The relationship between oral and gut microbiota in alcohol dependence (AD) is not well understood, particularly the effects of oral microbiota on the intestinal microbiota. The current study aimed to explore the association between oral and gut microbiota in AD to clarify whether oral microbiota could ectopically colonize into the gut.16S rRNA sequence libraries were used to compare oral and gut microbial profiles in persons with AD and healthy controls (HC). Source Tracker and NetShift were used to identify bacteria responsible for ectopic colonization and indicate the driver function of ectopic colonization bacteria.p < 0.05). Principal coordinate analysis indicated greater similarity between oral and gut microbiota in persons with AD than that in HC, and oral-gut overlaps in microbiota were found for 9 genera in persons with AD relative to only 3 genera in HC. The contribution ratio of oral microbiota to intestinal microbiota composition in AD is 5.26% based on Source Tracker，and the AD with ectopic colonization showed the daily maximum standard drinks, red blood cell counts, hemoglobin content, and PACS scores decreasing .The α-diversity of oral microbiota and intestinal microbiota was significantly decreased in persons with AD (all Results highlight the connection between oral-gut microbiota in AD and suggest novel potential mechanistic possibilities. Neisseria, are known to participate in the metabolism of nitrate and acetaldehyde, perhaps contributing to AD-related cognitive impairment  and elicit neuroinflammation (Alcohol dependence (AD) causes physical and psychological damage to patients and contributed to more than 3 million deaths in 2016, accounting for 5.3 percent of total global mortality . Alcoholpairment . And incammation .Both oral and gut microflora may thus contribute to the pathogenesis of AD, but little is known about the association between the two bacterial populations. Healthy people generate and swallow about 1.5 L of saliva per day containing an enormous number of oral microbiota and metabolites . Normal The current study investigated whether oral microbiota could be ectopically colonized into the gut and whether those ectopic colonization bacteria are related to clinical features in AD. Findings from this study may contribute to a better understanding of oral-gut microbiota in AD, expose potential mechanisms and inform therapeutic strategies of AD in clinical practice.Thirty-three male patients diagnosed with alcohol dependence were recruited from the Second People’s Hospital of Guizhou Province during July and September 2019. alcohol dependence was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV). Other than nicotine dependence, as determined by the Mini International Neuropsychiatric Interview (M.I.N.I), patients did not present with other substance use disorders or other DSM-VI mental health or Axis I disorders. Twenty-one male healthy controls (HC) without somatic and psychiatric illnesses were also recruited. HC did not have a current or lifetime history of alcohol use or other substance use disorders. The inclusion and exclusion criteria are shown below.The inclusion and exclusion criteria are shown below. The inclusion criteria for the alcohol dependence (AD) group were as follows: (1) diagnosis of AD according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV); (2) Han Chinese males aged 18–60 years. The exclusion criteria for the AD group were as follows: (1) had or having the infectious disease; (2) had or having heart, brain, liver, kidney, oral and other serious diseases; (3) had or having metabolic diseases that can lead to the abnormal immune system; (4) had or having neurodegenerative diseases; (5) used antibiotics, steroids or other microbiota-modulating medications within 2 months before enrollment; (6) previous or current DSM-IV diagnosis of schizophrenia, depression, anxiety disorder, bipolar disorder, mental retardation, dementia (excluding mild cognitive function), and substance dependence other than alcohol and nicotine; (7) had irregular eating habits that affected oral flora  in recent 2 months; (8) alcohol abstinence longer than 1 week. The inclusion criteria for the HC group were as follows: Han Chinese males aged 18–60 years. The exclusion criteria for the HC group were as follows: (1)–(8) exclusion criteria for patients with alcohol dependence but (6) patients with a previous or current DSM-IV diagnosis of schizophrenia, depression, anxiety disorder, bipolar disorder, mental retardation, dementia (excluding MCI), and substance dependence, including alcohol (excluding nicotine); (9) drinking alcohol during sample collection.G*Power3.1.9.7 software was used to calculate the sample size, and it was assumed that the test standard α = 0.05 , the effect value was 0.5, the beta value was 0.20, and the degree of certainty (1-β) was 0.80. It was calculated that the minimum sample size required was 18.All subjects gave written informed consent for the collection of saliva and feces and participation in the study.All