African swine fever, caused by African swine fever virus (ASFV), is a highly contagious and fatal disease that poses a significant threat to the global pig industry. The limited information on ASFV pathogenesis and ASFV-host interactions has recently prompted numerous transcriptomic studies. However, most of these studies have focused on elucidating the transcriptome profiles of ASFV-infected porcine alveolar macrophages in vitro. Here, we analyzed dynamic transcriptional patterns in vivo in nine organ tissues (spleen, submandibular lymph node, mesenteric lymph node, inguinal lymph node, tonsils, lungs, liver, kidneys, and heart) obtained from pigs in the early stages of ASFV infection (1 and 3 d after viremia). We observed rapid spread of ASFV to the spleen after viremia, followed by broad transmission to the liver and lungs and subsequently, the submandibular and inguinal lymph nodes. Profound variations in gene expression patterns were observed across all organs and at all time-points, providing an understanding of the distinct defence strategies employed by each organ against ASFV infection. All ASFV-infected organs exhibited a collaborative response, activating immune-associated genes such as S100A8, thereby triggering a pro-inflammatory cytokine storm and interferon activation. Functional analysis suggested that ASFV exploits the PI3K-Akt signalling pathway to evade the host immune system. Overall, our findings provide leads into the mechanisms underlying pathogenesis and host immune responses in different organs during the early stages of infection, which can guide further explorations, aid the development of efficacious antiviral strategies against ASFV, and identify valuable candidate gene targets for vaccine development.
Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.
Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.
Recent amendments to regulatory frameworks have placed a greater emphasis on the utilization of in vitro testing platforms for preclinical drug evaluations and toxicity assessments. This requires advanced tissue models capable of accurately replicating liver functions for drug efficacy and toxicity predictions. Liver organoids, derived from human cell sources, offer promise as a reliable platform for drug evaluation. However, there is a lack of standardized quality evaluation methods, which hinders their regulatory acceptance. This paper proposes comprehensive quality standards tailored for liver organoids, addressing cell source validation, organoid generation, and functional assessment. These guidelines aim to enhance reproducibility and accuracy in toxicity testing, thereby accelerating the adoption of organoids as a reliable alternative or complementary tool to animal testing in drug development. The quality standards include criteria for size, cellular composition, gene expression, and functional assays, thus ensuring a robust hepatotoxicity testing platform.
BACKGROUND AND PURPOSE: Chitinase-3-like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti-CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. EXPERIMENTAL APPROACH: The effect of CHI3L1 antibody on phthalic anhydride-induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis-related cytokines were determined using an enzyme-linked immunosorbent assay, and RT-qPCR, STAT3 and CXCL8 signalling were measured by western blotting. KEY RESULTS: Anti-CHI3L1 antibody suppressed phthalic anhydride-induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride-induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride-treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis-related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL-4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein-association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL-1ß, IL-4, CXCL8, TSLP, and the expression of CHI3L1 and p-STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p-STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. CONCLUSION AND IMPLICATIONS: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis.
OBJECTIVE: This study aimed to propose treatment protocol and identify patterns of tillaux fractures using three-dimensional (3D) computed tomography (CT) analysis and to describe an effective reduction technique. METHODS: Forty-two juvenile patients with tillaux fractures were evaluated with 3D-CT scan for fracture displacement pattern and received surgical treatment. Tillaux fragment was reduced by pushing the superomedial quadrant part of the fragment slightly downward towards the ankle joint from anterolateral to posteromedial through 5-mm skin incisions with mosquito forceps. A 4.0 cannulated screw was subsequently inserted from the anterolateral to the posteromedial side parallel to the ankle joint. We analysed the distance and direction of fracture displacement with 3D-CT before the surgery. Pre-operative and post-operative plain radiographs were evaluated. RESULTS: Pre-operative 3D-CT analysis revealed a common fracture pattern, varus tilt, and external rotation of fragment. We achieved satisfactory reduction with residual fracture gaps less than 2 mm in 42 cases. Two cases had a 13-mm anterior gap that was reduced by mini-open reduction because of periosteal impingement. No significant clinical complications were found. CONCLUSION: The closed reduction technique developed based on the fracture pattern identified by 3D-CT anatomical analysis is safe and effective in treating tillaux fractures.
