Genome-wide methylation profiling reveals extracellular vesicle DNA as an ex vivo surrogate of cancer cell-derived DNA.

Extracellular vesicle-derived DNA (evDNA) encapsulates the complete genome and mutational status of cells; however, whether cancer cell-derived evDNA mirrors the epigenetic features of parental genomic DNA remains uncertain. This study aimed to assess and compare the DNA methylation patterns of evDNA from cancer cell lines and primary cancer tissues with those of the nuclear genomic DNA. We isolated evDNA secreted by two cancer cell lines (HCT116 and MDA-MB-231) from various subcellular compartments, including the nucleus and cytoplasm. Additionally, we obtained evDNA and nuclear DNA (nDNA) from the primary cancer tissues of colon cancer patients. We conducted a comprehensive genome-wide DNA methylation analysis using the Infinium Methylation EPIC BeadChip, examining > 850,000 CpG sites. Remarkable similarities were observed between evDNA and nDNA methylation patterns in cancer cell lines and patients. This concordance extended to clinical cancer tissue samples, showcasing the potential utility of evDNA methylation patterns in deducing cellular origin within heterogeneous populations through methylation-based deconvolution. The observed concordance underscores the potential of evDNA as a noninvasive surrogate marker for discerning tissue origin, particularly in cancer tissues, offering a promising future for cancer diagnostics. This finding enhances our understanding of cellular origins and would help develop innovative diagnostic and therapeutic strategies for cancer.

Genetic analyses of Anisakis pegreffii (Nematoda: Anisakidae) from the East Asian finless porpoise Neophocaena asiaeorientalis sunameri (Cetacea: Phocoenidae) in Korean waters.

The East Asian finless porpoise, Neophocaena asiaeorientalis sunameri, is an endangered species that inhabits the coastal marine environments of East Asia. In the present study, we investigated the overall infection status of anisakid nematodes in East Asian finless porpoises from three sea sectors off the Korean Peninsula. The genetic diversity and population genetic structure of the identified nematode species were evaluated. The prevalence of all stages of anisakid nematodes collected from the stomach was 57.55% (61 among the 106 porpoises examined), and 16 of the hosts were found to have adult worms. The mean number of infected adults was 211 (± 419.54, 5-1455 per host). Only one species of anisakids, Anisakis pegreffii, was identified from randomly selected worms by molecular approaches. Analysis of the mitochondrial (mt) cox2 partial gene in 50 newly generated sequences of A. pegreffii revealed 24 haplotypes, including 14 new haplotypes. We observed below-average levels of nucleotide diversity and haplotype diversity compared to other seas around the world. The mtDNA cox2 haplotypes of the species in the three Korean sea areas showed no genetic structure, suggesting well-connected gene flow within these areas. This study represents the first record of a definitive host of A. pegreffii in Korean waters, providing important information regarding anisakids genetic diversity in the cetacean species inhabiting limited regions.

Coating Robust Layers on Ni-Rich Cathode Active Materials while Suppressing Cation Mixing for All-Solid-State Lithium-Ion Batteries.

This study focused on addressing the challenges associated with the incompatibility between sulfide solid electrolytes and Ni-rich cathode active materials (CAMs) in all-solid-state lithium-ion batteries. To resolve these issues, protective layers have been explored for Ni-rich materials. Lithium lanthanum titanate (LLTO), a perovskite-type material, is recognized for its excellent chemical stability and ionic conductivity, which render it a potential protective layer in CAMs. However, traditional methods of achieving the perovskite structure involve temperatures exceeding 700 °C, resulting in challenges such as LLTO agglomeration, secondary phase formation between LLTO and CAM, and cation mixing within the CAM. In this study, a rapid technique known as flash-light sintering (FLS) was employed to fabricate a uniform and pure perovskite protective layer without inducing cation mixing within the CAM. The LLTO-coated LiNi0.8Co0.1Mn0.1O2 (NCM811) with FLS treatment demonstrated minimal cation mixing and formed a fully covered dense layer. This resulted in a high initial capacity and effectively addressed the incompatibility issues between the sulfide electrolytes and CAM. The rapid FLS method not only streamlines the fabrication of LLTO-coated NCM811 but also provides opportunities for its broader application to materials that were previously deemed impractical because of high sintering temperatures.

