Intentionally self-injured patients have lower mortality when treated at trauma centers versus non-trauma centers in South Korea.

Objective: This study investigated the characteristics and survival rates of patients with intentional severe trauma (self-harm or suicide) who were transported to either a regional trauma center (TC) or a non-TC facility. Methods: This retrospective, national, population-based, observational, case-control study included patients who sustained intentional severe trauma and had an abnormal Revised Trauma Score at the injury site between January 2018 and December 2019. The data were a community-based severe trauma survey based on data collected from severe injury and multiple casualty patients transported by 119 emergency medical services (EMS), distributed by the Korea Disease Control and Prevention Agency. The treatment hospitals were divided into two types, TC and non-TCs, and several variables, including in-hospital mortality, were compared. Propensity score matching (PSM) was used to mitigate the influence of confounding variables on the survival outcomes. Results: Among the 3864 patients, 872 and 2992 visited TC and non-TC facilities, respectively. The injury severity did not differ significantly between patients treated at TCs and non-TCs (TC, 9; non-TC, 9; p=0.104). However, compared with those treated at non-TCs, patients treated at TCs had a higher rate of surgery or transcatheter arterial embolization (14.2% vs 38.4%; p<0.001) and a higher admission rate to the emergency department (34.4% vs 60.6%; p<0.001). After PSM, 872 patients from both groups were analyzed. Patients treated at TCs exhibited a higher overall survival rate than those treated at non-TCs (76.1% vs 66.9%; p<0.001), and multiple variable logistic regression analysis demonstrated that the causes of injury and transport to the TC were significantly associated. Conclusion: Using Korean EMS data, the results of this study revealed that initial transport to TCs was associated with reduced mortality rates. However, considering the limitations of using data from only 2 years and the retrospective design, further research is warranted. Study type: Retrospective national, population-based observational case-control study. Level of evidence: Level III.

Antiangiogenic Therapeutic mRNA Delivery Using Lung-Selective Polymeric Nanomedicine for Lung Cancer Treatment.

Therapeutic antibodies that block vascular endothelial growth factor (VEGF) show clinical benefits in treating nonsmall cell lung cancers (NSCLCs) by inhibiting tumor angiogenesis. Nonetheless, the therapeutic effects of systemically administered anti-VEGF antibodies are often hindered in NSCLCs because of their limited distribution in the lungs and their adverse effects on normal tissues. These challenges can be overcome by delivering therapeutic antibodies in their mRNA form to lung endothelial cells, a primary target of VEGF-mediated pulmonary angiogenesis, to suppress the NSCLCs. In this study, we synthesized derivatives of poly(ß-amino esters) (PBAEs) and prepared nanoparticles to encapsulate the synthetic mRNA encoding bevacizumab, an anti-VEGF antibody used in the clinic. Optimization of nanoparticle formulations resulted in a selective lung transfection after intravenous administration. Notably, the optimized PBAE nanoparticles were distributed in lung endothelial cells, resulting in the secretion of bevacizumab. We analyzed the protein corona on the lung- and spleen-targeting nanoparticles using proteomics and found distinctive features potentially contributing to their organ-selectivity. Lastly, bevacizumab mRNA delivered by the lung-targeting PBAE nanoparticles more significantly inhibited tumor proliferation and angiogenesis than recombinant bevacizumab protein in orthotopic NSCLC mouse models, supporting the therapeutic potential of bevacizumab mRNA therapy and its selective delivery through lung-targeting nanoparticles. Our proof-of-principle results highlight the clinical benefits of nanoparticle-mediated mRNA therapy in anticancer antibody treatment in preclinical models.

TonEBP/NFAT5 expression is associated with cisplatin resistance and migration in macrophage-induced A549 cells.

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.

The usefulness of lactate/albumin ratio, C-reactive protein/albumin ratio, procalcitonin/albumin ratio, SOFA, and qSOFA in predicting the prognosis of patients with sepsis who presented to EDs.