BACKGROUND: Acupuncture is known for a harmless treatment when administered by well-trained clinicians. However, multiple case reports of traumatic adverse events (AEs) related to acupuncture treatments continue to be published in literature. In this review, we evaluated the reporting quality and conducted causality assessments of case studies that have reported acupuncture-related traumatic AEs in Korea. METHODS: Eight databases were searched from their inception to January 2024. Only Korean case studies that reported traumatic AEs following acupuncture procedures were included without any language restrictions. Reporting quality was evaluated based on patient characteristics, AEs, and acupuncture practice. Causality was assessed using the modified WHO-UMC causality criteria. RESULTS: Twenty-eight studies were included from a total of 1,154 identified studies. The quality of reporting in the included studies was low overall. While the descriptions of patient characteristics and AEs were relatively well detailed, most information on acupuncture practice was not reported at all. During the causality assessment, only three (10.7%) studies were judged to be "certain". Twelve (42.9%) studies were "unassessable" because they inadequately described the information necessary for decision-making. It was practically difficult to establish the causality between acupuncture and AEs, as well as the appropriateness of acupuncture practice. CONCLUSIONS: Insufficient and inappropriate reporting was observed in most case studies reporting acupuncture-related traumatic AEs in Korea. To overcome these limitations, we have suggested tentative guidelines in the form of a set of items that should be reported by future authors who plan to publish case studies on acupuncture-related traumatic AEs in a clinical setting.
Acupuncture Therapy , Humans , Acupuncture Therapy/adverse effects , Acupuncture Therapy/methods , Databases, Factual , Republic of Korea
BACKGROUND: Although there are several studies in the development of various human cancers, the role of exosomes is poorly understood in the progression of gallbladder cancer. This study aims to characterize the metabolic changes occurring in exosomes obtained from patients with gallbladder cancer compared with those from other gallbladder disease groups. METHODS: Biliary exosomes were isolated from healthy donors (n = 3) and from patients with gallbladder cancer (n = 3), gallbladder polyps (n = 4), or cholecystitis (n = 3) using a validated exosome isolation kit. Afterward, we performed miRNA profiling and untargeted metabolomic analysis of the exosomes. The results were validated by integrating the results of the miRNA and metabolomic analyses. RESULTS: The gallbladder cancer group exhibited a significant reduction in the levels of multiple unsaturated phosphatidylethanolamines and phosphatidylcholines compared to the normal group, which resulted in the loss of exosome membrane integrity. Additionally, the gallbladder cancer group demonstrated significant overexpression of miR-181c and palmitic acid, and decreased levels of conjugated deoxycholic acid, all of which are strongly associated with the activation of the PI3K/AKT pathway. CONCLUSIONS: Our findings demonstrate that the contents of exosomes are disease-specific, particularly in gallbladder cancer, and that altered metabolites convey critical information regarding their phenotype. We believe that our metabolomic and miRNA profiling results may provide important insights into the development of gallbladder cancer.
Exosomes , Gallbladder Neoplasms , MicroRNAs , Humans , Gallbladder Neoplasms/genetics , Phosphatidylinositol 3-Kinases/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Exosomes/metabolism
This study aimed to investigate adsorption effects of electron scavengers (H2O2 and S2O82-) on oxidation performance for mineralization of sulfamethoxazole (SMX) in radiation treatment using catalysts (Al2O3, TiO2). Hydrogen peroxide (H2O2, 1 mM) as an electron scavenger showed weak adsorption onto catalysts (0.012 mmol g-1-Al2O3 and 0.004 mmol g-1-TiO2, respectively), leading to an increase in TOC removal efficiency of SMX within the absorbed dose of 30 kGy by 12.3% with Al2O3 and by 8.0% with TiO2. The weak adsorption of H2O2 onto the catalyst allowed it to act as an electron scavenger, promoting indirect decomposition reactions. However, high adsorption of S2O82- (1 mM) onto Al2O3 (0.266 mmol g-1-Al2O3) showed a decrease in TOC removal efficiency of SMX from 76.2% to 30.2% within the absorbed dose of 30 kGy. The high adsorption of S2O82- onto the catalyst inhibited direct decomposition reaction by reducing adsorption of SMX on catalysts. TOC removal efficiency for Al2O3 without electron scavengers in an acidic condition was higher than that in a neutral or alkaline condition. However, TOC removal efficiency for Al2O3 with S2O82- was higher in a neutral condition than in other pH conditions. This indicates that the pH of a solution plays a critical role in the catalytic oxidation performance by determining surface charges of catalysts and yield of reactive radicals produced from water radiolysis. In the radiocatalytic system, H2O2 enhances the oxidation performance of catalysts (Al2O3 and TiO2) over a wide pH range (3-11). Meanwhile, S2O82- is not suitable with Al2O3 in acidic conditions because of its strong adsorption onto Al2O3 in this study.
