Closed reduction and internal fixation for tillaux fractures, based on pre-operative three-dimensional computed tomography.

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.

Metabolomics and miRNA profiling reveals feature of gallbladder cancer-derived biliary extracellular vesicles.

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.

A one-step immunoassay based on switching peptides for diagnosis of porcine epidemic diarrhea virus (PEDV) using screened Fv-antibodies.

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).

Adsorption effects of electron scavengers and inorganic ions on catalysts for catalytic oxidation of sulfamethoxazole in radiation treatment.

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.

Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer.

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.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Suprapatellar intramedullary nail combined with screw fixation has comparable surgical outcomes to minimally invasive locking plate fixation in ipsilateral tibial plateau and shaft fractures.

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.

Identification of patients with favorable prognosis after resection in intermediate-stage-hepatocellular carcinoma.

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.

Different Outcomes According to Needling Point Location Used in Sham Acupuncture for Cancer-Related Pain: A Systematic Review and Network Meta-Analysis.

Numerous acupuncture studies have been conducted on cancer-related pain; however, its efficacy compared to sham acupuncture remains controversial. We confirmed whether the outcome of acupuncture differs according to the needling points of sham acupuncture for cancer-related pain. We searched 10 databases on 23 May 2023 to screen acupuncture trials using sham acupuncture or waiting list as controls for cancer-related pain. Sham acupuncture was classified into two types, depending on whether the needling was applied at the same locations as verum acupuncture (SATV) or not (SATS). A network meta-analysis (NMA) was performed on the basis of a frequentist approach to assess pain severity. Eight studies (n = 574 participants) were included in the review, seven of which (n = 527 participants) were included in the NMA. The pain severity was not significantly different between SATV and verum acupuncture, but verum acupuncture significantly improved pain severity compared to SATS. The risk of bias affecting the comparisons between the verum and sham acupuncture was generally low. Previous acupuncture trials for cancer-related pain showed differing outcomes of sham and verum acupuncture, depending on the needling points of sham acupuncture. The application of SATV cannot be considered a true placebo, which leads to an underestimation of the efficacy of verum acupuncture.

Outcomes of the electromagnetic navigation bronchoscopy using forceps for lung lesion suspected malignancy: A retrospective study.

Many studies have reported electromagnetic navigation bronchoscopy (ENB) diagnostic yields and the importance of size and computed tomography (CT) bronchus sign. This study aimed to determine the diagnostic yield of ENB alone, using forceps biopsy and cytology. We analyzed the factors associated with yield and complications according to gross specimen size. This retrospective study included patients who underwent ENB using forceps for suspected lung lesions on CT between January 2020 and December 2022 in South Korea. Factors related to the ENB diagnostic yield and complications were evaluated, and the impacts of gross specimen size and cytology were analyzed. A total of 276 patients were analyzed. The final diagnostic yield was 75.5% after excluding indeterminate cases. Sensitivity and specificity were 74.2% and 100%, respectively. Pneumothorax developed in 1.4% (4/276) of cases, with no grade 3 or higher bleeding. Univariable analysis showed that the number of biopsies and the size of the gross specimen were related to the diagnosis. Multivariable analyses showed that a larger lesion size on CT was a significant factor for diagnosis. The gross size of the specimens was not significantly associated with epinephrine use. ENB had acceptable diagnostic yield and safety for diagnosing lung lesions with suspected malignancy. Obtaining more tissue through biopsy may not increase bleeding or pneumothorax complications. Identifying patients with lesion characteristics, including CT bronchus sign, would help increase ENB diagnostic yield.

Isolated torsion of fallopian tube with associated torsed paratubal cystadenofibroma: A case report.

Cystadenofibromas (CAF) and adenofibromas (AF) are rare benign gynecologic neoplasms of epithelial origin. They can be composed predominantly of solid fibrous tissue, adenofibromas, or contain cystic components, as seen in cystadenofibromas; which can be further classified by their epithelial cell type (serous, mucinous, etc.). They most commonly arise from the ovary; however, CAF/AF associated with the fallopian tube have also been reported. CAF/AF is typically asymptomatic and found incidentally. Like other adnexal and ovarian masses, patients are at increased risk of ovarian/adnexal torsion, with increasing risk with lesion size. Herein, we present the case of a patient with isolated torsion of a fallopian tube with associated torsed paratubal serous cystadenofibroma. To our knowledge, this is the first reported case of isolated torsion of a fallopian tube with associated para-tubal cystadenofibroma.