Evolutionary dependency of cancer mutations in gene pairs inferred by nonsynonymous-synonymous mutation ratios.

BACKGROUND: Determining the impact of somatic mutations requires understanding the functional relationship of genes acquiring mutations; however, it is largely unknown how mutations in functionally related genes influence each other. METHODS: We employed non-synonymous-to-synonymous or dNdS ratios to evaluate the evolutionary dependency (ED) of gene pairs, assuming a mutation in one gene of a gene pair can affect the evolutionary fitness of mutations in its partner genes as mutation context. We employed PanCancer- and tumor type-specific mutational profiles to infer the ED of gene pairs and evaluated their biological relevance with respect to gene dependency and drug sensitivity. RESULTS: We propose that dNdS ratios of gene pairs and their derived cdNS (context-dependent dNdS) scores as measure of ED distinguishing gene pairs either as synergistic (SYN) or antagonistic (ANT). Mutation contexts can induce substantial changes in the evolutionary fitness of mutations in the paired genes, e.g., IDH1 and IDH2 mutation contexts lead to substantial increase and decrease of dNdS ratios of ATRX indels and IDH1 missense mutations corresponding to SYN and ANT relationship with positive and negative cdNS scores, respectively. The impact of gene silencing or knock-outs on cell viability (genetic dependencies) often depends on ED, suggesting that ED can guide the selection of candidates for synthetic lethality such as TCF7L2-KRAS mutations. Using cell line-based drug sensitivity data, the effects of targeted agents on cell lines are often associated with mutations of genes exhibiting ED with the target genes, informing drug sensitizing or resistant mutations for targeted inhibitors, e.g., PRSS1 and CTCF mutations as resistant mutations to EGFR and BRAF inhibitors for lung adenocarcinomas and melanomas, respectively. CONCLUSIONS: We propose that the ED of gene pairs evaluated by dNdS ratios can advance our understanding of the functional relationship of genes with potential biological and clinical implications.

A Subset of Microsatellite Unstable Cancer Genomes Prone to Short Insertions over Deletions Is Associated with Elevated Anticancer Immunity.

Deficiencies in DNA mismatch repair (MMRd) leave characteristic footprints of microsatellite instability (MSI) in cancer genomes. We used data from the Cancer Genome Atlas and International Cancer Genome Consortium to conduct a comprehensive analysis of MSI-associated cancers, focusing on indel mutational signatures. We classified MSI-high genomes into two subtypes based on their indel profiles: deletion-dominant (MMRd-del) and insertion-dominant (MMRd-ins). Compared with MMRd-del genomes, MMRd-ins genomes exhibit distinct mutational and transcriptomic features, including a higher prevalence of T>C substitutions and related mutation signatures. Short insertions and deletions in MMRd-ins and MMRd-del genomes target different sets of genes, resulting in distinct indel profiles between the two subtypes. In addition, indels in the MMRd-ins genomes are enriched with subclonal alterations that provide clues about a distinct evolutionary relationship between the MMRd-ins and MMRd-del genomes. Notably, the transcriptome analysis indicated that MMRd-ins cancers upregulate immune-related genes, show a high level of immune cell infiltration, and display an elevated neoantigen burden. The genomic and transcriptomic distinctions between the two types of MMRd genomes highlight the heterogeneity of genetic mechanisms and resulting genomic footprints and transcriptomic changes in cancers, which has potential clinical implications.

Effect duration of lumbar sympathetic ganglion neurolysis in patients with complex regional pain syndrome: a prospective observational study.