PURPOSE: Early identification of sepsis with a poor prognosis in the emergency department (ED) is crucial for prompt management and improved outcomes. This study aimed to examine the predictive value of sequential organ failure assessment (SOFA), quick SOFA (qSOFA), lactate to albumin ratio (LAR), C-reactive protein to albumin ratio (CAR), and procalcitonin to albumin ratio (PAR), obtained in the ED, as predictors for 28-day mortality in patients with sepsis and septic shock. MATERIALS AND METHODS: We included 3499 patients (aged ≥19 years) from multicenter registry of the Korean Shock Society between October 2015 and December 2019. The SOFA score, qSOFA score, and lactate level at the time of registry enrollment were used. Albumin, C-reactive protein, and procalcitonin levels were obtained from the initial laboratory results measured upon ED arrival. We evaluated the predictive accuracy for 28-day mortality using the area under the receiver operating characteristic (AUROC) curve. A multivariable logistic regression analysis of the independent predictors of 28-day mortality was performed. The SOFA score, LAR, CAR, and PAR were converted to categorical variables using Youden's index and analyzed. Adjusting for confounding factors such as age, sex, comorbidities, and infection focus, adjusted odds ratios (aOR) were calculated. RESULTS: Of the 3499 patients, 2707 (77.4%) were survivors, whereas 792 (22.6%) were non-survivors. The median age of the patients was 70 (25th-75th percentiles, 61-78), and 2042 (58.4%) were male. LAR for predicting 28-day mortality had the highest AUROC, followed by the SOFA score (0.715; 95% confidence interval (CI): 0.69-0.74 and 0.669; 95% CI: 0.65-0.69, respectively). The multivariable logistic regression analysis revealed that the aOR of LAR >1.52 was 3.75 (95% CI: 3.16-4.45), and the aOR, of SOFA score at enrollment >7.5 was 2.67 (95% CI: 2.25-3.17). CONCLUSION: The results of this study showed that LAR is a relatively strong predictor of sepsis prognosis in the ED setting, indicating its potential as a straightforward and practical prognostic factor. This finding may assist healthcare providers in the ED by providing them with tools to risk-stratify patients and predict their mortality.

Propensity score matched analysis for the safety and effectiveness of remdesivir in COVID-19 patients with renal impairment.

BACKGROUNDS: Remdesivir (RDV) is an antiviral agent approved for the treatment of coronavirus disease 2019 (COVID-19); however, is not recommended for patients with renal impairment. Due to limitations associated with prospective clinical trials, real-world data on the safety and efficacy of RDV in patients with renal impairment are necessary. METHODS: Propensity score-matched (PSM) retrospective analysis was conducted between March 2020 and September 2022 in COVID-19 patients with an eGFR < 30 mL/min in four Korean hospitals. The RDV treatment group was matched to the untreated control group. The safety and clinical outcomes in patients who received RDV were analyzed. RESULTS: A total of 564 patients were enrolled; 229 patients received RDV either for treatment or prophylaxis. On day 5, no difference in nephrotoxicity was observed between the two groups, and liver enzyme levels were within the normal range. In multivariate analysis for new dialysis, RDV treatment was not a risk factor for new dialysis. Among the 564 patients, 417 were indicated for a 5-day course of RDV treatment and 211 patients were treated with RDV. After PSM, no differences in the clinical outcomes were observed between the two groups. CONCLUSION: RDV use in COVID-19 patients with renal impairment did not result in significant nephrotoxicity or hepatotoxicity.

Health-related quality of life of pediatric brain tumor survivors after treatment in Jordan.

Background: The number of cancer survivors and survivorship are increasing. Health-related quality of life (HRQOL) has not been widely studied in low-and-middle-income countries (LMICs). The aim of this study is to explore HRQOL of childhood brain tumor survivors and its determinants in Jordan. Methods: Health-related quality of life information was collected from 80 patients treated at the King Hussein Cancer Center and their parents using the Pediatric Quality of Life Inventory (PedsQL) Generic Core Scales questionnaire in Arabic. Multivariable linear OLS regression models were used to analyze correlates of HRQOL and compare differences between child- and parent-reported responses. Results: Health-related quality of life scores reported by survivors and by parents were positively correlated on all subscales and total PedsQL scores (r = 0.59, P = .001). Survivors reported better HRQOL in cognitive subscale (ß = 0.56, P = .03) and worse HRQOL in work subscale (ß = 0.43, P = .04), but no significant differences in the physical, emotional, and social subscales and total PedsQL scores. Significant predictors of HRQOL reported by parents and by children were different. Supratentorial tumor location was associated with a 10.97-unit lower physical HRQOL score, and recurrence of tumors predicted a 17.5-unit lower total HRQOL score, indicating worse quality of life. Male gender (ß = 14.9, P = .002) and diagnosis of hypopituitarism (ß = 16.1, P = .03) were associated with better HRQOL. Furthermore, patients that only had radiotherapy treatment had better emotional HRQOL (ß = 32.9, P = .006) compared to patients that had combined radiotherapy and chemotherapy. Conclusion: This study provides evidence on determinants of HRQOL of pediatric brain tumor patients in Jordan. Future studies need to capitalize on the findings of this study to institute a system for regular assessment of quality of life of pediatric cancer patients in Jordan and other countries with similar health care systems and sociocultural backgrounds.