Sulfamethoxazole , Water Pollutants, Chemical , Sulfamethoxazole/chemistry , Hydrogen Peroxide/chemistry , Adsorption , Electrons , Water Pollutants, Chemical/analysis , Oxidation-Reduction , Catalysis
In this study, a one-step immunoassay for porcine epidemic diarrhea virus (PEDV) based on Fv-antibodies and switching peptides was developed, and the assay results of PEDV were obtained by just mixing samples without any further reaction or washing steps. The Fv-antibodies with binding affinity to the spike protein of PEDV were screened from the Fv-antibody library using the receptor-binding domain (RBD) of the spike protein as a screening probe. Screened Fv-antibodies with binding affinities to the RBD antigen were expressed, and the binding constants (KD) were calculated to be 83-142 nM. The one-step immunoassay for the detection of PEDV was configured as a displacement immunoassay using a fluorescence-labeled switching peptide. The one-step immunoassay based on switching peptides was performed using PEDV, and the limit of detection (LOD) values for PEDV detection were estimated to be Ct = 39.7-36.4. Compared with the LOD value for a conventional lateral flow immunoassay (Ct = 33.0), the one-step immunoassay showed a remarkably improved LOD for the detection of PEDV. Finally, the interaction between the screened Fv-antibodies and the PEDV RBD was investigated using docking simulations and compared with the amino acid sequences of the receptors on host cells, such as aminopeptidase N (APN) and angiotensin-converting enzyme-2 (ACE-2).
Porcine epidemic diarrhea virus , Animals , Swine , Porcine epidemic diarrhea virus/metabolism , Spike Glycoprotein, Coronavirus , Immunoassay/methods , Peptides , Antibodies, Viral
BACKGROUND: New variants of the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic continue to emerge. However, little is known about the effect of these variants on clinical outcomes. This study evaluated the risk factors for poor pulmonary lung function test (PFT). METHODS: The study retrospectively analyzed 87 patients in a single hospital and followed up by performing PFTs at an outpatient clinic from January 2020 to December 2021. COVID-19 variants were categorized as either a non-delta variant (November 13, 2020-July 6, 2021) or the delta variant (July 7, 2021-January 29, 2022). RESULTS: The median age of the patients was 62 years, and 56 patients (64.4%) were male. Mechanical ventilation (MV) was provided for 52 patients, and 36 (41.4%) had restrictive lung defects. Forced vital capacity (FVC) and diffusion capacity of the lung for carbon monoxide (DLCO ) were lower in patients on MV. Male sex (odds ratio [OR], 0.228) and MV (OR, 4.663) were significant factors for decreased DLCO . The duration of MV was associated with decreased FVC and DLCO . However, the type of variant did not affect the decrease in FVC (P=0.750) and DLCO (P=0.639). CONCLUSIONS: Among critically ill COVID-19 patients, 40% had restrictive patterns with decreased DLCO . The reduction of PFT was associated with MV, type of variants.