Lumbar sympathetic ganglion neurolysis (LSGN) has been used for long-term pain relief in patients with complex regional pain syndrome (CRPS). However, the actual effect duration of LSGN has not been accurately measured. This prospective observational study measured the effect duration of LSGN in CRPS patients and investigated the relationship between temperature change and pain relief. After performing LSGN, the skin temperatures of both the maximum pain site and the plantar area in the affected and unaffected limbs were measured by infrared thermography, and pain intensity was assessed before and at 2 weeks, 1 month, and 3 months. The median time to return to baseline temperature was calculated using survival analysis. The skin temperature increased significantly at all-time points relative to baseline in both regions (maximum pain site: 1.4 °C ± 1.0 °C, plantar region: 1.28 °C ± 0.8 °C, all P < 0.001). The median time to return to baseline temperature was 12 weeks (95% confidence interval [CI] 7.7-16.3) at the maximum pain site and 12 weeks (95% CI 9.4-14.6) at the plantar area. Pain intensity decreased significantly relative to baseline, at all-time points after LSGN. In conclusion, the median duration of the LSGN is estimated to be 12 weeks.

Analysis of the efficacy of retrodiscal approach percutaneous epidural adhesiolysis with WHIP catheter® in patients with lumbar radiculopathy: A retrospective study.

Percutaneous epidural adhesiolysis (PEA) is an effective treatment for patients with lumbar radiculopathy unresponsive to single steroid injections. Various approaches and instruments have been developed to access these lesions. This study aimed to evaluate the utility of a retrodiscal approach for epidural adhesiolysis using a WHIP catheter®. This retrospective study was conducted at Bundang Seoul National University Hospital, reviewing cases from January to December 2022. Forty-seven patients diagnosed with lumbar radiculopathy, aged 20 to 80 years, who underwent PEA with the WHIP catheter® were included. Outcomes assessed Numeric Rating Scale (NRS) for pain, Patients' Global Impression of Change (PGIC) scores, and the incidence of procedure-related complications. Follow-up evaluations occurred at 1, 3, and 6 months post-procedure. Among 47 patients, 41 completed the study, showing significant pain reduction at all follow-up points: 1 month (N = 41, 1.32 ±â€…1.68, P < .001), 3 months (N = 31, 1.90 ±â€…2.14, P < .001), and 6 months (N = 30, 2.50 ±â€…2.30, P < .001). PGIC scores indicated that 40% of the patients reported substantial improvement at one-month post-procedure. The complications were minimal, with only one case of intradiscal injection and 2 cases of vascular uptake. The retrodiscal approach PEA using the WHIP catheter® demonstrated significant efficacy in pain reduction with minimal safety concerns for patients with lumbar radiculopathy. These findings suggest that this procedure is a viable option for patients who are unresponsive to conservative treatment. However, the retrospective nature of this study and its small sample size necessitate further prospective controlled studies to confirm our results and establish long-term outcomes.

Ingestion of fishing gear and Anisakis sp. infection in a beached Indo-Pacific finless porpoise (Neophocaena phocaenoides) in the Jeju Island, Republic of Korea: findings from post-mortem computed tomography and necropsy.

BACKGROUND: Human fishing activities have significantly affect environmental concern for marine ecosystems, conservation of marine mammals, and human health. Coastal cetaceans are highly vulnerable to ingestion of fishing gear, bycatching, or entanglement, all of which can be fatal for these animals. In particular, certain coastal dolphins and porpoises are heavily impacted by fishing gear such as angling gear or stownet, as their food often overlap with the target fish species of human fisheries. CASE PRESENTATION: This study presents a case of an Indo-Pacific finless porpoise (Neophocaena phocaenoides) beached on the coast of Jeju Island, Republic of Korea, with ingestion of fishing gear and severe Anisakis infection. Although this species inhabits waters ranging from the Persian Gulf to Taiwan, several stranded carcasses have been reported on Jeju Island in recent years. Post-mortem computed tomography revealed a bundle of four fishing hooks in the forestomach, along with nylon lines and steel lines with connectors, which were assumed to be angling gear for Jeju hairtail (Trichiurus lepturus). Further necroscopic investigation revealed that the forestomach contained a large number of Anisakis spp. (Nematoda: Anisakidae). Histological examination revealed a thickened forestomach wall with pinpoint and volcanic ulcerations, a thickened layer of stratified squamous epithelium, and infiltrated stroma in the squamous epithelium. CONCLUSIONS: This study emphasizes the urgent need to address the impact of fishing activities on marine mammals, marine litter pollution, and the bycatch problem in Korean seawater. In addition, the occurrence of N. phocaenoides in seawater around Jeju Island should be raised in future geographical ecology or veterinary pathology studies and when its distribution is updated.

