP. The computer hardware for Closha is 660 CPU cores and 800 TB of disk storage, enabling 500 jobs to run at the same time. CONCLUSIONS: Closha is a scalable, cost-effective, and publicly available web service for large-scale genomic data analysis. Closha supports the reliable and highly scalable execution of sequencing analysis workflows in a fully automated manner. Closha provides a user-friendly interface to all genomic scientists to try to derive accurate results from NGS platform data. The Closha cloud server is freely available for use from http://closha.kobic.re.kr/ .

Single-shot digital holographic microscopy with a modified lateral-shearing interferometer based on computational telecentricity.

Single-shot digital holographic microscopy (SS-DHM) with a modified lateral-shearing interferometer (MLSI) based on computational telecentricity is proposed. The proposed system is composed of three-step processes such as optical recording, digital compensation and numerical reconstruction processes. In the 1st step, the object beam is optically recorded with the MLSI, where a tube lens is set to be located at the slightly shorter distance than its focal length from the objective lens. Then, another phase factor due to the deviated locating of the tube lens from its focal length is additionally generated, which is called an additional quadratic phase factor (AQPF). However, in the 2nd step, this AQPF can be balanced out with the computer-generated version of the AQPF. In the 3rd step, the three-dimensional (3-D) object can be finally reconstructed from this AQPF-compensated hologram. Thus, by combined use of the optical recording and digital compensation processes of the AQPF, the proposed system can be made virtually operate in a so-called computational telecentricity, which enables us to implement a MLSI-based SS-DHM system. Wave-optical analysis and successful experiments with actual 3-D objects confirm the feasibility of the proposed system in the practical application fields.

Ultraviolet photodetector using pn junction formed by transferrable hollow n-TiO2 nano-spheres monolayer.

We report an ultraviolet (UV) photodetector with a universally transferable monolayer film with ordered hollow TiO2 spheres on p-GaN. After forming a TiO2 monolayer film by unidirectional rubbing of hollow TiO2 spheres on a polydimethylsiloxane (PDMS) supporting plate, we used a 5% polyvinyl alcohol (PVA) aqueous solution to transfer the film onto the target substrate. The PVA/TiO2 monolayer film was detached from the PDMS film and transferred to the p-GaN/Al2O3 substrate. To investigate the effects of crystallized phases of the TiO2 hollow spheres, anatase and rutile TiO2 sphere monolayers prepared by combining template synthesis and thermal treatment. The responsiveness of the UV photodetectors using anatase and rutile hollow n-TiO2 monolayer/p-GaN was 0.203 A/W at 312 nm and 0.093 A/W at 327 nm, respectively.

An Algorithm for Management After Transjugular Intrahepatic Portosystemic Shunt Placement According to Clinical Manifestations.

We propose an algorithm for management after transjugular intrahepatic portosystemic shunt (TIPS) placement according to clinical manifestations. For patients with an initial good clinical response, surveillance Doppler ultrasound is recommended to detect stenosis or occlusion. A TIPS revision can be performed using basic or advanced techniques to treat stenosis or occlusion. In patients with an initial poor clinical response, a TIPS venogram with pressure measurements should be performed to assess shunt patency. The creation of a parallel TIPS may also be required if the patient is symptomatic and the portal pressure remains high after TIPS revision. Additional procedures may also be necessary, such as peritoneovenous shunt (Denver shunt) placement for refractory ascites, tunneled pleural catheter for hepatic hydrothorax, and balloon-occluded retrograde transvenous obliteration procedure for gastric variceal bleeding. A TIPS reduction procedure can also be performed in patients with uncontrolled hepatic encephalopathy or hepatic failure.

Slim-structured electro-floating display system based on the polarization-controlled optical path.

A new slim-type electro-floating display system based on the polarization-controlled optical path is proposed. In the proposed system, the optical path between the input plane and Fresnel lens can be made recursive by repetitive transmission and reflection of the input beam by employing a new polarization-based optical path controller (P-OPC), which is composed of two quaterwave plates, a half mirror and a reflective polarizer. Based on this P-OPC, the absolute optical path between the input plane and Fresnel lens, virtually representing the physical depth of the display system, can be reduced down to one third of its original path, which results in the same rate of decrease in the volume size of the display system. The operational principle of the proposed system is analyzed with the Jones matrix. In addition, to confirm the feasibility of the proposed system, experiments with test prototypes are carried out, and the results are comparatively discussed with those of the conventional system.

