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SUMMARYCarbapenem-resistant Acinetobacter baumannii (CRAB) are an increasing infectious threat in hospitals. We investigated the clinical epidemiology of CRAB infections vs. colonization in patients, and examined the mechanisms of resistance associated with elevated minimum inhibitory concentrations (MICs) for carbapenems. From January to June 2009, 75 CRAB strains were collected. CRAB infection was significantly associated with malignancy and a high APACHE II score. The most dominant resistance mechanism was ISAba1 preceding OXA-51, producing strains with overexpression of efflux pump. Strains carrying blaOXA-23-like enzymes had higher carbapenem MICs than those carrying blaOXA-51-like enzymes; however, the presence of multiple mechanisms did not result in increased resistance to carbapenems. There was no difference in the resistance mechanisms in strains from infected and colonized patients. The majority of strains were genetically diverse by DNA macrorestriction although there was evidence of clonal spread of four clusters of strains in patients. [ABSTRACT FROM AUTHOR]

Introduction: Prognosis in patients undergoing resection for lung and gastrointestinal cancers may differ, depending on the microscopic involvement of surgical margins. Linear staplers, widely used for pulmonary or bowel resection, consist of three rows of fasteners on both sides of a resection line. Although multiple rows of fasteners ensure stump and specimen closure, specimen could compromise accurate pathological evaluation of the true surgical margin. We aimed to compare the novel asymmetrical linear stapler (NALS) with the symmetrical linear stapler (SLS) in a porcine model for stump security and accurate pathological evaluation., Materials and Methods: We used the NALS with three and two rows of staples on the stump and specimen sides, respectively. We performed small bowel resection in a porcine model using the NALS and examined hemostasis of resection margin, tightness of stumps under a specific burst pressure, distances between the true resection margin and staple line, and pathology of the resection margin. An SLS was used as the control., Results: No bleeding was observed at the tissue site after initial blotting of the stapler line with either stapler type. The staplers endured a burst pressure of 3.6 kPa for 15 s without leakage. The distance between the cutting edge and staple line for two rows was significantly greater than the distance between the cutting edge and the nearest staple line for three rows., Conclusions: The NALS is safe and may be more accurate than is SLS for the pathological evaluation of true surgical margins., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Cancer-associated fibroblasts (CAFs) play key roles in the tumor microenvironment. IgA contributes to inflammation and dismantling antitumor immunity in the human liver. In this study, we aimed to elucidate the effects of the IgA complex on CAFs in Pil Soo Sung the tumor microenvironment of HCC., Approach and Results: CAF dynamics in HCC tumor microenvironment were analyzed through single-cell RNA sequencing of HCC samples. CAFs isolated from 50 HCC samples were treated with mock or serum-derived IgA dimers in vitro. Progression-free survival of patients with advanced HCC treated with atezolizumab and bevacizumab was significantly longer in those with low serum IgA levels ( p <0.05). Single-cell analysis showed that subcluster proportions in the CAF-fibroblast activation protein-α matrix were significantly increased in patients with high serum IgA levels. Flow cytometry revealed a significant increase in the mean fluorescence intensity of fibroblast activation protein in the CD68 + cells from patients with high serum IgA levels ( p <0.001). We confirmed CD71 (IgA receptor) expression in CAFs, and IgA-treated CAFs exhibited higher programmed death-ligand 1 expression levels than those in mock-treated CAFs ( p <0.05). Coculture with CAFs attenuated the cytotoxic function of activated CD8 + T cells. Interestingly, activated CD8 + T cells cocultured with IgA-treated CAFs exhibited increased programmed death-1 expression levels than those cocultured with mock-treated CAFs ( p <0.05)., Conclusions: Intrahepatic IgA induced polarization of HCC-CAFs into more malignant matrix phenotypes and attenuates cytotoxic T-cell function. Our study highlighted their potential roles in tumor progression and immune suppression., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Study Design: Retrospective study., Objectives: To validate the sagittal age-adjusted score (SAAS) in predicting proximal junctional kyphosis/failure (PJK/F) and good clinical outcomes following adult spinal deformity (ASD) surgery., Summary of Background Data: SAAS is a relatively new assessment system that incorporates age-adjusted sagittal parameters of pelvic incidence (PI) - lumbar lordosis (LL), pelvic tilt (PT), and T1 pelvic angle (TPA) to predict the PJK/F. External validation is required to verify its clinical usefulness., Methods: We included patients with ASD undergoing ≥5-level fusion including the sacrum or pelvis. SAAS was calculated based on the scores of the three components: PI-LL, PT, and TPA. PJK/F rates and clinical outcomes were compared among the correction categories (undercorrection, matched correction, and overcorrection) for the SAAS as well as for each of the three components. PJK/F rates were compared according to the correction groups of the sagittal components and total SAAS using the chi-square test. Receiver operating characteristic (ROC) analysis was performed to evaluate the predictive ability of overcorrection to develop PJK/F for the three sagittal parameters and SAAS. PROMs at final follow-up were compared among correction groups using ANOVA with Bonferroni post-hoc corrections., Results: A total 411 patients were included in the study (mean age: 69.3 y, mean body mass index: 25.9 kg/m2, total levels fused: 7.7 levels, and follow-up duration: 43.3 mo). Postoperative SAAS categories were as follow: undercorrection (13.4%), matched correction (30.2%), and overcorrection (56.4%). The PJK/F rates were significantly higher in the overcorrection group relative to PI-LL component (P=0.001) as well as SAAS (P=0.038) compared to undercorrection or matched correction groups. The clinical outcomes were best in patients who achieved matched correction relative to PI-LL component as well as SAAS compared to the other correction groups. However, the differentiating power of clinical outcomes across the correction categories was greater in the PI-LL component than in the SAAS., Conclusion: This study validated the efficacy of SAAS system to differentiate PJK/F development and good clinical outcomes. However, its differentiating power seems to be largely attributable to the function of the PI-LL component, as the PI-LL correction status better predicted PJK/F risk and clinical outcomes than SAAS., Competing Interests: Conflict of interest disclosure: nothing to disclose, (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background/aim: Macrophages prevail in the microenvironment of several tumors, including non-small-cell lung cancer (NSCLC), where they secrete pro-tumorigenic factors that contribute to cancer progression. This study investigated the role of macrophages on the resistance of epidermal growth factor receptor (EGFR)-mutated NSCLC cells to tyrosine kinase inhibitors (TKIs)., Materials and Methods: EGFR-mutated cell lines PC-9 and HCC827 were cocultured with macrophages and treated with TKIs (erlotinib and gefitinib). The effects of the macrophage-conditioned medium (macrophage CM) on gefitinib resistance and cell migration were also evaluated., Results: Co-culture with macrophages significantly enhanced the resistance to erlotinib and gefitinib in PC-9 and HCC827 cells compared to that in cells cultured independently. Macrophage CM markedly induced gefitinib resistance in PC-9 cells, with maximum resistance observed at 50% CM concentration. This resistance persisted for up to 48 h post-CM removal. Macrophage CM inhibited gefitinib-induced apoptosis, as evidenced by the decreased expression of cleaved caspase-3, PARP, and BIM. Additionally, macrophage CM increased the migration ability of PC-9 cells, as shown by the wound healing and transwell migration assays. Studies have shown that TonEBP is crucial in cancer metastasis and drug resistance; we found that inhibition of TonEBP/NFAT5 expression reduced gefitinib resistance and migration in macrophage CM-induced PC-9 cells, indicating its role as mediator of these effects., Conclusion: Macrophages contribute to TKI resistance and enhance the migration of EGFR-mutated NSCLC cells through mechanisms involving TonEBP/NFAT5. Therefore, targeting TonEBP/NFAT5 represents a potential therapeutic strategy for overcoming macrophage-induced TKI resistance in NSCLC cells., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