Cellular abundance-based prognostic model associated with deregulated gene expression of leukemic stem cells in acute myeloid leukemia.

Background: Previous studies have reported that genes highly expressed in leukemic stem cells (LSC) may dictate the survival probability of patients and expression-based cellular deconvolution may be informative in forecasting prognosis. However, whether the prognosis of acute myeloid leukemia (AML) can be predicted using gene expression and deconvoluted cellular abundances is debatable. Methods: Nine different cell-type abundances of a training set composed of the AML samples of 422 patients, were used to build a model for predicting prognosis by least absolute shrinkage and selection operator Cox regression. This model was validated in two different validation sets, TCGA-LAML and Beat AML (n = 179 and 451, respectively). Results: We introduce a new prognosis predicting model for AML called the LSC activity (LSCA) score, which incorporates the abundance of 5 cell types, granulocyte-monocyte progenitors, common myeloid progenitors, CD45RA + cells, megakaryocyte-erythrocyte progenitors, and multipotent progenitors. Overall survival probabilities between the high and low LSCA score groups were significantly different in TCGA-LAML and Beat AML cohorts (log-rank p-value = 3.3×10-4 and 4.3×10-3, respectively). Also, multivariate Cox regression analysis on these two validation sets shows that LSCA score is independent prognostic factor when considering age, sex, and cytogenetic risk (hazard ratio, HR = 2.17; 95% CI 1.40-3.34; p < 0.001 and HR = 1.20; 95% CI 1.02-1.43; p < 0.03, respectively). The performance of the LSCA score was comparable to other prognostic models, LSC17, APS, and CTC scores, as indicated by the area under the curve. Gene set variation analysis with six LSC-related functional gene sets indicated that high and low LSCA scores are associated with upregulated and downregulated genes in LSCs. Conclusion: We have developed a new prognosis prediction scoring system for AML patients, the LSCA score, which uses deconvoluted cell-type abundance only.

Lipid emulsion treatment for local anesthetic systemic toxicity in pediatric patients: A systematic review.

BACKGROUND: Local anesthetic systemic toxicity (LAST) is rare, but fatal; the current widely used treatment is lipid emulsion (LE). The goal of this study was to analyze and review case reports on LE treatment for LAST in pediatric patients. METHODS: We performed a systematic review using case reports on LE treatment for LAST in pediatric patients, searching PubMed and Scopus databases to March 2023 using the following keywords: ("local anesthetic toxicity" OR "local anesthetic systemic toxicity" OR LAST") AND ("newborn" OR "infant" OR "child" OR "children" OR "adolescent" OR "pediatric") AND ("lipid emulsion" OR "Intralipid"). RESULTS: Our search yielded 21 cases, revealing that nearly 43% patients with LAST were less than 1 year old, and most cases were caused by bupivacaine (approximately 67% cases). "Inadvertent intravascular injection" by anesthesiologists and "overdose of local anesthetics" mainly by surgeons were responsible for 52% and 24% cases of LAST, respectively. LAST occurred in the awake state (52%) and under general anesthesia (48%), mainly causing seizures and arrhythmia, respectively. Approximately 55% of patients received LE treatment in <10 minutes after LAST, mainly improving cardiovascular symptoms. A 20% LE (1.5 mL/kg) dose followed by 0.25 mL/kg/minutes dose was frequently used. LE and anticonvulsants were mainly used in the awake state, whereas LE with or without vasopressors was mainly used under general anesthesia. LE treatment led to full recovery from LAST in 20 cases; however, 1 patient died due to underlying disease. CONCLUSION: Consequently, our findings reveal that LE is effective in treating pediatric LAST.