Bioactivity-Guided Fraction from Viscera of Abalone, Haliotis discus hannai Suppresses Cellular Basophils Activation and Anaphylaxis in Mice.

Basophils and mast cells are specialized effector cells in allergic reactions. Haliotis discus hannai (abalone), is valuable seafood. Abalone male viscera, which has a brownish color and has not been previously reported to show anti-allergic activities, was extracted with acetone. Six different acetone/hexane fractions (0, 10, 20, 30, 40, and 100%) were obtained using a silica column via ß-hexosaminidase release inhibitory activity-guided selection in phorbol myristate acetate and a calcium ionophore, A23187 (PMACI)-induced human basophils, KU812F cells. The 40% acetone/hexane fraction (A40) exhibited the strongest inhibition of PMACI-induced-ß-hexosaminidase release. This fraction dose-dependently inhibited reactive oxygen species (ROS) production and calcium mobilization without cytotoxicity. Western blot analysis revealed that A40 down-regulated PMACI-induced MAPK (ERK 1/2, p-38, and JNK) phosphorylation, and the NF-κB translocation from the cytosol to membrane. Moreover, A40 inhibited PMACI-induced interleukin (IL)-1ß, IL-6, and IL-8 production. Anti-allergic activities of A40 were confirmed based on inhibitory effects on IL-4 and tumor necrosis factor alpha (TNF-α) production in compound (com) 48/80-induced rat basophilic leukemia (RBL)-2H3 cells. A40 inhibited ß-hexosaminidase release and cytokine production such as IL-4 and TNF-α produced by com 48/80-stimulated RBL-2H3 cells. Furthermore, it's fraction attenuated the IgE/DNP-induced passive cutaneous anaphylaxis (PCA) reaction in the ears of BALB/c mice. Our results suggest that abalone contains the active fraction, A40 is a potent therapeutic and functional material to treat allergic diseases.

Shaping the "hot" immunogenic tumor microenvironment by nanoparticles co-delivering oncolytic peptide and TGF-ß1 siRNA for boosting checkpoint blockade therapy.

Induction of potent immune responses toward tumors remains challenging in cancer immunotherapy, in which it only showed benefits in a minority of patients with "hot" tumors, which possess pre-existing effector immune cells within the tumor. In this study, we proposed a nanoparticle-based strategy to fire up the "cold" tumor by upregulating the components associated with T and NK cell recruitment and activation and suppressing TGF-ß1 secretion by tumor cells. Specifically, LTX-315, a first-in-class oncolytic cationic peptide, and TGF-ß1 siRNA were co-entrapped in a polymer-lipid hybrid nanoparticle comprising PLGA, DSPE-mPEG, and DSPE-PEG-conjugated with cRGD peptide (LTX/siR-NPs). The LTX/siR-NPs showed significant inhibition of TGF-ß1 expression, induction of type I interferon release, and triggering immunogenic cell death (ICD) in treated tumor cells, indicated via the increased levels of danger molecules, an in vitro setting. The in vivo data showed that the LTX/siR-NPs could effectively protect the LTX-315 peptide from degradation in serum, which highly accumulated in tumor tissue. Consequently, the LTX/siR-NPs robustly suppressed TGF-ß1 production by tumor cells and created an immunologically active tumor with high infiltration of antitumor effector immune cells. As a result, the combination of LTX/siR-NP treatment with NKG2A checkpoint inhibitor therapy remarkably increased numbers of CD8+NKG2D+ and NK1.1+NKG2D+ within tumor masses, and importantly, inhibited the tumor growth and prolonged survival rate of treated mice. Taken together, this study suggests the potential of the LTX/siR-NPs for inflaming the "cold" tumor for potentiating the efficacy of cancer immunotherapy.

Liposomal co-delivery of toll-like receptors 3 and 7 agonists induce a hot triple-negative breast cancer immune environment.