Monocarboxylate transporter-1 (MCT-1) inhibitors were screened from the Fv-antibody library, which contained complementary determining region 3 with randomized amino acid sequences (11 residues) through site-directed mutagenesis. Fv-antibodies against MCT-1 were screened from the autodisplayed Fv-antibody library. Two clones were screened, and the binding affinity (KD) against MCT-1 was estimated using flow cytometry. The screened Fv-antibodies were expressed as soluble fusion proteins (Fv-1 and Fv-2) and the KD for MCT-1 was estimated using the SPR biosensor. The inhibitory activity of the expressed Fv-antibodies was observed in HEK293T and Jurkat cell lines by measuring intracellular pH and lactate accumulation. The level of cell viability in HEK293T and Jurkat cell lines was decreased by the inhibitory activity of the expressed Fv-antibodies. The binding properties of the Fv-antibodies to MCT-1 were analyzed using molecular docking simulations. Overall, the results showed that the screened Fv-antibodies against MCT-1 from the Fv-antibody library had high binding affinity and inhibitory activity against MCT-1, which could be used as potential therapeutic drug candidates for the MCT-1 inhibitor.
Antibodies , Carrier Proteins , Humans , Molecular Docking Simulation , HEK293 Cells , Amino Acid Sequence , Gene Library
BACKGROUND: Coronavirus disease 2019 (COVID-19) vaccination is effective in preventing the disease transmission and progression. However, the relatively mild disease course of the omicron variant and the decrease in antibodies over time after vaccination raise questions about the effectiveness of vaccination, especially in young people. We compared the prevalence of pneumonia and chest X-ray severity score according to vaccination status among patients < 50 years old with COVID-19. METHODS: From January 17 to March 17, 2022, 579 patients with COVID-19, who were < 50 years old and had a known vaccination history in our institution, were all included in this study. All patients underwent initial chest radiography, and follow-up chest radiographs were obtained every two days until discharge. Pneumonia was scored from the radiographs using the Brixia scoring system. The scores of the six lung zones were added for a total score ranging from 0 to 18. Patients were divided into four groups according to 10-year age intervals. Differences between groups were analyzed using the χ² or Fisher's exact tests for categorical variables and the Kruskal-Wallis test or analysis of variance for continuous variables. RESULTS: Among patients aged 12-19 years, the prevalence of pneumonia did not differ depending on vaccination status (non-vaccinated vs. vaccinated, 1/47 [2.1%] vs. 1/18 [5.6%]; P = 0.577). Among patients in their 20s, the prevalence of pneumonia was significantly higher among non-vaccinated patients than among vaccinated patients (8/28, 28.6% vs. 7/138, 5.1%, P < 0.001), similar to patients in their 40s (32/52 [61.5%] vs. 18/138 [13.0%]; P < 0.001). The chest X-ray severity score was also significantly higher in non-vaccinated patients than that in vaccinated patients in their 20s to their 40s (P < 0.001), but not among patients aged 12-19 years (P = 0.678). CONCLUSION: In patients aged 20-49 years, vaccinated patients had a significantly lower prevalence of pneumonia and chest X-ray severity score than non-vaccinated patients.
COVID-19 , Humans , Adolescent , Middle Aged , COVID-19/epidemiology , SARS-CoV-2 , Prevalence , Retrospective Studies , Radiography , Vaccination
Objective: In sham acupuncture-controlled acupuncture clinical trials, although sham acupuncture techniques are different from those of verum acupuncture, the same acupuncture points are often used for verum and sham acupuncture, raising the question of whether sham acupuncture is an appropriate placebo. We aimed to examine the effects of sham and verum acupuncture according to the points needled (same or different between verum and sham acupuncture) in knee osteoarthritis. Methods: Ten databases were searched to find randomized controlled clinical trials (RCTs) assessing the effects of verum acupuncture with sham acupuncture or waiting lists on knee osteoarthritis. Sham acupuncture was classified as using the same acupuncture points as those in verum acupuncture (SATV) or using sham points (SATS). A frequentist network meta-analysis (NMA) was conducted, and the certainty of evidence was evaluated. Results: A total of 10 RCTs involving 1628 participants were included. Verum acupuncture was significantly superior to SATS but not different from SATV in terms of pain reduction. Additionally, SATV was significantly superior to the waiting list. For physical function, no difference were found between verum acupuncture, SATV, and SATS. The certainty of evidence was low to moderate. Conclusion: For knee osteoarthritis, the pain reduction effect of acupuncture may differ according to the needling points of sham acupuncture, and the control group should be established according to the specific aim of the study design and treatment mechanism.