experiments were conducted by the Helsinki Declaration of 1975 and the ethical standards of the home institution Committee on Human Experimentation. Ethical approval was granted by the ethics committees of Peking University Sixth Hospital  and the Second People’s Hospital of Guizhou Province.Clinical features of AD participants were indexed, including withdrawal days, dependence years, first drinking age (FD age), frequency of drinking weekly (FREW), frequency of drinking daily (FRED), average standard drinks per day (ASD), maximum standard drinks per day (MSD), smoking status, body mass index (BMI), aspartate aminotransferase (AST), alanine transaminase (ALT), gamma-glutamyl transpeptidase (GGT), total bilirubine (TBIL), red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), triiodothyronine (TT3), tetraiodothyronine (TT4), thyroid stimulating hormone (TSH); alcohol withdrawal syndrome , alcohol craving , cognitive function , nicotine consumption , sleeping patterns  and symptoms of anxiety /depression  were recorded. Control subjects were assessed for cognitive function, depression and anxiety, and sleeping patterns.All subjects fasted overnight and did not brush their teeth. Fresh saliva and feces were collected at 7:00 to 8:00 am into sterile EP tubes. Saliva was collected after patients had rinsed the mouth with water 5 min beforehand and 1–2 ml of naturally secreted saliva was removed by Pap dropper into an EP tube. The procedure was repeated once. Feces were collected after patients had urinated to avoid contamination and defecated into a clean bedpan, from which 1–2 g stool, which had not been exposed to air, was removed with a sampling spoon. The procedure was repeated once. All samples were frozen in liquid nitrogen for 1 min and stored at −80°C. All samples were collected by procedures specified in the Human Microbiome Project (HMP) version 12 standard process .g for 10 min. The supernatant was transferred to a deep well plate with magnetic beads binding solution and DNA was transferred to a 1.5 ml centrifuge tube. DNA concentration and purity were assessed by NanoDrop 2000 micro-ultraviolet spectrophotometer and quantified with a Qubit Fluorometer using Qubit® dsDNA BR Assay kit . DNA quality was checked by running an aliquot on 1% agarose gel.DNA was extracted from the oral and gut microbial community using NEBnext microbiome DNA enrichment kit . The detailed procedure following the manufacturer’s instructions, including 600 μl Buffer with magnetic beads +20 μl Proteinase K + 5 μl RNase A was added to 96-well deep plates before washing three times and adding 100 μl Elution Buffer. 100–200 mg sample was transferred to the centrifuge tube with grinding beads and 1 ml Buffer (ATL/PVP-10) added and the sample was ground and incubated at 65°C for 20 min before centrifugation at 14000 × g for 5 min. 0.6 ml Buffer PCI was added with mixing by vortex for 15 s and centrifugation at 12000 × Variable regions, V3 ~ V4, of the bacterial 16S rRNA gene, were amplified with degenerate PCR primers, 515F (5′-GTGCCAGCMGCCGCGGTAA-3′) and 806R (5′-GGAC TACHVGGGTWT-CTAAT-3′) and products purified by Agencourt AMPure XP beads and eluted with elution buffer. Agilent Technologies 2,100 bioanalyzer qualified the Libraries and sequenced using an Illumina HiSeq 2,500 platform , following the manufacturer’s instructions. 2 × 250 bp paired-end reads were generated. Raw reads were filtered and paired-end reads were tagged for clustering into operational taxonomic units (OTUs). OTU representative sequences were taxonomically classified using Ribosomal Database Project (RDP) Classifier v.2.2 with a minimum confidence threshold of 0.6 and trained on the Green-genes database v201305 by QIIME 2 . Alpha aDifferent classification levels were plotted with R package v3.4.1 and R package “gg plots” . PrincipDNA extraction, 16S rRNA sequencing, and analyses were performed by BGI Co., LTD. Shenzhen, China.https://github.com/danknights/sourcetracker. NetShift was used to quantify oral and gut community changes between the AD and HC to identify the microbial taxa which serve as “driver-bacteria,” promoting the change from the healthy to the diseased state. The correlation network was established based on the Pearson coefficients between bacteria communities in AD and HC. Each genus was regarded as a point in the network and the genus with a significant correlation relationship was assigned an edge . Discontinuous variables were analyzed by the chi-square test. The α-diversity index and β-diversity index were calculated and compared between HC and AD microbiota. Principal coordinate analysis (PCoA) was used to evaluate the species differences in the microbiota between different sample groups. Based on the Wilcoxon test, calculated the characteristics of composition in oral/gut microbiota between AD and HC from phylum to genus. Oral-gut overlap microbiota based on common OTUs number by VeenDiagram package in R. Comparison of clinical features between ectopic colonization (EC) patients and no ectopic colonization (NE) patients by Mann–Whitney U test. Correlational analyses were assessed by the Spearman test. The value of p < 0.05 was considered statistically significant.Statistical analyses were performed with IBM SPSS 23.0, R-4.2.0, and Graphpad prism 8.0.2. Differences in numerical variables between AD and HC, continuous variables consistent with normal distribution and homogeneity of variance were assessed by a two-tailed Student’s p < 0.001), and MoCA scores were lower for AD than for HC (p < 0.05). Demographic and clinical characteristics of the study population are summarized in No significant differences were present in age, occupation, educational status, marital status, annual income, BMI, or smoking status. No significant difference in FTND was found, but HAMD, HAMA, and PSQI scores were higher for AD than for HC  and intestinal microbiota  was significantly decreased in AD, compared with HC in p < 0.05). Based on weighted Unifrac, the β-diversity of oral microbiota between AD and HC exhibited statistical difference (p < 0.01); and based on weighted Unifrac, the β-diversity of gut microbiota between AD and HC exhibited statistical difference (p < 0.001) in p < 0.05), in The β-diversity between oral and gut microbiota in AD  and HC  exhibited significant difference in β-diversity heatmap and principal coordinate analysis (PCoA) both indicate that the difference between oral and gut microbiota in AD was decreased compared to HC in p < 0.05), but four species had no significant differences between oral and gut microbiota in the top 10 species of AD in Based on unweighted Unifrac and weighted Unifrac to explore the relationship between oral and gut microbiota found that Prevotella, Streptococcus, Veillonella, Neisseria, Fusobacterium, Haemophilus, Alloprevotella, Megasphaera, and Bacteroides. And the genus of Fusobacterium, Alloprevotella, and Veillonella also are the oral/gut microbiota overlap for HC. Therefore, there were 6 AD oral/gut overlap genera, Prevotella, Streptococcus, Neisseria, Haemophilus, Megasphaera, and Bacteroides, that were not found in the HC oral/gut overlap microbiota ; Neisseria is positively correlated with AST, MCV, and TSH , and negatively correlated with RBC ; Haemophilus is positively correlated with education years, scores of MoCA , and negatively correlated with age, alcohol dependence years ; Bacteroides is positively correlated with age, smoking years , and negatively correlated with daily alcohol consumption . And in the relative abundance of gut microbiota, found that Prevotella is positively correlated with frequency of drinking (daily) ; Streptococcus is negatively correlated with HB  and positively correlated with TT3 ; Haemophilus is positively correlated with education years ; Megasphaera is negatively correlated with daily alcohol consumption, BMI, GGT, scores of PACS, scores of HAMD   .Abiotrophia, Actinomyces, Alloprevotella, Bacteroidales, Blautia, and Campylobacter…, are shown in p < 0.05) in Prevotella, Neisseria, and Saccharibacteria in the level of the genus were found by Netshift analysis, and they were also belonging to ectopic colonization bacteria in Source Tracker analysis explored the ectopic colonization of oral microbiota in the gut, showing five AD, No. 3, 7, 9, 16, and 21, had a fraction of their gut microbiota which had originated from the oral cavity, but no positive results in HC. The specific oral bacteria involved in ectopic colonization, Alloprevotella is positively correlated with first drinking age and ALT , Escherichia is negatively correlated with AST , Fusobacterium is positively correlated with MCV . Lachnospiracea_incertae_sedis is negatively correlated with frequency of drinking (weekly), AST, ALT, GGT, and TSH . Megasphaera is negatively correlated with average standard drinks per day, scores of PACS, scores of HAMD, and BMI . Prevotella is positively correlated with frequency of drinking (daily) . Saccharibacteria is negatively correlated with TBiL . Streptococcus is negatively correlated with HB  in Based on the Spearman correlation test, to explore the association between ectopic colonization bacteria in the relative abundance of gut microbiota and clinical features in AD. The exploration of the relationship between oral and gut microbiota revealed that differences between oral and gut microbiota decreased and the oral/gut microbiota overlap increased in AD, compared with HC. Genera involved in ectopic colonization of oral microbiota to gut were shown connected with AD symptom severity based on Source Tracker and NetShift analysis. Compared with previous studies which only focused on single niche, the current study emphasized the oral-gut microbiota axis and the connection between oral and gut microbiota in AD . To the α-diversity of oral and intestinal microbiota decreased in AD, this change may predispose patients to inflammatory responses and metabolic disorders   . And theHowever, the question of what causes changes in the association between oral and gut microbiota and whether oral microbiota