While steroid therapy is the preferred treatment for severe alcohol-associated hepatitis, the role of effector regulatory T (eTreg) cells and their association with steroid response and clinical outcomes in these patients remains to be elucidated. We prospectively enrolled 47 consecutive patients with alcohol-associated hepatitis, consisting of severe alcohol-associated hepatitis treated with steroids (n=18; steroid-treated group) and mild alcohol-associated hepatitis (n=29; nontreated group). After isolating peripheral blood mononuclear cells from the patients at enrollment and again 7 days later, the frequency of eTreg cells was examined using flow cytometry. Single-cell RNA sequencing analysis was conducted using paired peripheral blood mononuclear cells. In vitro experiments were also performed to assess phenotype changes and the suppressive function of Treg cells following steroid treatment. The steroid-treated group exhibited significantly higher Model for End-Stage Liver Disease scores than the nontreated group ( p < 0.01). Within the steroid-treated group, the proportion of eTreg cells significantly expanded in the steroid responders (n=13; p = 0.01). Furthermore, a significant positive correlation was observed between the decrease in the Model for End-Stage Liver Disease score and the increase in eTreg cells ( p < 0.05). Single-cell RNA sequencing using paired peripheral blood mononuclear cells (pre-steroid and post-steroid therapy) from a steroid responder revealed gene expression changes in T cells and monocytes, suggesting enhancement of Treg cell function. In vitro results showed an elevation in the proportion of eTreg cells after steroid therapy. In conclusion, our findings suggest that the efficacy of steroid therapy in patients with severe alcohol-associated hepatitis is mediated by an increase in the number of eTreg cells., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Microplastics (MPs) pollution has recently become a major concern for agroecosystems. The interplay between MPs, and heavy metal(loid)s in the soil can intensify the risks to plant growth and human health. The current study investigated the interactive effects of arsenic (As) and biodegradable and petroleum-based conventional MPs on rice growth, As bioavailability, soil bacterial communities, and soil enzyme activities. As-contaminated soil (5 mg kg -1 ) was treated with conventional MPs i.e., polystyrene (PS) and polyethylene (PE) and biodegradable MPs i.e., polylactic acid (PLA) and polybutylene adipate terephthalate (PBAT) at 0.1 % and 1 % rates. In a pot experiment, rice plants were cultivated in soil co-contaminated with As and MPs. PLA-MPs exhibited significant interactions with As, increasing its bioavailability and impairing rice plant growth by enhancing plant oxidative stress. The results illustrated that T2 treatment (PLA-MPs @ 1 % + As 5 mg kg -1 ) significantly decreased the root and shoot lengths, root and shoot dry weights as well as the rates of photosynthesis, transpiration, intercellular CO 2 , and stomatal conductance in rice plants. Biodegradable PLA-MPs @ 1 % resulted in increased uptake of As in rice roots, stems, and leaves by 13.4 %, 38.9 %, and 20.6 %, respectively. In contrast, conventional PE-MPs @ 1 % showed contradictory results with As uptake declined by 2.2 %, 5.1 %, and 9.9 % in rice roots, stem and leaves. Soil enzyme kinetics showed that biodegradable MPs increased the activities of soil catalase, dehydrogenase, and phytase enzymes, whereas both conventional PS and PE-MPs decreased their activities. Moreover, As and PLA-MPs combined stress altered soil bacterial communities by increasing the relative abundance of Protobacteria, Acidobacteria, Chloroflexi, and Firmicutes phyla by 49 %, 29 %, 82 %, and 57 %, respectively. This study provides new insights into MPs-As interactions in soil-plant system and ecological risks associated with their coexistence., Competing Interests: Declaration of competing interest We declare that we do not have any conflicts of financial or non-financial interests, and we have all agreed to submit the article for publication., (Copyright © 2024 Elsevier B.V. All rights reserved.)

HCC (Hepatocellular carcinoma) is the most common malignant tumor; however, the molecular pathogenesis of these tumors is not well understood. Sorafenib, an approved treatment for HCC, inhibits angiogenesis and tumor cell proliferation. However, only ~30% of patients are sensitive to sorafenib and most show disease progression, indicating resistance to sorafenib. The present study used machine learning to investigate several mechanisms related to sorafenib resistance in liver cancer cells. This revealed that unphosphorylated interferon-stimulated genes (U-ISGs) were upregulated in sorafenib-resistant liver cancer cells, and the unphosphorylated ISGF3 (U-ISGF3; unphosphorylated STAT1, unphosphorylated STAT2 and IRF9) complex was increased in sorafenib-resistant liver cancer cells. Further study revealed that the knockdown of the U-ISGF3 complex downregulated U-ISGs. In addition, inhibition of the U-ISGF3 complex downregulated cell viability in sorafenib-resistant liver cancer cells. These results suggest that U-ISGF3 induced sorafenib resistance in liver cancer cells. Also, this mechanism may also be relevant to patients with sorafenib resistance., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Seo et al.)

Background: The internal mammary artery (IMA) is the most commonly used graft in coronary artery bypass grafting (CABG) because of its superior long-term patency rate. However, its small diameter poses challenges in handling, and any vascular damage that may occur during harvesting can significantly affect surgical outcomes. The primary focus during IMA harvesting is to ensure safe and effective hemostasis without direct vascular injury, while ensuring secure and reliable ligation of the vascular branches. Various methods using multiple surgical instruments have been used for this purpose. Unlike traditional instruments, the shear-tip Harmonic scalpel offers more precise vessel branching control, while minimizing damage to surrounding tissues. In this study, we assessed the utility of the shear-tip Harmonic scalpel in patients undergoing minimally invasive coronary artery bypass grafting (MICABG)., Methods: From April 2019 to May 2023, a total of 40 patients underwent MICABG. The IMA was harvested using the shear-tip Harmonic scalpel with a clipless skeletonized technique. In this cohort, 5 patients underwent complete endoscopic harvesting, while 34 patients underwent direct visualization harvesting through minimal thoracotomy. Graft patency was assessed by measuring a Doppler flowmeter in the bypass conduit., Results: Successful graft patency was achieved in all patients. The mean duration of IMA harvesting was 87 min. In total, 38 of the 40 patients underwent MICABG without the need for cardiopulmonary bypass, ensuring a stable procedure. There were no graft-related events or complications observed in any of the patients, and all were discharged without any issues. During a median follow-up period of 15.2 months, only one patient experienced graft occlusion necessitating intervention., Conclusions: The utilization of shear-tip Harmonic scalpel for IMA harvesting in MICABG is feasible and yields stable early results., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1810/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