This study aims to compare changes of corneal topography (Galilei G4) before and after the instillation of artificial tears in patients with dry eye disease (DED). Corneal topography was performed in patients 1 min before and after artificial tear instillation. Two types of artificial tears were used: 1% polysorbate 80 (PSB) and 0.5% carboxymethylcellulose (CMC). Of 135 patients, PSB and CMC were instilled in 101 and 34 eyes, respectively. The average value of Sim K increased significantly after instillation (44.07 ± 2.26 diopter (D)) compared to before (43.90 ± 2.02 D, p = 0.006) the instillation of artificial tears. Mean Sim K astigmatism was statistically increased after PSB instillation (1.48 ± 2.17 D) compared to before instillation (1.31 ± 2.10 D, p = 0.049). An axis change of astigmatism 10° or more after artificial tear instillation was found in 51.9% of patients, and 30° or more in 20.0% of patients. Increased Sim K value and significant changes in the astigmatic axis in the corneal topography were observed after instillation of artificial tears in DED patients. PSB instillation had a greater effect on corneal keratometry values than CMC instillation.
Serotonin-like mimotopes were screened from the Fv-antibody library to be used as inhibitors against monoamine oxidase A (MAO-A). The Fv-antibody [corresponding to the VH region of immunoglobulin G (IgG)] consists of three complementarity-determining regions and four frame regions. The Fv-antibody library was prepared by site-directed mutagenesis of CDR3, which consists of 11 amino acid residues. Three target clones were screened from the Fv-antibody library, and the binding affinity of the screened clones to the monoclonal anti-serotonin antibody was analyzed using fluorescence-activated cell sorting. The screened Fv-antibodies were expressed as soluble proteins fused with green fluorescence protein. Additionally, the screened CDR3 regions (11 residues) of the selected Fv-antibodies were synthesized as peptides with linking amino acid residues. The binding constants (KD) of the three serotonin-like mimotopes (Fv-antibodies and peptides) were estimated using a surface plasmon resonance biosensor. The inhibitory activity (IC50) of the serotonin-like mimotopes (Fv-antibodies and peptides) was estimated separately for MAO-A and MAO-B enzymes and compared with that of conventional inhibitors. Finally, the screened serotonin-like mimotopes were used to treat a cell line (SH-SY5Y, ATCC code: CRL-2266) expressing serotonin receptors. This was done to confirm the following two aspects: (1) the binding of mimotopes to the serotonin receptors on the cell surface and (2) the inhibitory activity of mimotopes against MAO-A enzymes in the cell lysates.
Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer's disease, and atherosclerosis. Several studies have shown that CHI3L1 can be considered as a marker of disease diagnosis, prognosis, disease activity, and severity. In addition, the proinflammatory action of CHI3L1 may be mediated via responses to various proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1ß, interleukin-6, and interferon-γ. Therefore, CHI3L1 may contribute to a vast array of inflammatory diseases. However, its pathophysiological and pharmacological roles in the development of inflammatory diseases remain unclear. In this article, we review recent findings regarding the roles of CHI3L1 in the development of inflammatory diseases and suggest therapeutic approaches that target CHI3L1.
Chitinases , Neoplasms , Humans , Chitinase-3-Like Protein 1/genetics , Neoplasms/genetics , Neoplasms/metabolism , Inflammation/metabolism , Cytokines
Nucleosomes, the basic structural units of chromatin, hinder recruitment and activity of various DNA repair proteins, necessitating modifications that enhance DNA accessibility. Poly(ADP-ribosyl)ation (PARylation) of proteins near damage sites is an essential initiation step in several DNA-repair pathways; however, its effects on nucleosome structural dynamics and organization are unclear. Using NMR, cryoelectron microscopy (cryo-EM), and biochemical assays, we show that PARylation enhances motions of the histone H3 tail and DNA, leaving the configuration of the core intact while also stimulating nuclease digestion and ligation of nicked nucleosomal DNA by LIG3. PARylation disrupted interactions between nucleosomes, preventing self-association. Addition of LIG3 and XRCC1 to PARylated nucleosomes generated condensates that selectively partition DNA repair-associated proteins in a PAR- and phosphorylation-dependent manner in vitro. Our results establish that PARylation influences nucleosomes across different length scales, extending from the atom-level motions of histone tails to the mesoscale formation of condensates with selective compositions.