Triple-negative breast cancer (TNBC) is highly aggressive and has no standard treatment. Although being considered as an alternative to conventional treatments for TNBC, immunotherapy has to deal with many challenges that hinder its efficacy, particularly the poor immunogenic condition of the tumor microenvironment (TME). Herein, we designed a liposomal nanoparticle (LN) platform that delivers simultaneously toll-like receptor 7 (imiquimod, IQ) and toll-like receptor 3 (poly(I:C), IC) agonists to take advantage of the different toll-like receptor (TLR) signaling pathways, which enhances the condition of TME from a "cold" to a "hot" immunogenic state. The optimized IQ/IC-loaded LN (IQ/IC-LN) was effectively internalized by cancer cells, macrophages, and dendritic cells, followed by the release of the delivered drugs and subsequent stimulation of the TLR3 and TLR7 signaling pathways. This stimulation encouraged the secretion of type I interferon (IFN-α, IFN-ß) and CXCLl0, a T-cell and antigen-presenting cells (APCs) recruitment chemokine, from both cancer cells and macrophages and polarized macrophages to the M1 subtype in in vitro studies. Notably, systemic administration of IQ/IC-LN allowed for the high accumulation of drug content in the tumor, followed by the effective uptake by immune cells in the TME. IQ/IC-LN treatment comprehensively enhanced the immunogenic condition in the TME, which robustly inhibited tumor growth in tumor-bearing mice. Furthermore, synergistic antitumor efficacy was obtained when the IQ/IC-LN-induced immunogenic state in TME was combined with anti-PD1 antibody therapy. Thus, our results suggest the potential of combining 2 TLR agonists to reform the TME from a "cold" to a "hot" state, supporting the therapeutic efficacy of immune checkpoint inhibitors.

Macrophage-reprogramming upconverting nanoparticles for enhanced TAM-mediated antitumor therapy of hypoxic breast cancer.

In an attempt to achieve antitumor effects by switching the phenotype of macrophages from the tumor-promoting M2 type to the tumor-suppressing M1 type, we fabricated mannose-decorated/macrophage membrane-coated, silica-layered NaErF4@NaLuF4 upconverting nanoparticles (UCNPs) co-doped with perfluorocarbon (PFC)/chlorin e6 (Ce6) and loaded with paclitaxel (PTX) (UCNP@mSiO2-PFC/Ce6@RAW-Man/PTX: ∼61 nm; -11.6 mV). These nanoparticles were designed to have two major functionalities, (i) efficient singlet oxygen generation aided by an oxygen supply and (ii) good targeting to tumor-associated macrophage (TAMs) (M2-type), to induce polarization to M1 type macrophages that release proinflammatory cytokines and suppress breast cancers. The primary UCNPs consisted of lanthanide elements (erbium and lutetium) in a core@shell structure, and they facilely emitted 660 nm light in response to a deep-penetrating 808 nm near-infrared laser. Moreover, the UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX were able to release O2 and generate 1O2 because of the co-doped PFC/Ce6 and upconversion. Our nanocarriers' excellent uptake to RAW 264.7 macrophage cells (M2 type) and efficient M1-type polarization activity were clearly demonstrated using qRT-PCR and immunofluorescence-based confocal laser scanning microscopy. Our nanocarriers displayed significant cytotoxicity to 4T1 cells in 2D culture and 3D co-culture systems of 4T1/RAW 264.7 cells. More importantly, UCNPs@mSiO2-PFC/Ce6@RAW-Man/PTX (+808 nm laser) noticeably suppressed tumor growth in 4T1-xenografted mice, compared with the other treatment groups (332.4 vs. 709.5-1185.5 mm3). We attribute this antitumor efficacy to the prominent M1-type macrophage polarization caused by our nanocarriers through efficient ROS/O2 generation and targeting of M2-type TAMs via mannose ligands on coated macrophage-membrane.

Nutrition Therapy by Nutrition Support Team: A Comparison of Multi-Chamber Bag and Customized Parenteral Nutrition in Hospitalized Patients.