Background: The etiology and pathology of mucoid degeneration of the anterior cruciate ligament (MD-ACL) remain poorly understood. MD-ACL may be associated with knee osteoarthritis (OA) or a mechanism other than OA. This study evaluated the radiological differences between knees with MD-ACL and those with a normal ACL and compared the clinical and radiological features of knees with MD-ACL according to the knee OA status., Methods: This retrospective study compared the radiological features of the intercondylar notch width index (NWI) and posterior tibial slope (PTS) of 67 MD-ACL patients (MD group) and 67 age-, sex-, and OA grade-matched patients with a normal ACL (control group). During the subgroup analysis, MD-ACL patients were divided into the non-OA subgroup (n = 41) and OA subgroup (n = 26). The pain location and characteristics of the knee, PTS, and NWI were compared between these subgroups., Results: Compared to the control group, the MD group had a lower NWI (0.26 ± 0.03 vs. 0.28 ± 0.01, p < 0.001) and a larger PTS (11.3° ± 3.0° vs. 9.2° ± 2.5°, p < 0.001). During the subgroup analysis, the most common pain locations were the posterior and medial aspects of the knee in the non-OA subgroup (43.9%) and OA subgroup (53.8%), respectively. Pain on terminal flexion was the most common pain characteristic in both subgroups (non-OA subgroup, 73.1%; OA subgroup, 53.8%). The PTS was not different between subgroups (11.7° ± 3.2° in the non-OA subgroup vs. 10.6° ± 2.7° in the OA subgroup; p = 0.159). However, the non-OA subgroup had a lower NWI than the OA subgroup (0.25 ± 0.03 vs. 0.28 ± 0.02, p = 0.001)., Conclusions: Patients with MD-ACL had a lower NWI and a larger PTS than patients with a normal ACL. Furthermore, the clinical and radiological features of MD-ACL differed according to the knee OA status. A narrow intercondylar notch may be more closely associated with the development of MD-ACL without OA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Background: Perfusion index (PI) has been used as a surrogate marker of sympathetic blockade. This study evaluated changes in PI of bilateral upper extremity after thoracic paravertebral block (PVB) and intertransverse process block (ITPB)., Methods: This pilot study included three groups of patients undergoing elective unilateral pulmonary resection under general anesthesia with PVB (n=11) or ITPB (n=10), or urologic procedures with general anesthesia (control group, n=10). Blockades were performed using 10 mL aliquots of 0.5% ropivacaine administered at T3-4, T5-6, and T7-8 intercostal levels immediately after general anesthesia induction. The PI value of the operating side (PI-O) was divided by the contralateral side (PI-CL), and the relative change to baseline was assessed (relative PI-O/PI-CL), with a 50% increase considered meaningful., Results: In all cases within the PVB and ITPB groups, a significant increase in PI was observed following the blockades. The median (1Q, 3Q) intraoperative relative PI-O/PI-CL values were 0.9 (0.8, 1.4), 2.1 (1.4, 2.5), and 1.4 (0.9, 1.9) in the control, PVB, and ITPB groups (P=0.01), respectively. Pairwise comparison revealed a significant difference only between the control and PVB groups (adjusted P=0.01). While the relative PI-O/PI-CL value in the control group generally remained close to 1, occasional fluctuations exceeding 1.5 were noted., Conclusions: PVB induced a noticeable unilateral increase in upper extremity PI, whereas ITPB tended to result in an inconsistent and lesser degree of increase. Monitoring PI values can serve as an indicator of upper extremity sympathetic blockade, but consideration of potential confounders impacting these observations during surgery is essential. Further research is needed to validate these findings., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-69/coif). The authors have no conflicts of interest to declare., (2024 Journal of Thoracic Disease. All rights reserved.)

The environmental impact of biodegradable polylactic acid microplastics (PLA-MPs) has become a global concern, with documented effects on soil health, nutrient cycling, water retention, and crop growth. This study aimed to assess the repercussions of varying concentrations of PLA-MPs on rice, encompassing aspects such as growth, physiology, and biochemistry. Additionally, the investigation delved into the influence of PLA-MPs on soil bacterial composition and soil enzyme activities. The results illustrated that the highest levels of PLA-MPs (2.5%) impaired the photosynthesis activity of rice plants and hampered plant growth. Plants exposed to the highest concentration of PLA-MPs (2.5%) displayed a significant reduction of 51.3% and 47.7% in their root and shoot dry weights, as well as a reduction of 53% and 49% in chlorophyll a and b contents, respectively. The activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), and ascorbate peroxidase (APX) in rice leaves increased by 3.1, 2.8, 3.5, and 5.2 folds, respectively, with the highest level of PLA-MPs (2.5%). Soil enzyme activities, such as CAT, urease, and dehydrogenase (DHA) increased by 19.2%, 10.4%, and 22.5%, respectively, in response to the highest level of PLA-MPs (2.5%) application. In addition, PLA-MPs (2.5%) resulted in a remarkable increase in the relative abundance of soil Proteobacteria, Nitrospirae, and Firmicutes by 60%, 31%, and 98.2%, respectively. These findings highlight the potential adverse effects of PLA-MPs on crops and soils. This study provides valuable insights into soil-rice interactions, environmental risks, and biodegradable plastic regulation, underscoring the need for further research., Competing Interests: Declaration of competing interest We declare that we do not have any conflicts of financial or non-financial interests, and we have all agreed to submit the article for publication., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Although guidelines and protocols are available for central venous access, existing methods lack specificity and sensitivity, especially when placing peripherally inserted central catheters (PICCs). We evaluated the feasibility of catheter detection in the right atrial cavity using transthoracic echocardiography (TTE) during PICC placement., Methods: This single-center, retrospective study included consecutive patients who underwent PICC placement between January 2022 and March 2023. TTE was performed to detect the arrival of the catheter in the right atrial cavity. Catheter misplacement was defined as an aberrant catheter position on chest x-ray (CXR). The primary endpoint was predicting catheter misplacement based on catheter detection in the right atrial cavity. The secondary endpoint was optimizing catheter placement and examining catheter-associated complications., Results: Of the 110 patients identified, 10 were excluded because of poor echogenicity and vein access failure. The remaining 100 patients underwent PICC placement with TTE. The catheter was visualized in the right atrial cavity in 90 patients. CXR exams revealed catheter misplacement in seven cases. Eight patients with catheter misplacement underwent the same procedure in the other arm. In two patients, PICC placement failed due to anatomical reasons. Catheter misplacement was detected using TTE with sensitivity, specificity, positive predictive value, and negative predictive value of 97% confidence interval (CI; 91.31%-99.36%), 90% CI (55.50%-99.75%), 99%, and 75%, respectively., Conclusions: TTE is a reliable tool for detecting catheter misplacement and optimizing catheter tip positioning during PICC placement.

Background: Sepsis is an important cause of acute kidney injury in intensive care unit patients, accounting for 15% to 20% of renal replacement therapy prescriptions. The neutrophil-lymphocyte ratio (NLR), a marker of systemic inflammation and immune response, was previously associated with the mortality rate in multiple conditions. Herein, we aimed to examine how the NLR relates to the mortality rate in septic acute kidney injury patients requiring continuous renal replacement therapy (CRRT)., Methods: The NLRs of 6 and 18 were used for dividing NLRs into three groups and, thus, were set higher than those in previous studies accounting for steroid use in sepsis. Cox proportional hazard models were used to calculate hazard ratios of mortality outcomes before and after matching their propensity scores., Results: A total of 798 septic acute kidney injury patients requiring CRRT were classified into three NLR groups (low, <6 [n = 277]; medium, ≥6 and <18 [n = 115], and high, ≥18 [n = 406], respectively). The in-hospital mortality rates per group were 83.4%, 74.8%, and 70.4%, respectively (p < 0.001). Per the univariable Cox survival analysis after propensity score matching, a high NLR was related to approximately 24% reduced mortality. The survival benefit of the high NLR group compared with the other two groups remained consistent across all subgroups, showing any p for interactions of >0.05., Conclusion: A high NLR is associated with better clinical outcomes, such as low mortality, in septic acute kidney injury patients undergoing CRRT.