Rotational stability can be enhanced in revision anterior cruciate ligament reconstruction using the over-the-top augmentation technique compared to single bundle technique.

PURPOSE: Revision anterior cruciate ligament (ACL) reconstruction is technically challenging due to mispositioned tunnels, bone loss, and tunnel enlargement, which may compromise graft fixation and result in failure. To obtain firm graft fixation and strength in one stage, we utilized an over-the-top augmentation technique using an Achilles tendon allograft in revision ACL reconstruction (OA-ACLR). This study compared OA-ACLR with single-bundle ACL reconstruction (SB-ACLR). We hypothesized that OA-ACLR would enhance the postoperative knee joint rotational stability. METHODS: We retrospectively analyzed 47 patients who underwent revisional OA-ACLR and 48 who underwent primary SB-ACLR with minimum follow-up of 6 months. Knee instability was evaluated with the anterior drawer, Lachman, and pivot shift tests preoperatively and at the final follow-up. Side-to-side differences were compared with the non-affected side at the final follow-up. Function was evaluated using the IKDC subjective and Lysholm knee scores preoperatively and at the final follow-up. RESULTS: The groups did not differ in terms of sex, age, BMI, and etiology. There were no significant differences in concomitant surgical procedures, such as meniscectomy and meniscus repair, between the two groups (p = 0.335, > 0.99). Both groups significantly improved in the anterior drawer, Lachman, pivot shift tests, and IKDC and Lysholm knee scores after surgery (all p < 0.001). The OA-ACLR group showed significantly higher rotational stability in the pivot shift test than the SB-ACLR group (p = 0.017). The postoperative side-to-side difference, the IKDC and Lysholm scores showed no significant differences between the groups (p = 0.34, 0.301, 0.438). CONCLUSIONS: OA-ACLR showed enhanced rotational stability with pivot shift test compared to SB-ACLR. It may be considered a useful alternative for revision ACL reconstruction.

Needling Point Location Used in Sham Acupuncture for Chronic Nonspecific Low Back Pain: A Systematic Review and Network Meta-Analysis.

Importance: When sham acupuncture is set as a control in evaluating acupuncture, the sham needling technique is usually different from acupuncture. However, the sham procedure is conducted either at the same points that are used for the acupuncture group or at nonindicated points. Objective: To assess whether the outcome of sham acupuncture varies according to the needling points in sham-controlled trials of acupuncture for chronic nonspecific low back pain (CLBP) as an example. Data sources: Searches of MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and the Allied and Complementary Medicine Database were conducted on February 12, 2023. Study selection: Randomized clinical trials (RCTs) assessing the outcomes of acupuncture in sham acupuncture-controlled or waiting list-controlled trials on CLBP were included. Data extraction and synthesis: Two researchers independently extracted data on study characteristics and outcomes and assessed quality. Sham acupuncture was classified according to whether it was conducted at the same acupuncture points used in the acupuncture group, referred to as sham acupuncture therapy (verum) (SATV) or at different points, referred to as sham acupuncture therapy (sham) (SATS). Clinical similarity, transitivity, and consistency tests were conducted, followed by a random-effects frequentist network meta-analysis (NMA). Main outcomes and measures: The primary outcome was pain, and the secondary outcome was back-specific function. The first assessment after the end of treatment was chosen for analysis. Effect sizes are reported as standardized mean differences (SMD) with 95% CIs. The risk of bias was assessed using the Cochrane risk of bias tool, and the certainty of evidence for findings was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. Results: Ten RCTs involving 4379 participants were included. In comparison with SATS, acupuncture was significantly associated with improvements in both pain (SMD, -0.33; 95% CI, -0.52 to -0.15) and function outcomes (SMD, -0.13; 95% CI, -0.25 to -0.02); however, there were no differences between acupuncture and SATV. In comparison with SATS, SATV was significantly associated with better pain (SMD, -0.45; 95% CI, -0.88 to -0.03) and function outcomes (SMD, -0.30; 95% CI, -0.56 to -0.05). The risk of bias that could affect the interpretation of the results was usually low, and the certainty of evidence was moderate to low. Conclusions and relevance: In this NMA, sham acupuncture needling at the same points as those in acupuncture was not a true placebo control for assessing the efficacy of acupuncture for CLBP and might underestimate the outcome of acupuncture in clinical settings.