can ectopically colonize the gut in AD needs to be answered by the approaches of Source Tracker and NetShift. The contribution ratio of oral microbiota to the composition of intestinal microbiota in AD is 5.26%, and no ectopic colonization was found in HC. Among the current study, those showing ectopic colonization often suffered lower red blood cell counts and hemoglobin content, meanwhile, their daily maximum standard drinks and craving for alcohol were also lower than non-ectopic colonization. This reduction in craving seems to confirm the prevailing hypothesis of the work that ectopic bacteria from the oral cavity to the gut contribute to the pathological state, because low red blood cell counts and hemoglobin content represent the poor state of nutrition in AD, and impaired nutritional status often with lower levels of ghrelin and alcohol craving, and consumed high quantity of ultra-processed food had higher obsessive thoughts about alcohol . Thus, ePrevotella, Neisseria, and Saccharibacteria, were also belonging to ectopic colonization of oral bacteria based on NetShift analysis. Previous studies found that, Prevotella is an opportunistic pathogen that may increase branched-chain amino acid (BCAA) synthesis in the gut and lead to insulin resistance   and increase the estimated glomerular filtration rate (eGFR)   . Bacterose model . Sacchar= 0.003) , and was= 0.003) .Fusobacterium nucleatum, Porphyromonas gingivalis, and Klebsiella spp., aggravate gut dysbiosis and favor pro-inflammatory bacteria , average standard drinks per day, BMI, AST, ALT, GGT, TBIL, HB, MCV, TSH, PACS scores and HAMD scores. Therefore, the presence of the ectopic genera may be an objective indicator of disease severity. Meanwhile, the current study also compared the species’ relative abundance of 6 oral/gut overlap bacteria with clinical characteristics, further combining the results in bacteria , and actbacteria . Further the gut . Meanwhi the gut . Thrombo the gut . Low-gra the gut . Inflamm the gut   can be found at: The studies involving human participants were reviewed and approved by the Helsinki Declaration of 1975 and the ethical standards of the home institution Committee on Human Experimentation. Ethical approval was granted by the ethics committees of Peking University Sixth Hospital  and the Second People’s Hospital of Guizhou Province. The patients/participants provided their written informed consent to participate in this study.LH, ZN, LL, and HS were responsible for the study concept and design. KZ contributed to the acquisition of human data. LH, YK, and ZY performed the gut and oral microbiota analysis. YK and XG assisted with data analysis and interpretation of findings. XL provided critical revision of the manuscript for important intellectual content. All authors critically reviewed the content and approved the final version for publication.Our study got support from the National Natural Science Foundation of China  and the National Clinical Research Center for Mental Disorders  NCRC2020M09.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Colon cancer is a particularly prevalent malignancy that produces postoperative complications (POCs). However, limited imaging modality exists on the accurate diagnosis of POCs. The purpose of this study was therefore to construct a model combining tumor spectral CT parameters and clinical features to predict POCs before surgery in colon cancer.This retrospective study included 85 patients who had preoperative abdominal spectral CT scans and underwent radical colon cancer resection at our institution. The patients were divided into two groups based on the absence (no complication/grade I) or presence (grades II–V) of POCs according to the Clavien-Dindo grading system. The visceral fat areas (VFA) of patients were semi-automatically outlined and calculated on L3-level CT images using ImageJ software. Clinical features and tumor spectral CT parameters were statistically compared between the two groups. A combined model of spectral CT parameters and clinical features was established by stepwise regression to predict POCs in colon cancer. The diagnostic performance of the model was evaluated using the receiver operating characteristic (ROC) curve, including area under the curve (AUC), sensitivity, and specificity.40keV-VP and VFA were independent predictors of POCs. The combined model based on predictors yielded an AUC of 0.84 (95% CI: 0.74–0.91), with a sensitivity of 77.8% and specificity of 87.9%.Twenty-seven patients with POCs and 58 patients without POCs were included in this study. MonoE40keV-VP and VFA can predict POCs before surgery in colon cancer and provide a basis for individualized management plans.The model combining MonoEThe model combining MonoE40keV-VP and visceral fat area can predict postoperative complications before surgery in colon cancer and provide a basis for individualized management plans.• Visceral fat area and MonoE40keV-VP were independent predictors of postoperative complications in colon cancer.