Background: Macrophages promote angiogenesis, metastasis, and drug resistance in several cancers. Similarly, TonEBP/NFAT5 induces metastasis in renal carcinoma and colon cancer cells. However, the role of this transcription factor and that of macrophages in lung cancer cells remains unclear. Therefore, this study investigated the effects of macrophages and TonEBP/NFAT5 expression on cisplatin resistance and migration in A549 lung adenocarcinoma cells., Results: A549 cells were cultured alone or indirectly co-cultured with THP-1-derived macrophages using a transwell culture chamber. Cisplatin-induced cell death was markedly decreased and migration increased in co-cultured A549 cells. Macrophage-conditioned media (CM) showed a similar effect on drug resistance and migration. Cisplatin-induced apoptosis, DNA fragmentation, and cleaved apoptotic proteins PARP and caspase-3 were markedly reduced in macrophage CM-induced A549 cells. Here, ERK, p38, JNK, and NF-κB activities were increased by macrophage CM. Furthermore, the proteins involved in cisplatin resistance and cancer cell migration were identified using specific inhibitors of each protein. ERK and NF-κB inhibition considerably reduced cisplatin resistance. The increase in macrophage CM-induced migration was partially reduced by treatment with ERK, JNK, and NF-κB inhibitors. TonEBP/NFAT5 expression was increased by macrophages, resulting in increased cisplatin resistance, cell migration, and invasion. Moreover, RNAi-mediated knockdown of TonEBP/NFAT5 reduced cisplatin resistance, migration, and invasion in macrophage CM-induced A549 cells., Conclusions: These findings demonstrate that paracrine factors secreted from macrophages can change A549 cells, resulting in the induction of drug resistance against cisplatin and migration. In addition, the TonEBP/NFAT5 ratio, increased by macrophages, is an important regulator of the malignant transformation of cells., (© 2024. The Author(s).)

Background: Adjusting the direction of the anterolateral ligament (ALL) femoral tunnel is suggested to avoid tunnel convergence during anterior cruciate ligament (ACL) reconstruction. Yet, there has been no in vivo clinical study reporting the effect of changing the direction of the ALL tunnel on the incidence of convergence with the ACL tunnel., Purpose: To report the incidence of convergence between the ACL femoral tunnel and a distally and anteriorly directed ALL femoral tunnel and to determine a safe distal angle and anterior angle., Study Design: Cross-sectional study; Level of evidence, 3., Methods: A total of 227 patients undergoing concomitant ALL and anatomic single-bundle ACL reconstruction between January 2020 and December 2022 were retrospectively reviewed. The tunnel convergence rate, angular orientation of the tunnels, and distance between tunnels were obtained using postoperative computed tomography. The patients were grouped based on the direction of the ALL tunnel (transverse vs distal anterior) and the presence of tunnel convergence (convergence vs no convergence)., Results: The overall tunnel convergence rate was 53.3% (121/227 patients). Tunnel convergence was observed less frequently in the distal anterior group (33.7%) than in the transverse group (65.2%) ( P < .001). The no convergence group showed an ALL tunnel oriented more distally (20.2°± 11.1°) and anteriorly (19.5°± 10.2°) compared with the convergence group (8.7°± 6.5° and 6.9°± 5.3°, respectively) ( P = .005 and P = .008, respectively). There were no cases of tunnel convergence for ALL tunnels >24.3° distally and >25.5° anteriorly. There was no difference in the angle of the ACL femoral tunnel between all groups., Conclusion: A distally and anteriorly directed ALL femoral tunnel reduced the incidence of convergence with the ACL femoral tunnel. A distal angle >24.3° and an anterior angle >25.5° of an ALL tunnel are suggested to safely avoid convergence with the ACL tunnel., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This work was supported by grants from the Korea Medical Device Development Fund (funded by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety) (project No. 1415181807, RS-2021-KD000001, and RS-2020-KD000297). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.

Purpose: Residual anterior knee pain is one of the most common problems after total knee arthroplasty (TKA). However, the contributing factors affecting postoperative anterior knee pain (AKP) remain poorly understood. This study aimed to evaluate the effect of preoperative patellar bone marrow lesions (BMLs) and patellar cartilage defects on postoperative AKP after patellar non-resurfacing TKA., Methods: This retrospective study included 336 patients who underwent unilateral TKA without patella resurfacing. All patients underwent preoperative magnetic resonance imaging (MRI) to assess the presence of BMLs and the degree of cartilage defects in the patella. Patients were categorized into four groups according to the presence of BMLs (with or without BMLs) and the degree of cartilage defects (with or without full thickness cartilage defects). The Kujala Anterior Knee Pain Scale (AKPS) and the Hospital for Special Surgery Knee Rating Scale (HSS) scores at 2 years after TKA were compared among the groups., Results: Preoperative BMLs in the patella were found in 132 (39.3%) of 336 cases. Among the four groups, the group with both BMLs and full-thickness cartilage defects demonstrated significantly lower AKPS compared to the other groups at 2 years after TKA (p < 0.01), but no significant difference was shown in the HSS scores, between these groups. There were no significant differences in either AKPS or HSS scores among the other three patient groups., Conclusions: The presence of preoperative BMLs with full-thickness cartilage defects in the patella was associated with worse postoperative AKP after TKA without patella resurfacing. Patella resurfacing should be considered in this patient group to minimize the risk of developing residual AKP after TKA., Level of Evidence: III., (© 2023. The Author(s) under exclusive licence to European Society of Sports Traumatology, Knee Surgery, Arthroscopy (ESSKA).)

Background and Objectives : Intravenous (IV) non-opioid analgesics (NOAs) have been extensively investigated as a multimodal analgesic strategy for the management of acute pain after hip surgery. This pair-wise meta-analysis examined IV NOA effects following hip surgery. Materials and Methods : A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies investigating the effect of IV NOA for postoperative pain management following hip surgery up to 7 June 2023. We compared in-admission opioid use, postoperative VAS (visual analogue scale) score, hospital stay duration, and opioid-related adverse events between IV NOA and control groups. Results : Seven studies were included with a total of 953 patients who underwent hip surgery. Of these, 478 underwent IV NOA treatment, and 475 did not. The IV NOA groups had lower opioid use within 24-h following hip surgery (SMD, -0.48; 95% CI, -0.66 to -0.30; p < 0.01), lower VAS score (SMD, -0.47; 95% CI, -0.79 to -0.16; p < 0.01), shorter hospital stay (SMD, -0.28; 95% CI, -0.44 to -0.12; p < 0.01), and lower incidence of nausea and vomiting (OR, 0.32; 95% CI, 0.15 to 0.67; p < 0.01) compared with the control groups. Conclusions: This meta-analysis demonstrated that IV NOA administration following hip surgery may have more favorable postoperative outcomes than those in control groups.