Feasibility of Raman spectroscopic identification of gall bladder cancer using extracellular vesicles extracted from bile.

Extracellular vesicles (EVs), which are heterogeneous membrane-based vesicles with bilayer cell membrane structures, could be versatile biomarkers for the identification of diverse diseases including cancers. With this potential, this study has attempted the Raman spectroscopic identification of gall bladder (GB) cancer by directly measuring the EV solution extracted from human bile without further sample drying. For this purpose, bile samples were obtained from four normal individuals and 21 GB polyp, eight hepatocellular carcinoma (HCC), and five GB cancer patients, and EVs were extracted from each of the bile samples. The Raman peak shapes of the EVs extracted from the GB cancer samples, especially the relative intensities of peaks in the 1560-1340 cm-1 range, were dissimilar to those of the samples from the normal, GB polyp, and HCC groups. The intensity ratios of peaks at 1537 and 1453 cm-1 and at 1395 and 1359 cm-1 of the GB cancer samples were lower and higher, respectively, than those of the samples of the remaining three groups. The differences of peak intensity ratios were statistically significant based on the Mann-Whitney U test. DNA/RNA bases, amino acids, and bile salts contributed to the spectra of EVs, and their relative abundances seemed to vary according to the occurrence of GB cancer. The varied metabolite compositions and/or structures of EVs were successfully demonstrated by the dissimilar peak intensity ratios in the Raman spectra, thereby enabling the discrimination of GB cancer.

Comparison of suprapatellar intramedullary nailing versus minimal invasive locked plating for proximal tibia fractures.

PURPOSE: To compare the radiological alignment, union time, union rate, and complication rate between suprapatellar intramedullary nails and minimally invasive locking plate fixation in the treatment of proximal tibial fractures. MATERIALS AND METHODS: We retrospectively analyzed 103 patients who underwent plate fixation (n = 50) or suprapatellar intramedullary nailing (n = 53) for proximal tibial fractures involving the meta-diaphyseal junction between November 2015 and October 2020 at our institution. The union rate, union time, radiologic alignments, and complications, such as malalignment, nonunion, and deep infection, were investigated. RESULTS: The demographic data did not differ between the plate and suprapatellar intramedullary nail groups. The alignment of the coronal plane was 0.24 ± 3.19 in the plate group and - 0.49 ± 2.22 in the intramedullary nail group (p = 0.196). Sagittal plane alignment was - 0.29 ± 4.97 in the plate group and 0.24 ± 4.12 in the intramedullary nail group (p = 0.571), and coronal malalignment (p = 0.196), sagittal malalignment (p = 0.57), deep infection (p = 0.264), nonunion (p = 0.695), union time (p = 0.329), and final union rate (p = 0.699) were not significantly different between groups. CONCLUSION: Compared with the minimally invasive locking compression plate group, the suprapatellar intramedullary nail group yielded comparable results in terms of radiological alignment and complications. Considering that proximal tibial fractures are associated with high-energy trauma and severe soft tissue damage, we believe that a suprapatellar intramedullary nail may be a good alternative. LEVEL OF EVIDENCE: Level III.

Immunoaffinity biosensors for the detection of SARS-CoV-1 using screened Fv-antibodies from an autodisplayed Fv-antibody library.