Sonography of Abdominal Wall Masses and Masslike Lesions: Correlation With Computed Tomography and Magnetic Resonance Imaging.

Sonography is usually regarded as a first-line imaging modality for masses and masslike lesions in the abdominal wall. A dynamic study focusing on a painful area or palpable mass and the possibility of ultrasound-guided aspiration or biopsy are the major advantages of sonography. On the other hand, cross-sectional imaging clearly shows anatomy of the abdominal wall; thereby, it is valuable for diagnosing and evaluating the extent of diseases. Cross-sectional imaging can help differentiate neoplastic lesions from non-neoplastic lesions. This pictorial essay focuses on sonographic findings of abdominal wall lesions compared with computed tomographic and magnetic resonance imaging findings.

Sonography of Gastrointestinal Tract Diseases: Correlation With Computed Tomographic Findings and Endoscopy.

Sonographic evaluation of the gastrointestinal (GI) tract may be difficult because of overlying intraluminal bowel gas and gas-related artifacts. However, in the absence of these factors and with the development of high-resolution scanners and the technical experience of radiologists, sonography can become a powerful tool for GI tract assessment. This pictorial essay focuses on sonographic findings of GI tract lesions compared with endoscopic, computed tomographic, and magnetic resonance imaging findings. Neoplastic and non-neoplastic diseases and postoperative complications are illustrated, and the distinctive sonographic characteristics of these entities are highlighted.

Distribution of Epididymal Involvement in Mumps Epididymo-orchitis.

OBJECTIVES: To evaluate characteristic sonographic findings for mumps orchitis with epididymal involvement. METHODS: This study included 18 patients (aged 12-18 years) with mumps orchitis. We assessed the volume, echogenicity, and vascularity of the testes and the transverse diameter, echogenicity, and vascularity of the epididymal head, body, and tail. We classified 4 types of epididymal involvement: 1A, focal swelling of the epididymal head with hypervascularity only on the swollen head; 1B, focal swelling of the epididymal head with hypervascularity on the entire epididymis; 1C, diffuse swelling of the entire epididymis with hypervascularity; and 2, no epididymal involvement. The Student t test was used to evaluate the significance of the size of each part of the epididymis and the epididymal head-to-tail diameter ratio. RESULTS: Orchitis was unilateral in 13 patients and bilateral in 5. Of 23 affected hemiscrotums, 7 (30.4%) were type 1A, 4 (17.4%) type 1B, 2 (8.7%) type 1C, and 10 (43.5%) type 2. In 11 patients with unilateral epididymal involvement, the mean diameters ± SDs of the epididymal heads on the affected and contralateral sides were 1.11 ± 0.19 (range, 0.7-1.7) and 0.65 ± 0.14 (0.3-0.9) cm (significantly different, P <.001). The diameters of the epididymal tails on the affected and contralateral sides were 0.51 ± 0.41 (0.2-0.8) and 0.46 ± 0.21 (0.3-0.6) cm (not statistically different, P = .106). The mean head-to-tail ratios on the affected and contralateral sides were 2.28 ± 0.49 (1.29-3.00) and 1.41 ± 0.22 (1.00-1.75; significantly different, P < .001). In all types 1A and 1B, the ratio was higher than 2.00; in 22 of 23 unaffected epididymides, the ratio was lower than 2.00. CONCLUSIONS: Focal swelling of epididymal heads was a characteristic sonographic finding of mumps epididymo-orchitis, and a head-to-tail ratio higher than 2.00 can be a useful diagnostic finding.

Gastrointestinal tract perforation: evaluation of MDCT according to perforation site and elapsed time.