This study aimed to investigate the activity of a nutrition support team (NST) and the trends of multi-chamber bag (MCB) and customized parenteral nutrition (PN) with NST consultations in South Korea. Data were obtained from the National Inpatient Sample Cohort between 2015 and 2020. Three datasets were constructed for NST consultation, MCB-PN product prescriptions, and aseptic preparation of total PN. The intersections of the NST consultation and each PN dataset were compiled into MCB-PN with NST or customized PN with a NST sub-dataset, respectively. Using personal identifiers, the patients' characteristics were evaluated in the NST cohort. A total of 91,384 reimbursements and 70,665 patients were included. The NST activity had increased by more than 50% over 6 years. Approximately 70% and 11%, respectively, of the NST cohort were classified into two subgroups: MCB-PN with NST (M-NST) and customized PN with NST (C-NST). M-NST had many elderly patients with cancer and showed a higher in-hospital mortality than C-NST (12.6% vs. 9.5%). C-NST included a larger number of patients under the age of 5 years, and the hospitalization period was more extended than M-NST (26.2 vs. 21.2 days). The present study showed that NST activities and the proportion of PN with NST consultation are gradually increasing in South Korea.

Suction Drain Tip Cultures in Predicting a Surgical Site Infection.

STUDY DESIGN: Retrospective study. PURPOSE: This study aimed to evaluate the prognostic value of drain tip culture after spinal surgery with a large number of participants. OVERVIEW OF LITERATURE: The routine culture of suction drain tips that are placed in the surgical site of spinal surgeries has been performed in many institutions to detect surgical site infection (SSI). However, few reports have evaluated drain tip culture as a prognostic for SSI after spinal surgery. Materials and. METHODS: This study retrospectively included 1,415 consecutive patients who underwent spinal surgery between January 2016 and December 2021. Patients diagnosed with infectious diseases were excluded. Prophylactic antibiotics were administered intraoperatively and 24 hours postoperatively. Drains were removed when the volume of postoperative fluid drainage was <50 mL and <100 mL in patients who underwent cervical and thoracic surgery and lumbar surgery in the preceding 24 hours, respectively, and cultures were made. We evaluated the correlation between the results of positive drain tip culture and SSI. RESULTS: Positive drain tip cultures were found in 51 cases (3.6%). SSI was identified in 34 cases (2.4%). The most frequently isolated microorganism was methicillin-resistant Staphylococcus epidermidis (61.8%). The sensitivity, specificity, and positive, and negative predictive values of drain tip culture were 50.0%, 97.4%, 32.1%, and 98.8%, respectively. The same bacteria were isolated from the surgical lesion in 16 of 17 SSI cases with a positive drain tip culture, thereby giving a bacteria matching rate between tissue culture and drain tip culture of 94.1%. The number of surgery levels, drain remaining period, and drain tip culture positivity were significantly increased in the SSI group. CONCLUSIONS: Drain tip cultures might be useful for predicting SSI. Drain tip culture had a high positivity rate in the SSI group, and the coincidence rate for the causative pathogen was high.

Development of a sorafenib-loaded solid self-nanoemulsifying drug delivery system: Formulation optimization and characterization of enhanced properties.

Sorafenib, marketed under the brand name Nexavar®, is a multiple tyrosine kinase inhibitor drug that has been actively used in the clinical setting for the treatment of several cancers. However, the low solubility and bioavailability of sorafenib constitute a significant barrier to achieving a good therapeutic outcome. We developed a sorafenib-loaded self-nanoemulsifying drug delivery system (SNEDDS) formulation composed of capmul MCM, tween 80, and tetraglycol, and demonstrated that the SNEDDS formulation could improve drug solubility with excellent self-emulsification ability. Moreover, the sorafenib-loaded SNEDDS exhibited anticancer activity against Hep3B and KB cells, which are the most commonly used hepatocellular carcinoma and oral cancer cell lines, respectively. Subsequently, to improve the storage stability and to increase the possibility of commercialization, a solid SNEDDS for sorafenib was further developed through the spray drying method using Aerosil® 200 and PVP K 30. X-ray diffraction and differential scanning calorimeter data showed that the crystallinity of the drug was markedly reduced, and the dissolution rate of the drug was further improved in formulation in simulated gastric and intestinal fluid conditions. In vivo study, the bioavailability of the orally administered formulation increases dramatically compared to the free drug. Our results highlight the use of the solid-SNEDDS formulation to enhance sorafenib's bioavailability and outlines potential translational directions for oral drug development.

Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug.

Introduction: Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Methods: Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. Results: When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Discussion: Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.

A detailed insight of the tumor targeting using nanocarrier drug delivery system.