Soil erosion has become a worldwide problem that threatens the environment and the future of economic and social development. The purpose of this study is to investigate the contribution of steep slopes and gullies to erosion in high precipitation tropical areas of the Ethiopian highlands. A trapezoidal weir was installed at the head and tail of the gully to monitor the discharge and sediment concentration from 2017 to 2020. Sediment yield and runoff are heavily influenced by the amount and timing of precipitation. The coefficients of variation for total sediment loads ranged from 65.1 to 96.1% at the head and 17.1-78.1% at the tail; the lowest coefficients were found in 2018 and the highest in 2020. Furthermore, 85% of the sediment at the tail comes from the gully, according to the four-year sediment budget. Further, a hysteretic analysis of suspended sediment concentration and runoff revealed that hilly sediment sources are limited (clockwise), then sediment can be transported through the gully via bank failures (counterclockwise). Study findings contributed to a classification of runoff patterns and an investigation of suspended sediment dynamics. In the gully tail, sediment yield was higher than in the head, suggesting gully sediment contributed more to sediment yield than large upland catchments. As a result of the study, we have been able to develop practical recommendations for managing gully erosion in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Soils pollution with heavy metals (HMs) is a serious concern due to their toxic effects on crop yield, crop quality, soil environment, and human health. In the current study, four stabilizers of calcium carbonate (CC), dolomite (DL), zeolite (ZL), and steel slag (SS) were applied to cadmium (Cd) and lead (Pb)-contaminated soils as in-situ chemical remediation techniques along with in-situ physical remediation techniques i.e. soil covering (SC) and soil dilution (SD) under real field conditions. For three years, Chinese cabbage (Brassica rapa L.) was grown on the amended fields to examine how the amendments impacted Cd and Pb uptake in plants. The stabilization efficiency of SS, CC, and SC were 75.7 %, 66.0 %, and 71.1 %, respectively, for Cd, and 55.6 %, 55.6 %, and 70.0 %, respectively, for Pb. Results indicated that stabilizer soil amendments significantly decreased the exchangeable (F1) and carbonates bound (F2) fractions of both Cd and Pb. For instance, F1 fraction of Cd decreased from 10.2 (control) to 1.8-2.9 % (with stabilizers). The stabilizers increased Chinese cabbage dry weight by 11.4-22.5 % and decreased Cd and Pb uptake by 67.4 % and 24 %, respectively. The results demonstrated that in-situ chemical remediation technique showed promising results and maintained its efficiency for more than 130 weeks. Current study indicated that chemical remediation of Cd and Pb contaminated soil is more effective and last longer than physical remediation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary., Methods: We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration., Results: Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin . Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance., Conclusions: Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1110/coif). XL is from GZ Runsheng CytoMed Technology Co. Ltd. The other authors have no conflicts of interest to declare., (2023 Journal of Thoracic Disease. All rights reserved.)

Study Objective: The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection., Design: Single-center, double-blinded, randomized, non-inferiority trial., Setting: Operating room and intensive care unit or ward in a tertiary hospital., Patients: Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection., Interventions: Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4-5 and T6-7 intercostal levels immediately after the induction of general anesthesia., Measurements: The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery., Main Results: Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was -5.27 (95% confidence interval [CI], -15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups., Conclusions: The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure., Competing Interests: Declaration of competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Objectives : The anterior-based muscle-sparing (ABMS) approach, which utilizes the interval between the tensor fasciae latae posteriorly, offers several advantages, such as the reduced risk of nerve injury and the freedom to choose various implants. Herein, we aimed to compare the outcome of ABMS to the direct anterior (DA) approach using pairwise meta-analysis techniques. Materials and Methods : A systematic search of the MEDLINE (PUBMED), Embase, and Cochrane Library databases was performed for studies published up to 7 June 2023, which compared the ABMS approach with the DA approach for hip arthroplasty. We compared (1) perioperative outcomes (operation time, visual analog scale (VAS) score, total opioid consumption, length of hospital stay (LOS), and the number of patients discharged to their homes); (2) postoperative complications (neuropraxia/nerve injury, dislocation, surgical site infection, intraoperative fracture, and reoperation rate); and (3) implant position (cup inclination, cup anteversion, and stem alignment). Results : Ten studies were eligible for meta-analysis, including 1737 patients who underwent hip arthroplasty with the ABMS approach and 1979 with the DA approach. The pooled analysis showed no differences in all outcome variables, including perioperative outcomes, postoperative complications, and the implant position between the two surgical approaches. Conclusions: In current meta-analysis, the ABMS approach demonstrated comparable results to the conventional DA approach in terms of both clinical and radiologic outcomes as well as postoperative complications. Furthermore, the ABMS approach has the advantage of a broader indication and fewer limitations in terms of the surgical position compared to the DA approach. Therefore, the ABMS approach can be even more beneficial as an option within MSA, surpassing the utility of the DA approach.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer ( n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% ( n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

Background and Objectives: Total knee arthroplasty (TKA) involves blood loss, increasing the risk of postoperative anemia and delayed functional recovery. Intravenous (IV) iron supplementation limits postoperative anemia; however, the effectiveness of IV iron, administered one day before TKA, on postoperative anemia and functional recovery has scarcely been studied. Materials and Methods: We conducted a retrospective cohort study with propensity score matching using two consecutive groups of patients who underwent TKA using tranexamic acid: the iron group received 500 mg ferric derisomaltose intravenously one day before surgery (n = 46); the non-iron group did not (n = 46). Hemoglobin (Hb) level was determined at postoperative days (PODs) 2, 4, 6, 14, and 30. Ferritin, transferrin saturation (TSAT), and functional iron deficiency anemia (IDA) rate were measured at PODs 2, 4, 6, and 14. Length of hospital stay and transfusion rate were also evaluated. Results: The iron group had higher Hb levels at PODs 6, 14, and 30 and higher ferritin and TSAT at PODs 2, 4, 6, and 14. The functional IDA rate was significantly higher in the non-iron group at PODs 2, 4, 6, and 14. Length of hospital stay was significantly shorter in the iron group; however, the rate of transfusion did not differ between the two groups. Conclusions: IV iron administered one day before TKA was associated with postoperative anemia recovery and length of hospital stay; however, it did not lower the postoperative transfusion rate.

Background: Despite efforts to treat critically ill patients who require continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI), their mortality risk remains high. This condition may be attributable to complications of CRRT, such as arrhythmias. Here, we addressed the occurrence of ventricular tachycardia (VT) during CRRT and its relationship with patient outcomes., Methods: This study retrospectively enrolled 2,397 patients who started CRRT due to AKI from 2010 to 2020 at Seoul National University Hospital in Korea. The occurrence of VT was evaluated from the initiation of CRRT until weaning from CRRT. The odds ratios (ORs) of mortality outcomes were measured using logistic regression models after adjustment for multiple variables., Results: VT occurred in 150 patients (6.3%) after starting CRRT. Among them, 95 cases were defined as sustained VT (i.e., lasting ≥30 seconds), and the other 55 cases were defined as non-sustained VT (i.e., lasting &lt;30 seconds). The occurrence of sustained VT was associated with a higher mortality rate than a nonoccurrence (OR, 2.04 and 95% confidence interval [CI], 1.23-3.39 for the 30- day mortality; OR, 4.06 and 95% CI, 2.04-8.08 for the 90-day mortality). The mortality risk did not differ between patients with non-sustained VT and nonoccurrence. A history of myocardial infarction, vasopressor use, and certain trends of blood laboratory findings (such as acidosis and hyperkalemia) were associated with the subsequent risk of sustained VT., Conclusion: Sustained VT occurrence after starting CRRT is associated with increased patient mortality. The monitoring of electrolytes and acid-base status during CRRT is essential because of its relationship with the risk of VT.

Objective: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure., Methods: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set., Results: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022)., Conclusions: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters., Key Points: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement., (© 2022. The Author(s), under exclusive licence to European Society of Radiology.)