OBJECTIVES: To evaluate multidetector computed tomography (MDCT) for the prediction of perforation site according to each gastrointestinal (GI) tract site and elapsed time. METHODS: One hundred and sixty-eight patients who underwent MDCT before laparotomy for GI tract perforation were enrolled and allocated to an early or late lapse group based on an elapsed time of 7 h. Two reviewers independently evaluated the perforation site and assessed the following CT findings: free air location, mottled extraluminal air bubbles, focal bowel wall discontinuity, segmental bowel wall thickening, perivisceral fat stranding and localised fluid collection. RESULTS: The overall diagnostic accuracy was 91.07 % and 91.67 % for reviewers 1 and 2, respectively, with excellent agreement (kappa 0.86). Accuracies (98.97 % and 97.94 %) and agreements (kappa 0.894) for stomach and duodenum perforation were higher than for other perforation sites. Strong predictors of perforation at each site were: focal bowel wall discontinuity for stomach, duodenal bulb and left colon, mottled extraluminal air bubbles for retroperitoneal duodenum and right colon, and segmental bowel wall thickening for small bowel. The diagnostic accuracy was not different between the early- and late-lapse groups. CONCLUSIONS: MDCT can accurately predict upper GI tract perforation with high reliability. Elapsed time did not affect the accuracy of perforation site prediction. KEY POINTS: Perforation of the stomach and duodenum can be accurately predicted with MDCT. Knowledge of CT findings predicting perforation site can improve diagnostic accuracy. Elapsed time does not significantly affect accuracy in predicting perforation sites.

Diagnostic effectiveness of dynamic colpocystoproctography in women planning for combined surgery with urinary incontinence and pelvic organ prolapse.

OBJECTIVE: To evaluate the advantage of performing the dynamic cystoproctography (DCP) in patients planning for combined surgery due to urinary incontinence and pelvic organ prolapse (POP). MATERIALS AND METHODS: We performed DCP on a total of 113 consecutive women with POP and compared the findings of the physical examination with POP quantification against those of DCP including squeezing, straining and evacuation phases, and analyzed the changes to the rates of surgical planning. For statistical analysis, sensitivity, specificity, and positive predictive value of each test were performed. RESULTS: DCP identified an additional 10 cases of cystocele, 32 cases of rectocele, 2 cases of enterocele, 4 cases of sigmoidocele, and 8 cases of rectal intussusception compared to those cases who were only included for a physical examination. The initial surgical plan was changed in a total of 24 cases (22.1%). The prevalence of bowel symptoms in the group in which the surgical plan changed was higher than in the group with no changes to the surgical plan (p = 0.023). CONCLUSIONS: DCP may be a more sensitive test for diagnosing POP compared to physical examination alone, and it is useful to patients with bowel symptoms by making surgical planning for combined surgery with stress urinary incontinence and POP.

[Postoperative Imaging Findings of Colorectal Surgery: A Pictorial Essay]. / 대장 직장 ìˆ˜ìˆ ì˜ ìˆ˜ìˆ í›„ 영상 소견들: 임상화보.

Postoperative colorectal imaging studies play an important role in the detection of surgical complications and disease recurrence. In this pictorial essay, we briefly describe methods of surgery, imaging findings of their early and late complications, and postsurgical recurrence of cancer and inflammatory bowel disease.

Synergistic anticancer immunity in metastatic triple-negative breast cancer through an in situ amplifying Peptide-Drug Conjugate.

Despite significant progress in combining cancer immunotherapy with chemotherapy to treat triple negative breast cancer (TNBC), challenges persist due to target depletion and tumor heterogeneity, especially in metastasis. Chemotherapy lacks precise targeting abilities, and targeted therapy is inadequate in addressing the diverse heterogeneity of tumors. To address these challenges, we introduce RGDEVD-DOX as a tumor-specific immunogenic agent, namely TPD1, which targets integrin αvß3 and gets continuously activated by apoptosis. TPD1 facilitates the caspase-3-mediated in situ amplification that results in tumor-specific accumulation of doxorubicin. This local concentration of doxorubicin induces immunogenic cell death and promotes the recruitment of immune cells to the tumor site. Notably, the tumor-targeting capabilities of TPD1 help bypass the systemic immunotoxicity of doxorubicin. Consequently, this alters the tumor microenvironment, converting it into a 'hot' tumor that is more susceptible to immune checkpoint inhibition. We demonstrated the anti-metastatic and anti-cancer efficacy of this treatment using various xenograft and metastatic models. This study underscores the high potential of caspase-3 cleavable peptide-drug conjugates to be used in conjunction with anti-cancer immunotherapies.