Oral/taste sensitivity to non-esterified long-chain fatty acids with varying degrees of unsaturation.

Understanding human oral/taste sensitivity to long-chain non-esterified fatty acids (NEFA) with varying physicochemical properties is essential to reducing the intake of fats and altering the intake composition. This study investigated the differences in human taste sensitivity to two NEFA: oleic acid and linoleic acid. Twenty-four female subjects were divided into two equal sensitivity groups, and they performed discrimination tests for both fatty acids against bottled water using either the triangle or the DR A-Not A test. To achieve an accurate measurement of NEFA sensitivity, the stimulus was carefully prepared, avoiding additives that could interfere with the binding of fatty acids to receptors. Stimuli concentrations were selected to be within the lowest range (9.9 to 177.3 µM) evaluated in previous research. Through a systematic stimulus control process, this study confirmed that greater sensitivity was exhibited to linoleic acid than oleic acid, resulting in better discrimination than previous studies.

Dyslipidemia Is Positively Associated with Chronic Low Back Pain in Korean Women: Korean National Health and Nutrition Examination Survey 2010-2012.

BACKGROUND: This study aimed to evaluate the association between chronic low back pain (CLBP) and chronic diseases, such as hypertension, diabetes, and dyslipidemia. METHODS: This study was a retrospective analysis using data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2010-2012 and included women who answered a questionnaire in the KNHANES asking whether they had low back pain for ≥3 months. Participants were divided into non-CLBP and CLBP groups. For statistical analysis, the Student's t-test, chi-square test, Fisher's exact test, and logistic regression analysis were performed using SPSS. RESULTS: Of 5961 participants, the non-CLBP group comprised 4098 women and the CLBP group comprised 1863. Adjusted logistic regression model revealed that dyslipidemia was positively associated with CLBP (odds ratio, 1.32; 95% confidence interval, 1.140, 1.530; p < 0.001). However, hypertension and diabetes were not associated with CLBP. CONCLUSIONS: Our results suggest that proper treatment of dyslipidemia may contribute to lowering the risk of CLBP later in life.

Adhesive Bowel Obstruction (ABO) in a Stranded Narrow-Ridged Finless Porpoise (Neophocaena asiaeorientalis sunameri).

In this case report, we present a rare occurrence of a narrow-ridged finless porpoise (Neophocaena asiaeorientalis sunameri), discovered on the coast of Jeju Island, Republic of Korea, that was afflicted with adhesive bowel obstruction (ABO), a life-threatening condition that has scarcely been reported in cetaceans. Diagnosis of ABO was confirmed via radiological and clinical assessments. Post-mortem computed tomography and necropsy revealed ABO between two loops of the jejunum at the L8 level. The mesenteric tissue covering the intestinal lesion was severely thickened with increased tension. Both bowel loops were fixed to the mesentery and acutely angulated, leading to asymmetrical thickening of the cross-sectional bowel walls. The intestinal lumen was stenosed because of pressure from the firm mesenteric band, and no fecal matter was observed in the lumen of the posterior bowel or rectum. Calcified nodules were detected, and histological analysis suggested parasitic or suspected post-parasitic infections. The primary cause of the intestinal lesions is presumed to be a reaction related to parasitic infection. However, further investigations would establish a definitive link between parasitic infections and ABO in this species. This case highlights the importance of studying rare medical conditions in wildlife, providing valuable insights into marine mammal health.

Characterization of Spheno-occipital Synchondrosis Fusion From Preadolescents to Young Adults Using Age and Cervical Vertebrae Maturation Index.