Background: We invest computed tomography (CT) image differences between non-invasive adenocarcinomas (NIAs) and invasive adenocarcinomas (IAs) presenting as pure ground glass nodules (GGNs)., Methods: From 2013 to 2019, 48 pure GGNs were surgically resected in 45 patients. Of these, 40 were pathologically diagnosed as non-small cell lung cancers (NSCLCs). We assessed them using the Synapse Vincent (Fujifilm Co., Ltd., Tokyo, Japan) three-dimensional (3D) analysis system; we drew histograms of the CT densities. We calculated the maximum, minimum, means, and standard deviations of the densities. The proportions of GGNs of high CT density were compared between the two groups. The diagnostic performance was investigated via receiver operating curve (ROC) analysis., Results: Of the 40 pure GGNs, 20 were NIAs (4 adenocarcinomas in situ and 16 minimally IAs) and 20 IAs. Significant correlations were evident between histological invasiveness and the maximum and mean CT densities and the standard deviation. Neither the nodule volume nor the minimum CT density significantly predicted invasiveness. A CT volume density proportion >-300 Hounsfield units optimally predicted the invasiveness of pure GGNs; the cutoff was 5.41% with a sensitivity of 85% and a specificity of 95%., Conclusions: CT density reflected the invasiveness of pure GGNs. A CT volume proportion density >-300 Hounsfield units may significantly predict histological invasiveness., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-2327/coif). The authors have no conflicts of interests to declare., (2023 Translational Cancer Research. All rights reserved.)

Background: Robot-assisted total knee arthroplasty (r-TKA) can reportedly achieve more accurate implant positioning than conventional total knee arthroplasty (c-TKA), although its learning curve is controversial. Moreover, few studies have investigated r-TKA in Asians, who have different anatomical characteristics. This study aimed to determine the learning curve for r-TKA and compare implant positions between r-TKA and c-TKA according to the learning curve in Asian patients., Methods: This prospective study included 50 consecutive c-TKAs (group C), followed by 50 consecutive r-TKAs conducted using the MAKO robotic system (Stryker, USA). Cumulative summation analyses were performed to assess the learning curve for operative time in r-TKA. Accordingly, the r-TKA cases were divided into the initial (group I) and proficiency cases (group P). The femoral and tibial component positions in the coronal, sagittal, and axial planes and lower limb alignment were compared among the three groups., Results: r-TKA was associated with a learning curve for operative time in 18 cases. The operative time was significantly shorter in groups C and P than that in group I, with no significant difference between groups C and P. Groups I and P demonstrated fewer outliers with respect to lower limb alignment, femoral component coronal position, axial position, and tibial component sagittal position than those in group C, with no significant difference between groups I and P., Conclusion: The operative time did not differ significantly between r-TKA and c-TKA after the learning curve. Surgeons could expect more accurate and reproducible lower limb alignment and implant positioning with r-TKA in Asian patients, irrespective of the learning curve., (© 2023. The Author(s).)

Background: Idiosyncratic drug-induced liver injury (DILI) is caused by the interplay among drugs, their metabolites, and the host immune response. The characterization of infiltrated immune cells in the liver may improve the understanding of the pathogenesis of idiosyncratic DILI. This study investigated the phenotypes and clinical implications of liver-infiltrating immune cells in idiosyncratic DILI., Methods: From January 2017 to June 2021, 53 patients with idiosyncratic DILI who underwent liver biopsy were prospectively enrolled in this study. Immunohistochemical staining and flow cytometry analyses were performed on the biopsy specimens. Serum levels of CXC chemokine ligand 10 (CXCL10) and soluble CD163 were measured. A multivariate cox proportional hazards model was used to evaluate predictors of DILI resolution within 30 days., Results: The numbers of intrahepatic T cells and mononuclear phagocytes were positively correlated with serum levels of total bilirubin, alanine aminotransferase (ALT), and the model of end-stage liver disease score. The frequency of activated CD8+ T cells among liver-infiltrating CD8+ T cells in DILI livers was higher than that in healthy livers. Notably, the percentages of activated intrahepatic CD8+ T cells and mononuclear phagocytes in DILI livers showed a positive correlation with ALT. Additionally, serum CXCL10 level was positively correlated with intrahepatic T cell infiltration and ALT, and soluble CD163 level was positively correlated with intrahepatic mononuclear phagocyte infiltration and ALT. Thirty-six patients (70.6%) were treated with steroids. In multivariate analysis, total bilirubin and steroid use independently influenced DILI resolution within 30 days., Conclusions: Activated CD8+ T cells and mononuclear phagocyte are associated with liver injury caused by drugs. Therefore, we suggest that steroids are a potential treatment option for idiosyncratic DILI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yang, Han, Lee, Lee, Cho, Rho, Kang, Jang, Jung, Choi, Sung and Bae.)

Background: Several studies suggest improved outcomes for patients with kidney disease who consult a nephrologist. However, it remains undetermined whether a consultation with a nephrologist is related to a survival benefit after starting continuous renal replacement therapy (CRRT) due to acute kidney injury (AKI)., Methods: Data from 2,397 patients who started CRRT due to severe AKI at Seoul National University Hospital, Korea between 2010 and 2020 were retrospectively collected. The patients were divided into two groups according to whether they underwent a nephrology consultation regarding the initiation and maintenance of CRRT. The Cox proportional hazards model was used to calculate the hazard ratio (HR) of mortality during admission to the intensive care unit after adjusting for multiple variables., Results: A total of 2,153 patients (89.8%) were referred to nephrologists when starting CRRT. The patients who underwent a nephrology consultation had a lower mortality rate than those who did not have a consultation (HR = 0.47 [0.40-0.56]; P < 0.001). Subsequently, patients who had nephrology consultations were divided into two groups (i.e., early and late) according to the timing of the consultation. Both patients with early and late consultation had lower mortality rates than patients without consultations, with HRs of 0.45 (0.37-0.54) and 0.51 (0.42-0.61), respectively., Conclusions: Consultation with a nephrologist may contribute to a survival benefit after starting CRRT for AKI., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Cataracts and major depressive disorder (MDD) both have high prevalence, representing for major health burdens globally. In this study, we examined the risk of MDD due to cataracts. Data from the 2016 to 2018 Korea National Health and Nutrition Examination Survey (KNHANES) were used, including 4122 participants. Logistic regression analysis was performed to evaluate the odds ratio for MDD in association with cataracts. Controlled variables were age, gender, smoking, dyslipidemia and mobility. Subgroup analysis was performed with stratification by gender. The results reveal that cataracts are significantly correlated with MDD. Elderly people with cataracts were found to be more likely to develop MDD compared to those without cataracts (adjusted odds ratio: 1.654; 95% CI = 1.197-2.286). In subgroup analysis, men (adjusted odds ratio: 2.631; 95% CI = 1.247-5.551) were found to be more likely to develop MDD than women (adjusted odds ratio: 1.510; 95% CI = 1.061-2.150). Cataracts may be a risk factor for MDD in the elderly, especially among the male population.

Background: Hyperlactatemia occurs frequently in critically ill patients, and this pathologic condition leads to worse outcomes in several disease subsets. Herein, we addressed whether hyperlactatemia is associated with the risk of mortality in patients undergoing continuous renal replacement therapy (CRRT) due to acute kidney injury., Methods: A total of 1,661 patients who underwent CRRT for severe acute kidney injury were retrospectively reviewed between 2010 and 2020. The patients were categorized according to their serum lactate levels, such as high (≥ 7.6 mmol/l), moderate (2.1-7.5 mmol/l) and low (≤ 2 mmol/l), at the time of CRRT initiation. The hazard ratios (HRs) for the risk of in-hospital mortality were calculated with adjustment of multiple variables. The increase in the area under the receiver operating characteristic curve (AUROC) for the mortality risk was evaluated after adding serum lactate levels to the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation (APACHE) II score-based models., Results: A total of 802 (48.3%) and 542 (32.6%) patients had moderate and high lactate levels, respectively. The moderate and high lactate groups had a higher risk of mortality than the low lactate group, with HRs of 1.64 (1.22-2.20) and 4.18 (2.99-5.85), respectively. The lactate-enhanced models had higher AUROCs than the models without lactates (0.764 vs. 0.702 for SOFA score; 0.737 vs. 0.678 for APACHE II score)., Conclusions: Hyperlactatemia is associated with mortality outcomes in patients undergoing CRRT for acute kidney injury. Serum lactate levels may need to be monitored in this patient subset., (© 2023. The Author(s).)