Human struggle against the deadly disease conditions is continued since ages. The contribution of science and technology in fighting against these diseases cannot be ignored exclusively due to the invention of novel procedure and products, extending their size ranges from micro to nano. Recently nanotechnology has been gaining more consideration for its ability to diagnose and treat different cancers. Different nanoparticles have been used to evade the issues related with conservative anticancer delivery systems, including their nonspecificity, adverse effects and burst release. These nanocarriers including, solid lipid nanoparticles (SLNs), liposomes, nano lipid carriers (NLCs), nano micelles, nanocomposites, polymeric and magnetic nanocarriers, have brought revolutions in antitumor drug delivery. Nanocarriers improved the therapeutic efficacy of anticancer drugs with better accumulation at the specific site with sustained release, improved bioavailability and apoptosis of the cancer cells while bypassing the normal cells. In this review, the cancer targeting techniques and surface modification on nanoparticles are discussed briefly with possible challenges and opportunities. It can be concluded that understanding the role of nanomedicine in tumor treatment is significant, and therefore, the modern progressions in this arena is essential to be considered for a prosperous today and an affluent future of tumor patients.

Amplified Fenton-Based Oxidative Stress Utilizing Ultraviolet Upconversion Luminescence-Fueled Nanoreactors for Apoptosis-Strengthened Ferroptosis Anticancer Therapy.

As an emerging anticancer strategy, ferroptosis has recently been developed in combination with current therapeutic modalities to overcome the existing limitations of conventional therapies. Herein, an ultraviolet (UV) upconversion luminescence-fueled nanoreactor is explored to combine ferroptosis and apoptosis through the UV-catalyzed Fenton reaction of an iron supplement (ferric ammonium citrate) loaded in a mesoporous silica layer in addition to the support of a chemotherapeutic agent (cisplatin) attached on the functionalized silica surface for the treatment of triple negative breast cancer (TNBC). The nanoplatform can circumvent the low penetration depth typical of UV light by upconverting near-infrared irradiation and emitting UV photons that convert Fe3+ to Fe2+ to boost the generation of hydroxyl radicals (·OH), causing devastating lipid peroxidation. Apart from DNA damage-induced apoptosis, cisplatin can also catalyze Fenton-based therapy by its abundant production of hydrogen peroxide (H2O2). As a bioinspired lipid membrane, the folate receptor-targeted liposome as the coating layer offers high biocompatibility and colloidal stability for the upconversion nanoparticles, in addition to prevention of the premature release of encapsulated hydrophilic compounds, before driving the nanoformulation to the target tumor site. As a result, superior antitumor efficacy has been observed in a 4T1 tumor-bearing mouse model with negligible side effects, suggesting that such a nanoformulation could play a pivotal role in effective apoptosis-strengthened ferroptosis TNBC therapy.

Public awareness of chronic venous disease in Korea.

OBJECTIVE: This study aimed to evaluate the current level of chronic venous disease (CVD) awareness and its relevant influencing factors. METHODS: Online and interview surveys were conducted in two distinct groups from May 14 to June 16, 2020. An online survey was conducted among 900 adults aged 20 to 64 years from the research database, whereas interviews were conducted among 124 patients who presented with CVD symptoms, which covered the awareness of such symptoms and their impact on quality of life. RESULTS: Most respondents reported low levels of CVD awareness by recognizing the disease only by an entity. In 53 respondents who visited the hospital with suspected venous symptoms, the actual diagnosis was made in only 30.2%. CVD diagnosis was associated with increased CVD awareness. Female sex, age of >29 years, higher educational level, and higher income were associated with increased CVD awareness. Approximately 60% of the patients with CVD responded that physical symptoms had a negative impact on their quality of life rather than emotion or appearance. CONCLUSIONS: The public is largely unaware of CVD but not in detail. Educational programs to improve CVD awareness should be implemented to enable appropriate CVD management.

Is there any benefit in the combined ligament reconstruction with osteotomy compared to ligament reconstruction or osteotomy alone?: Comparative outcome analysis according to the degree of medial compartment osteoarthritis with anterior or posterior cruciate ligament insufficiency.