The purpose of this study was to characterize the spheno-occipital synchondrosis fusion (SOSF) from preadolescents to young adults. A total of 630 Korean subjects (308 men, 322 women; age range, 6-18 y) were divided into 26 groups according to sex and age. After 3-dimensional computed tomography (CT) images were reoriented using the Frankfort horizontal (FH) plane, mid-sagittal plane, and frontal plane via ON3D software (3DONS), the cervical vertebrae maturation index (CVMI) and SOSF stages were identified using 6-stage and 5-stage scoring systems, respectively. The distributions of stage in each group were statistically investigated. Women showed early appearance and a short range of onset (CVMI stage 2, SOSF stage 2), middle (CVMI stage 4, SOSF stage 3 and stage 4), and completion (CVMI stage 6, SOSF stage 5), indicating rapid skeletal maturation compared with men. In both males and females, there were strong positive correlations between age and CVMI stage (rs=0.902, rs=0.890), between age and SOSF stage (rs=0.887, rs=0.885), and between CVMI and SOSF stages (rs=0.955, rs=0.964) (all P<0.001). The mean ages at SOSF stage 3 and stage 4 (12.7~13.9 y in males and 11.0~12.5 y in females) could be used as indicators of the pubertal growth peak. Regression equations for SOSF stage (y), age (a), and CVMI stage (b) were as follows: y=1.355-(0.133×a)+(0.29007×b)+(0.041×a×b) for males (r2=0.9496); y=1.305-(0.158×a)+(0.455×b)+(0.036×a×b) for females (r2=0.9606). Ordinal logistic regression analyses with the proportional odds model showed that females had more advanced SOSF stages than males (odds ratio: 1.972; 95% CI: 1.063-3.658, P<0.05). Our findings may provide basic references for CVMI and SOSF from preadolescents to young adults.

Phylogenetic and phylogeographic analyses of Anisakis simplex sensu stricto (Nematoda: Anisakidae) from the common minke whale in Korean waters.

The genus Anisakis is among the most significant parasites to public health, as it causes anisakiasis, a parasitic infection in humans resulting from consuming raw or undercooked seafood. Although the infection status of i>Anisakis in second intermediate hosts, such as marine fishes and cephalopods, and humans have been severally reported in Korea, no information about the definitive host in Korean waters is available. In 2014, 2 adult gastric nematodes were collected from a common minke whale (Balaenoptera acutorostrata) found in the East Sea, Korea. These worms were identified as A. simplex sensu stricto (s.s.) by comparing the mitochondrial COX2 marker with previously deposited sequences. Phylogenetic and phylogeographic analyses of A. simplex (s.s.) worldwide revealed 2 distinct populations: the Pacific population and the European waters population. This is the first report on adult i>Anisakis and its definitive host species in Korea. Further studies on Anisakis infection in other cetacean species and marine mammals in Korean seas are warrantedi>Anisakis.

Eight cases of canine thelaziosis found in two localities in Korea.

Thelazia callipaeda, a parasitic nematode that causes thelaziosis in various mammals, including humans, is known to be endemic in Korea. However, life cycle-related information on the parasite, primarily from human infection and a few dog cases, is limited. This study reports additional cases of T. callipaeda infections in dogs from both rural and urban areas in Korea, indicating the potential for transmission to humans and other animals. We collected 61 worms from 8 infected dogs from Paju and Cheongju Cities and observed their morphological characteristics under a light microscope. The findings indicate that T. callipaeda infections in animals in Korea may be underestimated and are distributed close to human environments. Our results contribute to the growing knowledge of the reservoir hosts of T. callipaeda in Korea and highlight the importance of continued surveillance and research to prevent and control this emerging zoonotic disease.

Immediate Effects of Ankle Mobilization on Range of Motion, Balance, and Muscle Activity in Elderly Individuals with Chronic Ankle Instability: A Pre-Post Intervention Study.