The detection of severe acute respiratory syndrome coronavirus (SARS-CoV-1) was demonstrated using screened Fv-antibodies for SPR biosensor and impedance spectrometry. The Fv-antibody library was first prepared on the outer membrane of E. coli using autodisplay technology and the Fv-variants (clones) with a specific affinity toward the SARS-CoV-1 spike protein (SP) were screened using magnetic beads immobilized with the SP. Upon screening the Fv-antibody library, two target Fv-variants (clones) with a specific binding affinity toward the SARS-CoV-1 SP were determined and the Fv-antibodies on two clones were named "Anti-SP1" (with CDR3 amino acid sequence: 1GRTTG5NDRPD11Y) and "Anti-SP2" (with CDR3 amino acid sequence: 1CLRQA5GTADD11V). The binding affinities of the two screened Fv-variants (clones) were analyzed using flow cytometry and the binding constants (KD) were estimated to be 80.5 ± 3.6 nM for Anti-SP1 and 45.6 ± 8.9 nM for Anti-SP2 (n = 3). In addition, the Fv-antibody including three CDR regions (CDR1, CDR2, and CDR3) and frame regions (FRs) between the CDR regions was expressed as a fusion protein (Mw. 40.6 kDa) with a green fluorescent protein (GFP) and the KD values of the expressed Fv-antibodies toward the SP estimated to be 15.3 ± 1.5 nM for Anti-SP1 (n = 3) and 16.3 ± 1.7 nM for Anti-SP2 (n = 3). Finally, the expressed Fv-antibodies screened against SARS-CoV-1 SP (Anti-SP1 and Anti-SP2) were applied for the detection of SARS-CoV-1. Consequently, the detection of SARS-CoV-1 was demonstrated to be feasible using the SPR biosensor and impedance spectrometry utilizing the immobilized Fv-antibodies against the SARS-CoV-1 SP.

Optimum selection criteria for secondary cytoreductive surgery in patients with recurrent epithelial ovarian cancer: A multicenter study from the Gynecologic Oncology Research Investigators coLLaborAtion group (GORILLA-3001).

BACKGROUND: To identify those most likely to benefit from secondary cytoreductive surgery (SCS), we evaluated the survival outcomes and factors predictive of prognosis in patients with recurrent ovarian cancer. METHODS: We retrospectively reviewed the medical records of patients with recurrent ovarian cancer treated at five high-volume Korean hospitals between 2010 and 2021. Recurrence characteristics, treatment methods, and potential predictors of survival were compared between the chemotherapy and surgery groups. RESULTS: Among all 670 patients, 88.1% had initial stage III/IV disease, and 215 (32.1%) underwent SCS. Among patients who underwent SCS, only those who achieved complete resection exhibited improved survival. Even in patients with residual disease < 1 cm after SCS, we observed no significant survival benefit (p = 0.942). In the multivariate Cox analysis, residual disease at primary surgery, progression-free interval, recurrence sites (≤3 regions or limited carcinomatosis), ascites, and SCS were significant predictors of survival. Meanwhile, the only factor predictive of complete resection after SCS was recurrence sites (p < 0.001). CONCLUSIONS: The benefits of SCS appear to be exclusive to cases of complete resection. We propose limited regional platinum-sensitive recurrence (≤3 regions or limited carcinomatosis) without ascites as the optimum selection criteria for SCS.

Correlation of monocyte counts with clinical outcomes in idiopathic nonspecific interstitial pneumonia.

Higher blood monocyte counts are related to worse survival in idiopathic pulmonary fibrosis. However, studies evaluating the association between blood monocyte counts and clinical outcomes of idiopathic nonspecific interstitial pneumonia (iNSIP) are lacking. We evaluated the impact of monocyte counts on iNSIP prognosis. iNSIP patients (n = 126; median age, 60 years; female, n = 64 [50.8%]) diagnosed by surgical lung biopsy were enrolled and categorized into low (monocyte < 600/µL) and high (monocyte ≥ 600/µL) monocyte groups. The median follow-up duration was 53.0 months. After adjusting for age, sex, and smoking history, the annual decline in forced vital capacity (FVC) showed differences between the monocyte groups (Pinteraction = 0.006) (low vs. high; - 28.49 mL/year vs. - 65.76 mL/year). The high-monocyte group showed a worse survival rate (P = 0.01) compared to low monocyte group. The 5-year survival rates were 83% and 72% in the low- and high-monocyte groups, respectively. In the Cox-proportional hazard analysis, older age, male sex, low baseline FVC, and diffusing capacity of the lung for carbon monoxide were independent risk factors for mortality. However, monocyte count (Hazard ratio 1.61, P = 0.126) was not an independent prognostic factor. Although high monocyte count might be associated with faster lung function decline, it could not independently predict survival in iNSIP.