INTRODUCTION: The purpose of this study was to compare the outcomes of middle-aged patients with anterior cruciate ligament (ACL) or posterior cruciate ligament (PCL) insufficiency by assessing different groups: high tibial osteotomy (HTO), HTO with combined ligament reconstruction, and isolated ligament reconstruction according to the alignment change and medial compartment osteoarthritis (OA). MATERIALS AND METHODS: From 2014 to 2019, middle-aged (40-65 years) patients with knee instability were enrolled in this retrospective study. They were categorized into three groups: group I, HTO; group II, HTO with combined ACL or PCL reconstruction; and group III, isolated ligament reconstruction. Radiological outcomes, including Kellgren-Lawrence grade, mechanical femorotibial angle (mFTA), weight-bearing line (WBL) ratio, and posterior tibial slope were compared. Knee stability and clinical outcomes were also compared. RESULTS: Seventy-nine patients completed the final assessment. Group I was older than other two groups (p = 0.006). Groups I and II had a higher body mass index (p = 0.043) and more preoperative varus alignment than group III (p < 0.001). OA severity was ranked in the order of group I, II, and III (p < 0.001). Group I showed more valgus alignment than group II after HTO (p = 0.024 for mFTA and 0.044 for WBL ratio, respectively). Compared to their preoperative status, all three groups showed significant improvement in knee stability (p < 0.001); however, group I showed inferior knee stability regardless of ACL or PCL reconstruction (p < 0.001 and 0.043, respectively). All clinical scores significantly improved in the three groups (p < 0.001), and they showed comparable clinical outcomes in the final assessment. CONCLUSIONS: Our strategy in managing middle-aged patients with knee instability according to the varus alignment and medial degeneration showed favorable stability and clinical outcomes. Middle-aged patients with knee instability should be managed with different strategies depending on their status. LEVEL OF EVIDENCE: Case-control study; Level-III.

Development of a machine learning model to predict lateral hinge fractures by analyzing patient factors before open wedge high tibial osteotomy.

PURPOSE: Several methods have been developed to prevent lateral hinge fractures (LHFs), using only classic statistical models. Machine learning is under the spotlight because of its ability to analyze various weights and model nonlinear relationships. The purpose of this study was to create a machine learning model that predicts LHF with high predictive performance. METHODS: Data were collected from a total of 439 knees with medial osteoarthritis (OA) treated with Medial open wedge high tibial osteotomy (MOW-HTO) from March 2014 to February 2020. The patient data included age, sex, height, and weight. Preoperative, determined, and modifiable factors were categorized using X-ray and CT data to create ensemble models with better predictive performance. Among the 57 ensemble models, which is the total number of possible combinations with six models, the model with the highest area under curve (AUC) or F1-score was selected as the final ensemble model. Gain feature importance analysis and the Shapley additive explanations (SHAP) feature explanation were performed on the best models. RESULTS: The ensemble model with the highest AUC was a combination of a light gradient boosting machine (LGBM) and multilayer perceptron (MLP) (AUC = 0.992). The ensemble model with the highest F1-score was the model that combined logistic regression (LR) and MLP (F1-score = 0.765). Distance X was the most predictive feature in the results of both model interpretation analyses. CONCLUSION: Two types of ensemble models, LGBM with MLP and LR with MLP, were developed as machine learning models to predict LHF with high predictive performance. Using these models, surgeons can identify important features to prevent LHF and establish strategies by adjusting modifiable factors. STUDY DESIGN: Retrospective cohort study.

Survival benefit of direct transport to trauma centers among patients with unintentional injuries in Korea: a propensity score-matched analysis.

OBJECTIVE: This study investigated the characteristics and survival rates of patients with unintentional severe trauma who visited a regional trauma center (TC) or a non-TC. METHODS: This retrospective, national, population-based, observational, case-control study included patients with abnormal Revised Trauma Score from January 2018 to December 2018. We divided hospitals into two types, TC and non-TC, and compared several variables, including in-hospital mortality. Propensity score matching was used to reduce the effect of confounding variables that influence survival outcome variables. RESULTS: Of the 25,743 patients, 5,796 visited a TC and 19,947 visited a non-TC. Compared to patients treated at non-TCs, patients treated at TCs were more likely to have a higher Injury Severity Score (TC, 11.5; non-TC, 7.4; P<0.001), higher rate of surgery or transcatheter arterial embolization (TC, 39.2%; non-TC, 17.6%; P<0.001), and higher admission rate (TC, 64.7%; non-TC, 36.9%; P<0.001) through the emergency department. After propensity score matching, 2,800 patients from both groups were analyzed. Patients in the TC had a higher survival rate than patients that were not treated in the TC (TC, 83.0%; non-TC, 78.6%; P=0.003). CONCLUSION: This study using Korean emergency medical services data showed that initial transport to trauma centers was associated with mortality reduction. Further research is required because of limitations with use of single-year data and retrospective design.