BACKGROUND This study aimed to identify the immediate effect of applying ankle mobilization to the elderly with chronic ankle instability on the range of joint motion, balance, and lower extremity muscle activity. MATERIAL AND METHODS This study, the Cumberland Ankle Instability Tool (CAIT) was used to evaluate chronic ankle instability, and as a result, 65-year-olds with a score of 24 or less were conducted. In this study, the grade III of Maitland mobilization was used to increase the range of joint motion in older people with chronic ankle instability. And four joint mobilizations were administered for a total of 40 minutes, 10 minutes per run. In the pre-examination, the range of motion of ankle joints, balance, and lower extremity muscle activity in the Limit of Stability (LOS) position prior to ankle mobilization. The reexamination was taken a right after the intervention to see the immediate effect of applying joint mobilization. This study was conducted after receiving the approval of the Institutional Review Board of the Korea National University of Transportation. RESULTS The study results show that, as a result of applying the ankle mobilization intervention, the range of dorsi flexor and plantar flexor motion increased, resulting in the improvement of balance and an immediate effect on the lower extremity muscle activity when measuring the Limit of Stability. CONCLUSIONS The conclusion of this study is ankle mobilization may be a useful intervention method in preventing falls and improving balance in older adults with chronic ankle instability.

Microplastics in large marine animals stranded in the Republic of Korea.

Microplastics (MPs) are found in every ocean and are frequently ingested by marine animals. This study analyzed MPs in the stomachs and intestines of 12 large marine animals comprising one fin whale (Balaenoptera physalus), seven finless porpoises (Neophocaena asiaeorientalis), two loggerhead turtles (Caretta caretta), one Indo-Pacific bottlenose dolphin (Tursiops aduncus), and one common dolphin (Delphinus delphis) that were stranded off the Republic of Korea between 2019 and 2021. MPs were detected with a mean abundance of 3.42 ± 3.2 items/g and were predominantly of transparent-white, fragment-shaped polypropylene smaller than 200 µm. The abundance of MPs found did not correlate with the biological information (maturity, body length) of the finless porpoises and there were no significant differences in the abundance of MPs between the stomachs and intestines. These results cannot accurately assess the impact of MPs on large marine animals, so further studies are necessary to understand how MPs can potentially affect them.

Lipid Emulsion Treatment for Drug Toxicity Caused by Nonlocal Anesthetic Drugs in Pediatric Patients: A Narrative Review.

OBJECTIVE: Lipid emulsion (LE) has been used to treat children with cardiovascular collapse induced by toxic doses of nonlocal anesthetics with high lipid solubility. We aimed to analyze case reports on LE administration for resuscitation of toxicity induced by these drugs in pediatric patients. METHODS: Case reports involving pediatric patients undergoing LE treatment for toxicity caused by nonlocal anesthetic drugs until December 31, 2021, were searched through PubMed and Scopus using the following terms: "toxicity, or intoxication, or poisoning, or overdose" and "LE or intralipid." RESULTS: Twenty-eight cases on LE treatment for toxicity induced by nonlocal anesthetic drugs in pediatric patients (younger than 19 years) were retrieved. The total number of patients was 31. Lipid emulsion treatment was carried out during toxicity caused by amitriptyline, flecainide, bupropion, propranolol, and lamotrigine, which was unresponsive to supportive treatment. These drugs are highly lipid-soluble and inhibit cardiac sodium channels, which is similar to pharmacological properties of the local anesthetic bupivacaine. The most frequent method of delivery involved bolus administration followed by continuous infusion; 1.5 mL/kg LE administration followed by 0.25 mL/kg/min LE was most frequently used. Lipid emulsion improved various symptoms of drug toxicity in 29 patients (29/31, 93.54%), and symptoms were improved in 14 patients (14/31, 45.16%) within an h after LE administration. The trend in frequency of improved symptoms after LE treatment was as follows: the cardiovascular symptom alone > symptoms of the central nervous system alone > symptoms of the cardiovascular and central nervous systems. The adverse effects of LE treatment in the reported cases were hypertriglyceridemia, mild pancreatitis, and elevated levels of aspartate and alanine aminotransaminases. CONCLUSIONS: Lipid emulsion treatment may be effective in ameliorating intractable cardiovascular depression when systemic toxicity caused by drugs, including cardiac sodium channel blockers, is unresponsive to supportive treatments.