Net global warming potential index rather than soil carbon stock change could provide better understanding of the carbon balance in soil systems.

This study was conducted to determine the soil organic carbon (SOC) stock change factor for green manure crops that was developed by the Intergovernmental Panel on Climate Change (IPCC) Tier 2 method and compare this with the net global warming potential (GWP) index that is used to evaluate the contribution of green manuring to global warming. Four treatments were barley (Hordeum vulgare L.; B), hairy vetch (Vicia villosa R.; HV), a barley/hairy vetch mixture (BHV) and a conventional treatment (C). The aboveground biomass of green manure crops was incorporated into the soil on 25 May 2018, 26 April 2019, 29 April 2020, 30 April 2021 and 2 May 2022. Maize (Zea mays L.) was transplanted as the subsequent crop after the incorporation of green manures. SOC stock decreased with green manures, even though carbon input with green manures, including B, HV and BHV, was greater than that with C. The mean value of the SOC stock change factor for green manure crops, including B, HV and BHV was 0.627 and was significantly lower than that of the C. However, the net GWP also decreased with the incorporation of green manure crops, and the mean value of the relative net GWP index across B, HV and BHV was 0.853. These conflicting results were caused by different estimation methods between annual SOC change (△SOC) and net GWP. The estimation of SOC stock change using △SOC suggested by the IPCC method may overestimate the contribution of green manure crops to global warming. The net GWP method with comprehensive input and output of carbon in the soil system could provide a better understanding of the carbon balance in soil systems. In the current study, the comparison of △SOC and net GWP was conducted for at one site of upland soil for 5 years. Therefore, further research on estimating the effect of green manure crops on net GWP in various types of soil for longer years should be conducted.

Rationally Designed Li-Ag Alloy with In-Situ-Formed Solid Electrolyte Interphase for All-Solid-State Lithium Batteries.

All-solid-state lithium batteries (ASSLBs) with sulfide-based solid electrolytes have attracted significant attention as promising energy storage devices, owing to their high energy density and enhanced safety. However, the combination of a lithium metal anode and a sulfide solid electrolyte results in performance degradation, owing to lithium dendrite growth and the side reactions of lithium metal with the solid electrolyte. To address these issues, a Ag-based Li alloy with a favorable solid electrolyte interphase (SEI) was prepared using electrodeposition and applied to the ASSLB as an anode. The electrochemically formed SEI layer on the Li-Ag alloy primarily comprised LiF and Li2O with high mechanical strength and Li3N with high ionic conductivity, which suppressed the formation of lithium dendrites and short-circuiting of the cell. The symmetric cell with the Li-Ag alloy achieved a critical current density of 1.6 mA cm-2 and maintained stable cycling for over 2000 h at a current density of 0.6 mA cm-2. Consequently, the all-solid-state lithium cell assembled with the Li-Ag alloy anode with SEI, Li6PS5Cl solid electrolyte, and LiNi0.78Co0.10Mn0.12O2 cathode delivered a high discharge capacity of 185 mAh g-1 and exhibited good cycling performance in terms of cycling stability and rate capability at 25 °C.

Nano-anticoagulant based on carrier-free low molecular weight heparin and octadecylamine with an albumin shuttling effect.

Low-molecular-weight heparin (LMWH), derived from unfractionated heparin (UFH), has enhanced anticoagulant efficacy, long duration of action, and extended half-life. Patients receiving LMWH for preventive therapies would strongly benefit from its long-term effects, however, achieving this is challenging. Here, we design and evaluate a nanoengineered LMWH and octadecylamine conjugate (LMHO) that can act for a long time while maintaining close to 97 ± 3% of LMWH activity via end-specific conjugation of the reducing end of LMWH. LMHO can self-assemble into nanoparticles with an average size of 105 ± 1.7 nm in water without any nanocarrier and can be combined with serum albumin, resulting in a lipid-based albumin shuttling effect. Such molecules can circulate in the bloodstream for 4-5 days. We corroborate the self-assembly capability of LMHO and its interaction with albumin through molecular dynamics (MD) simulations and transmission electron microscopy (TEM) analysis. This innovative approach to carrier-free polysaccharide delivery, enhanced by nanoengineered albumin shuttling, represents a promising platform to address limitations in conventional therapies.