Background: Acidosis frequently occurs in severe acute kidney injury (AKI), and continuous renal replacement therapy (CRRT) can control this pathologic condition. Nevertheless, acidosis may be aggravated; thus, monitoring is essential after starting CRRT. Herein, we addressed the longitudinal trajectory of acidosis on CRRT and its relationship with worse outcomes., Methods: The latent growth mixture model was applied to classify the trajectories of pH during the first 24 hours and those of C-reactive protein (CRP) after 24 hours on CRRT due to AKI (n = 1815). Cox proportional hazard models were used to calculate hazard ratios of all-cause mortality after adjusting multiple variables or matching their propensity scores., Results: The patients could be classified into 5 clusters, including the normally maintained groups (1st cluster, pH = 7.4; and 2nd cluster, pH = 7.3), recovering group (3rd cluster with pH values from 7.2 to 7.3), aggravating group (4th cluster with pH values from 7.3 to 7.2), and ill-being group (5th cluster, pH < 7.2). The pH clusters had different trends of C-reactive protein (CRP) after 24 hours; the 1st and 2nd pH clusters had lower levels, but the 3rd to 5th pH clusters had an increasing trend of CRP. The 1st pH cluster had the best survival rates, and the 3rd to 5th pH clusters had the worst survival rates. This survival difference was significant despite adjusting for other variables or matching propensity scores., Conclusions: Initial trajectories of acidosis determine subsequent worse outcomes, such as mortality and inflammation, in patients undergoing CRRT due to AKI., (© 2022. The Author(s).)

Background and Purpose: Although the prevalence of nonalcoholic steatohepatitis (NASH) is rapidly increasing, effective therapy is lacking. Tenofovir alafenamide (TAF) is a widely used antiviral drug for hepatitis B. In this study, we investigated the potential pharmacological effects of TAF on NASH., Experimental Approach: Two different NASH mouse models were established: 1) by subcutaneous injection of streptozotocin (0.2 mg) and feeding the mice a high-fat, high-cholesterol (HFHC) diet, and 2) feeding the mice a choline-deficient, L-amino acid-defined, high-fat (CDAHF) diet., Key Results: Serum alanine aminotransferase and triglyceride levels in TAF-treated NASH mice were significantly lower than those in the mock-treated ones. The livers from the TAF-treated NASH mice showed attenuated mononuclear phagocyte (MP) infiltration compared to those from the mock-treated ones. TAF-treated NASH mice exhibited decreased liver infiltration of activated MPs (IAIE + /PD-L1 + /MerTK + ). In ex vivo experiments using sorted human CD14 + monocytes treated with lipopolysaccharide (LPS) and/or TAF, we confirmed the decreased level of phosphorylated AKT in TAF-treated LPS-stimulated monocytes compared to that in the mock-treated ones. Mouse liver immunoblotting showed that phosphorylation levels of AKT were significantly lower in the TAF-treated NASH group than in the mock-treated group., Conclusion and Implications: TAF exerts anti-inflammatory effects in NASH livers by attenuating AKT phosphorylation in intrahepatic activated MPs. Therefore, TAF may serve as a new therapeutic option for NASH., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sung, Lee, Roh, Kang, Ahn and Yoon.)

In patients with chronic kidney disease (CKD), coronavirus disease 2019 (COVID-19) has a higher mortality rate than the general population; therefore, prevention is vital. To prevent COVID-19 infection, it is important to study individuals' risk aversion behavior. The objective of this study was to understand how the behavioral characteristics of physical distancing, hygiene practice, and exercise changed in patients with CKD during the COVID-19 pandemic and to identify the characteristics of patients who showed weakened or strengthened behavioral changes. We analyzed data from the Study on Kidney Disease and Environmental Chemicals (Clinical Trial No. NCT04679168), that examined a prospective cohort of patients with CKD. This cohort included patients with CKD who visited the participating hospitals for the first time between June and October 2020 and the second time between October 2020 and January 2021. Data on demographics, socio-economic details, and behavioral characteristics were collected through a questionnaire survey. Using a multivariable logistic regression model, we identified whether COVID-19 infection risk perception and previous strong behavioral changes affected behavioral changes during the first and second visits. A total of 277 patients (33.2% females) were included in the analysis. Nine out of 12 behaviors were reinforced at the first visit, and five out of nine reinforced behaviors were weakened at the second visit. A high-risk perception of COVID-19 infection was not associated with the tendency of overall behavioral reinforcement or maintaining behaviors in an enhanced state at the second visit. Strong behavioral changes at the patients' first visit to the hospital were associated with a tendency to strengthen or maintain reinforced behaviors at the second visit (adjusted odds ratio 1.99, 95% confidence interval 1.19-3.34; P = 0.009). Even if the initial COVID-19 risk perception is high, behavioral changes worsen over time. Individuals who showed more active behavioral changes at the beginning of the COVID-19 pandemic tended to maintain reinforced behavior over time. Continuous education and monitoring are needed to maintain changed behaviors, especially in patients with a high initial COVID-19 risk perception., (© 2022. The Author(s).)

Grazing is a major cause of soil erosion and land degradation across many parts of Ethiopia. This study examined the effects of exclosure on subsurface water levels, soil erosion, and the relationship between daily rainfall and subsurface water levels. Piezometers were used to measure subsurface water levels in the exclosure area during 2017-2020. We found that sediment yield, runoff, and the volume of subsurface water vary greatly depending on the exclosure and temporal practices used. Exclosure of grazing land was the most effective sustainable land management practice in reducing runoff and sediment yield. In 2019 and 2020, the subsurface water level continued to rise at piezometers with exclosure, which shows that exclosure contributed to the subsurface water level rising. In addition, piezometers in grazing land and the exclosure indicate that runoff trapped by acacia decurrens trees can contribute to significant differences in subsurface water levels. Higher runoff coefficients were observed in 2017 and 2018 than in 2019 and 2020, indicating that the exclosure greatly affects runoff; therefore, its implementation is vital to reduce runoff and enhance water conservation. Sediment yields measured for 2017, 2018, 2019, and 2020 were 140.45, 133.15, 101.03, and 74.39 g L -1 day -1 , respectively. In 2017 and 2018, sediment yield increased, while in 2019 and 2020 sediment yield decreased because of an exclosure around the gully's cross-section and communal grazing. This study shows that erosion is reduced by exclosure, possibly due to the restoration of protective vegetation cover. This study revealed that a minimum of human and livestock intervention during the study period considerably increased groundwater levels and decreased soil erosion. Generally, the results of this study indicated that exclosure has a considerable impact on runoff and sediment. Therefore, exclosure implementation is vital to reduce runoff and sediment and enhance water conservation, thus supporting the development of effective communal grazing land management measures on the study sites and other similar environmental settings., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