• The combined model yielded a high AUC, sensitivity, and specificity in predicting postoperative complications.• The combined model was superior to the single visceral fat area or MonoE40keV-VP in predicting postoperative complications. Colon cancer is the third most common cancer in the world and the second leading cause of cancer-related death . AlthougTo the best of our knowledge, all studies performed so far found that visceral obesity is an independent predictor of POCs in colon cancer, and obese patients are more likely to have complications, such as anastomotic fistula and wound infection –7. CurreColon cancer has different histopathological subtypes, with heterogeneities within and between tumors. Intra-tumor heterogeneity may contribute to different subtypes and various gene expressions within the tumor, which may affect the treatment outcome . ContrasCT technology has advanced rapidly, and the emerging spectral CT imaging technology can provide more quantitative information about the inside of tumors. Combining quantitative and qualitative information, spectral CT can provide virtual monoenergetic images (MonoE) to enhance image contrast, an iodine density map can quantify the iodine content inside the tumor that reflects the density of blood vessels, effective atomic number map can reflect on material information, which is mostly applied to stone composition, and the energy spectrum curve can reflect on the degree of attenuation of the material –18. SpecTherefore, this study aimed to establish a predictive model combining clinical features and tumor spectral CT parameters for the effective prediction of POCs in colon cancer to develop individualized treatment plans.1-2N0M0), stage II (T3-4N0M0), stage III (TanyN1-2M0), and stage IV (TanyNanyM1). Epidermal growth factor receptor (EGFR) expression levels of tumor were determined by immunohistochemical examination from the department of pathology. Clinical baseline characteristics of these two groups of patients were recorded from digital clinical files of PACS.This retrospective study initially included 187 consecutive patients with pathologically confirmed colon cancer postoperatively from picture archiving and communication systems (PACS) in our hospital from August 2021 to March 2023. The inclusion criteria were as follows: (1) patients over 18 years of age who underwent radical colon cancer surgery, including the removal of the colonic segment harboring the tumor with proximal and distal 10 cm margins, complete mesocolic excision (CME) with central vascular ligation and D3 lymphadenectomy; (2) abdominal spectral CT imaging scans were performed within two weeks before surgery; (3) the surgical procedures were performed by senior clinicians and nurses with more than 10 years of experience in treating colon cancer in the department of surgical gastroenterology. The exclusion criteria were as follows: (1) CT images with poor quality and large lesion artifacts; (2) patients who had preoperative radiotherapy or neoadjuvant chemotherapy; (3) patients with a short diameter of the colon tumor of < 5 mm, which might have prevented the placement of ROI and impacted the measurement of intra-tumor spectral CT parameters; (4) patients with other malignant tumors in the body, which might have affected the patient’s physical condition; (5) patients with incomplete clinicopathological data; (6) postoperative follow-up time of < 30 days and without POCs. Finally, eighty-five patients with colon cancer were selected for further analysis, as shown in the patient selection flow chart  with an unenhanced and dual-phase enhanced scan. The main parameters were tube voltage of 120 kVp, automatic tube current modulation, collimation of 64 × 0.625 mm, pitch value of 0.99, X-ray tube rotation speed of 0.75 s, and the reconstruction slice thickness of 1.0 mm. A contrast enhancement scan was performed with a fully automatic high-pressure syringe by injecting 80 mL of iodixanol (320 mgI/mL) through the elbow vein at a rate of 3.0 mL/s. The scan was triggered at the level of the coeliac trunk of the abdominal aorta in the arterial phase with a threshold of 150 HU. The scan was delayed by 70 s in the venous phase. Both conventional images and spectral-based images (SBI) data were reconstructed.Visceral fat area (VFA) and subcutaneous fat area (SFA) were measured semi-automatically on L3 horizontal cross-sectional unenhanced CT images (plain scans were obtained before contrast-enhanced images) by a radiologist with 10 years of experience in the diagnosis of abdominal spectral CT imaging who was unknown about the patient’s outcome, using ImageJ software, as shown in the schematic diagram Fig. . The CT 40keV-AP, MonoE40keV-VP, IoDAP, IoDVP, Z-effAP, and Z-effVP. The arterial enhancement fraction (AEF) values of colon cancer were further calculated using the formula of AEF = IoDAP/IoDVP. The slope of the energy spectrum curve (λ) was calculated as (CT40 kev-CT70 kev)/(70–40). The average of all colorectal tumor spectral CT parameters measured by two physicians was