TGF-ß2 antisense oligonucleotide enhances T-cell mediated anti-tumor activities by IL-2 via attenuation of fibrotic reaction in a humanized mouse model of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, with high mortality and recurrence rate. In this study, we generated a human immune system mouse model by transplanting human peripheral blood mononuclear cells into NSG-B2m mice followed by xenografting AsPC-1 cells, after which we assessed the role of transforming growth factor-ß2 (TGF-ß2) in T-cell-mediated anti-tumor immunity. We observed that inhibiting the TGF-ß2 production by TGF-ß2 antisense oligonucleotide (TASO) combined with IL-2 delays pancreatic cancer growth. Co-treatment of TASO and IL-2 had little effect on the SMAD-dependent pathway, but significantly inhibited the Akt phosphorylation and sequentially activated GSK-3ß. Activation of GSK-3ß by TASO subsequently suppressed ß-catenin and α-SMA expression and resulted in attenuated fibrotic reactions, facilitating the infiltration of CD8 + cytotoxic T lymphocytes (CTLs) into the tumor. TGF-ß2 inhibition suppressed the Foxp3 + regulatory T-cells in peripheral blood and tumors, thereby enhancing the tumoricidal effects of CTLs associated with increased granzyme B and cleaved caspase-3. Moreover, changes in the T-cell composition in peripheral blood and at the tumor site by TASO and IL-2 induced the increase of pro-inflammatory cytokines such as IFN-γ and TNF-α and the decrease of anti-inflammatory cytokines such as TGF-ßs. These results indicate that the TGF-ß2 inhibition by TASO combined with IL-2 enhances the T-cell mediated anti-tumor immunity against SMAD4-mutated PDAC by modulating the tumor-associated fibrosis, suggesting that TASO in combination with IL-2 may be a promising immunotherapeutic intervention for PDAC.

Exposure assessment for pesticide residues in agricultural products consumed in the Republic of Korea during 2016-2020.

Pesticide residues in food comprise compounds such as insecticides, fungicides, herbicides, miticides, and plant activators. The insecticides diazinon (O, O-diethyl O-2-isopropyl-6-methylpyrimidin-4-yl phosphorothioate) and malathion (O, O-dimethyl dithiophosphate of diethyl-mercaptosuccinate) are classified as probably carcinogenic (Group 2A) and the fungicides chlorothalonil (2,4,5,6-tetrachloro-1,3-benzenedicarbonitrile) and hexachlorobenzene (pentachlophenyl chloride) as possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer under the World Health Organization. In this study, gas chromatographic and gas chromatography-tandem mass spectrometric analyses were used to determine the concentrations of pesticide residues in agricultural products and assess the effects of chronic human exposure to pesticide residues through the consumption of agricultural products during 2018-2020. Food consumption data were obtained from the Korea National Health and Nutrition Examination Survey of 2016-2018. The chronic exposures determined using mean consumption data for the whole population and mean concentrations of the pesticide residues were 5.15E-11 to 2.08E-05 [lower bound (LB)] and 2.41E-07 to 4.69E-05 mg/kg bw/day [upper bound (UB)], corresponding to 0.00012-2.16% of the hazard index (HA). Exposures to pesticide residues, calculated using the 95th percentile of the consumption data, were 0-8.76E-05 (LB) and 9.26E-07 to 1.56E-04 mg/kg bw/day (UB), corresponding to 0.00045-9.41% of the HA. Based on the result of current exposure assessment, it could be considered that the pesticide residues in agricultural products are properly controlled by the regulatory authorities.