The soil physical properties are deteriorating due to changing rainfall patterns and intensities, as well as climate change-induced temperature fluctuations. Pot experiments were carried out to examine the impacts of synthesized soil amendments on soil water retention and plant growth. Soil amendments (biochar, polyacrylamide (PAM), and moringa) were used at different rates (0 (control), 2.1, 4.2, and 8.3 g kg -1 ) to improve the physical properties of the soil. As a result of soil amendment application, it was found that the mean weight diameter of soil aggregate increased by 188% during the 8.3 g kg -1 treatment, forming stable soil particles. Soil water retention improved by up to 128.9% during the 8.3 g kg -1 treatment, and it was analyzed that it was due to the high surface area of biochar, porosity, and high molecular weight of PAM. Pellet treatment increased all plant growth parameters (height, stem diameter, leaf number, and fresh and dry weight) for both beans and maize. The dry weight of beans (C 3 plant) and maize (C 4 plant) increased by 92.9 and 146.4%, respectively in an 8.3 g kg -1 pot. The soil physical condition was stabilized by the high carbon content of biochar and the improvement of soil coagulation between PAM and moringa. This had a positive effect on the C 4 plant. The findings of this study indicate that if the soil amendments are properly mixed and applied based, they will improve soil stability and plant productivity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Predicting the risk of death in patients admitted to the critical care unit facilitates appropriate management. In particular, among patients who are critically ill, patients with continuous RRT (CRRT) have high mortality, and predicting the mortality risk of these patients is difficult. The purpose of this study was to develop models for predicting the mortality risk of patients on CRRT and to validate the models externally., Methods: A total of 699 adult patients with CRRT who participated in the VolumE maNagement Under body composition monitoring in critically ill patientS on CRRT (VENUS) trial and 1515 adult patients with CRRT in Seoul National University Hospital were selected as the development and validation cohorts, respectively. Using 11 predictor variables selected by the Cox proportional hazards model and clinical importance, equations predicting mortality within 7, 14, and 28 days were developed with development cohort data., Results: The equation using 11 variables had area under the time-dependent receiver operating characteristic curve (AUROC) values of 0.75, 0.74, and 0.73 for predicting 7-, 14-, and 28-day mortality, respectively. All equations had significantly higher AUROCs than the Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation II (APACHE II) scores. The 11-variable equation was superior to the SOFA and APACHE II scores in the integrated discrimination index and net reclassification improvement analyses., Conclusions: The newly developed equations for predicting CRRT patient mortality showed superior performance to the previous scoring systems, and they can help physicians manage patients., Competing Interests: C. Lim reports having an advisory or leadership role as the President Elect, Korean Society of Nephrology. J. Lee reports having an advisory or leadership role with the Kidney Research and Clinical Practice. N. Tangri reports having consultancy agreements with Marizyme, Mesentech Inc., PulseData Inc., Renibus, and Tricida Inc.; reports having an ownership interest in Clinpredict, Klinrisk, Marizyme, Mesentech Inc., PulseData Inc., Quanta, Renibus, and Tricida Inc.; reports receiving research funding from AstraZeneca, Bayer, BI-Lilly, Janssen, Otsuka, and Tricida Inc; reports receiving honoraria from AstraZeneca, Bayer, BI-Lilly, Janssen, Otsuka Pharmaceuticals, and Pfizer; reports patents or royalties with Klinrisk and Marizyme; reports having an advisory or leadership role with Clinpredict, Klinrisk, and Tricida Inc.; reports having other interests or relationships with the National Kidney Foundation; and reports being the founder of Clinpredict and Klinrisk. S. Kim reports having consultancy agreements with Exosome Plus; reports having an advisory or leadership role with the Korean Society of Nephrology, Editorial Board and the Korean Society of Hypertension, Editorial Board; and reports having other interests or relationships with the Korean Society of Nephrology. Y.S. Kim reports having an advisory or leadership role as President, Seoul National University Hospital. All remaining authors have nothing to disclose., (Copyright © 2022 by the American Society of Nephrology.)

Cancer immunotherapy has emerged as one of the most powerful anticancer therapies. However, the details on the interaction between tumors and the immune system are complicated and still poorly understood. Optical fluorescence imaging is a technique that allows for the visualization of fluorescence-labeled immune cells and monitoring of the immune response during immunotherapy. To this end, near-infrared (NIR) light has been adapted for optical fluorescence imaging because it is relatively safe and simple without hazardous ionizing radiation and has relatively deeper tissue penetration into living organisms than visible fluorescence light. In this review, we discuss state-of-the-art NIR optical imaging techniques in cancer immunotherapy to observe the dynamics, efficacy, and responses of the immune components in living organisms. The use of bioimaging labeling techniques will give us an understanding of how the immune system is primed and ultimately developed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Vastus medialis function has been implicated in the development and progression of knee osteoarthritis; however, studies evaluating the influence of its preoperative volume and quality on functional outcomes following total knee arthroplasty (TKA) remain scarce. This study aimed to determine the association between vastus medialis volume, quality, and clinical outcomes after TKA., Methods: Among the patients who underwent unilateral TKA, 92 who had undergone magnetic resonance imaging (MRI) before TKA were included. Preoperative vastus medialis volume and quality were assessed using the cross-sectional area (CSA) and fat infiltration ratio on MRI. Clinical outcomes were evaluated using the Knee Society knee score (KSKS) and Knee Society function score (KSFS) at baseline and 1 year after surgery. The relationships between preoperative CSA, fatty infiltration ratio, and clinical outcomes were analyzed using univariate and multivariate linear regression., Results: Only the fatty infiltration ratio was significantly associated with postoperative KSFS in the univariate linear regression analysis. In the multivariate linear regression analysis, age and fatty infiltration ratio were significantly associated with postoperative KSFS., Conclusions: Increased vastus medialis fat infiltration is associated with worse functional outcomes after TKA. Preserving vastus medialis quality could improve functional outcomes, and surgeons should encourage patients to perform quadriceps strengthening exercises before surgery.

Background: An investigation into the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted., Methods: In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the estimated glomerular filtration rate (eGFR) with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer and driving) were investigated in 329 758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567 460). The findings were replicated with the 321 024 UK White British Biobank participants in the allele-score-based one-sample MR., Results: A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR., Conclusion: Physical activity and television watching causally affect kidney function in the general population., (© The Author(s) 2021. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Further investigation is needed to determine the causal effects of serum bilirubin on the risk of chronic kidney disease (CKD)., Methods: This study is a Mendelian randomization (MR) analysis. Among the well-known single-nucleotide polymorphisms (SNPs) related to serum bilirubin levels, rs4149056 in the SLCO1B1 gene was selected as the genetic instrument for single-variant MR analysis, as it was found to be less related to possible confounders than other SNPs. The association between genetic predisposition for bilirubin levels and estimated glomerular filtration rate (eGFR) or CKD was assessed in 337 129 individuals of white British ancestry from the UK Biobank cohort. Two-sample MR based on summary-level data was also performed. SNPs related to total or direct bilirubin levels were collected from a previous genome-wide association study and confounder-associated SNPs were discarded. The independent CKDGen meta-analysis data for CKD were employed as the outcome summary statistics., Results: The alleles of rs4149056 associated with higher bilirubin levels were associated with better kidney function in the UK Biobank data. In the summary-level MR, both of the genetically predicted total bilirubin {per 5 µmol/L increase; odds ratio [OR] 0.931 [95% confidence interval (CI) 0.871-0.995]} and direct bilirubin [per 1 µmol/L increase; OR 0.910 (95% CI 0.834-0.993)] levels were significantly associated with a lower risk of CKD, supported by the causal estimates from various MR sensitivity analyses., Conclusion: Genetic predisposition for higher serum bilirubin levels is associated with better kidney function. This result suggests that higher serum bilirubin levels may have causal protective effects against kidney function impairment., (© The Author(s) 2022. Published by Oxford University Press on behalf of the ERA.)

The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near-infrared (NIR) fluorescence-guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast-enhancing agents display low on-target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter-mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post-injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non-targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection., (© 2022 Wiley-VCH GmbH.)