Nucleosomes , Poly ADP Ribosylation , Nucleosomes/genetics , Poly ADP Ribosylation/genetics , Poly(ADP-ribose) Polymerases/metabolism , Cryoelectron Microscopy , Biomolecular Condensates , DNA Repair , Histones/genetics , Histones/metabolism , DNA/genetics , DNA/metabolism , DNA Damage , Poly (ADP-Ribose) Polymerase-1/metabolism
PURPOSE: To compare union rate, union time, alignment, and complication rate in ipsilateral tibia plateau and shaft fractures treated via suprapatellar intramedullary nailing with screw fixation and minimally invasive locking plate fixation. MATERIALS AND METHODS: A retrospective study was conducted on 48 patients who underwent minimally invasive plate fixation (n = 35) or suprapatellar intramedullary nailing with screw fixation (n = 13), for the treatment of ipsilateral tibial plateau and shaft fractures with at least 1-year follow-up. Union rate, union time, radiologic alignment, and complication rate such as malalignment, nonunion, and fracture-related infection (FRI) were investigated. RESULTS: Demographic data were not different between the two groups. Coronal plane alignment was 0.17 ± 4.23 in the plate group and -0.48 ± 4.17 in the intramedullary nail group (p = 0.637). Sagittal plane alignment was -0.13 ± 5.20 in the plate group and -1.50 ± 4.01 in the suprapatellar intramedullary nail group (p = 0.313). Coronal and sagittal malalignment recorded equal results: (p > 0.99), FRI (p = 0.602), nonunion and union times recorded (p = 0.656) and (p = 0.683, 0.829), respectively, and showed no significant difference between the two groups. CONCLUSION: Suprapatellar intramedullary nailing with screw fixation had similar surgical outcomes with minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures in terms of union rate, union time, alignment, and complication rate. Thus, frequent use of intramedullary nailing combined with screw fixation is anticipated in patients with ipsilateral tibial plateau and shaft fractures when the soft tissue condition is not desirable. LEVEL OF EVIDENCE: Level III.
Fracture Fixation, Intramedullary , Tibial Fractures , Humans , Tibia , Bone Nails , Retrospective Studies , Tibial Fractures/surgery , Bone Screws , Treatment Outcome
BACKGROUNDS: It is unclear which patients benefit from resection in intermediate-stage-hepatocellular carcinoma (HCC). The authors aimed to identify high-risk patients for early recurrence among patients with resectable intermediate-stage HCC. METHODS: This multicenter retrospective study included patients who underwent resection or trans-arterial chemoembolization (TACE) for intermediate-stage HCC (2008-2019). Multivariable Cox proportional analysis was performed to identify high-risk patients when treated with resection. A prediction score for 2-year recurrence-free survival (RFS) was developed using the training cohort and validated. The 2-year RFS in each risk group was compared with that in TACE group, after propensity score matching (PSM). RESULTS: A total of 1686 patients were included (480 and 1206 patients in the resection and TACE groups). During a median follow-up of 31.4 months, the 2-year RFS was significantly higher in the resection (47.7%) than in the TACE group (19.8%) [adjusted hazard ratio (aHR)=1.471, 95% CI: 1.199-1.803, P <0.001). On multivariate analysis, alpha-fetoprotein ≥5.0 ng/ml (aHR=0.202), ALBI grade ≥2 (aHR=0.709), tumor number ≥3 (aHR=0.404), and maximal tumor size ≥5 cm (aHR=0.323) were significantly associated with the lower risk of 2-year RFS in the resection group. The newly developed Surgery Risk score in BCLC-B (SR-B score) with four significant risk factors showed an area under the curve of 0.801 for the 2-year RFS and was validated. Based on the SR-B score, low-risk patients had a significantly higher 2-year RFS (training: aHR=5.834; validation: aHR=5.675) than high-risk patients (all P <0.001) did. In a PSM cohort, a low-risk resection group had a significantly higher (aHR=3.891); a high-risk resection group had a comparable 2-year RFS to those treated with TACE (aHR=0.816). CONCLUSIONS: Resection may be beneficial for resectable intermediate-stage HCC based on the SR-B score.
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Retrospective Studies , Neoplasm Staging , Prognosis , Hepatectomy , Propensity Score