taken as the final recorded value.The spectral CT images, including virtual monoenergetic images (MonoE), iodine density (IoD), Z effective atomic number (Z-eff), and the energy spectrum curve, were generated from spectral base images (SBI) data package via post-processing workstation . Two radiologists with 8 and 10 years of experience in diagnostic imaging, respectively, opened thin-layer (1 mm layer thickness) spectral CT images on a Philips post-processing workstation ISP (Image and information management software version 10.1.5) in the arterial phase (AP) and venous phase (VP) and drew a circular ROI on the largest cross-sectional AP image of the colon tumor, avoiding areas of necrosis visible to the naked eye, and the ROI was copied onto the VP image with manual fine-tuning. Both physicians were unaware of the patient's postoperative results and recorded the values of the respective parameters of the colon tumor, such as conventional CT value (C) of the AP and VP, MonoEhttp://www.R-projetc.org). Interobserver agreements on the tumor spectral CT parameters were tested by the intraclass correlation coefficient (ICC), and with ICC > 0.75 indicating a good consistency. Quantitative data conforming to a normal distribution was expressed as mean ± standard deviation, an independent samples t-test was used to compare cancer with POCs and cancer without POCs, and those not normally distributed were expressed as median , and the Mann–Whitney U test was used for the comparison between the two groups. Qualitative information was expressed as frequency (percentage), and the comparison between the two groups was done using the appropriate chi-square test or Fisher’s exact test. The clinical features and spectral CT parameters that were statistically different were analyzed by stepwise regression to obtain independent predictors to POCs and build a predictive joint model. The diagnostic performance of the prediction model, including area under the curve (AUC), sensitivity, and specificity, was assessed using the receiver operating characteristic (ROC) curve. A p value of < 0.05 was considered statistically significant between the two groups.Statistical analyses were performed using SPSS 26.0 software , MedCalc software version 15.11.4 , and R software , such as lung infection (n = 3), abdominal infection (n = 10), and incisional infection (n = 4); anastomotic fistula (n = 2), pancreatic leakage (n = 3), multiple organ failure (n = 2), and blood transfusion and total parenteral nutrition (n = 3). When comparing the clinical baseline characteristics of the two groups, statistical differences were found in gender, EGFR expression, VFA, and VFA/SFA ; the rest of the clinical characteristics were not statistically different between the two groups . The detailed results are shown in Table In the recruited 85 colon cancer patients, there were 60 men and 25 women, with an age range of 30–85 years and a median age of 65 years. Twenty-seven patients 31.8%) were with POCs and 58 patients (68.2%) were without POCs on the basis of clinician’s diagnosis of postoperative medical history records from PACS database and the Clavien-Dindo grading system. POCs included infections    Fig. . Other t5) Table . Two repp = 0.002], and tumor spectral CT parameter MonoE40keV-VP  were independent predictors of POCs in colon cancer, and a predictive joint model established from these two predictors yielded an AUC of 0.84 (95% CI: 0.74–0.91), with a sensitivity of 77.8%, and specificity of 87.9%. Similarly, VFA from clinical characteristics produced an AUC of 0.76 (95% CI: 0.66–0.85) with a sensitivity of 81.5% and specificity of 81%. The spectral CT parameters of MonoE40keV-VP produced an AUC of 0.75 (95% CI: 0.64–0.84), with a sensitivity of 66.7% and specificity of 77.6% : 1.021 (95%CI: 1.007–1.035); 40keV-VP based on an AUC of 0.75. Further, the clinical characteristic VFA was associated with POCs in colon cancer. Subsequently, a novel combined prediction model was constructed by incorporating two independent predictor variables, such as MonoE40keV-VP and VFA through stepwise regression and yielded an AUC of 0.84 with a sensitivity of 77.8% and specificity of 87.9%, showing good predictive performance.POCs in colon cancer were associated with the spectral CT parameter MonoESpecific to clinical characteristics, the VFA was an independent predictor of POCs in colon cancer. Patients with large VFA were more likely to have POCs, the greater the VFA/SFA value, the greater the distribution of visceral fat and the greater the risk of POCs for patients, which was consistent with previous studies –7. HowevIn recent years, predictive models for POCs in colon cancer were developed but the models were mainly based on the clinicopathological characteristics, including the VFA of the patients , 31. Kur40keV-AP, λAP, MonoE40keV-VP, IDVP, Z-effVP, and λVP. The higher the value of the spectral CT parameter of the tumor indicated the richer the blood supply in the tumor and the more pronounced enhancement. The richer blood supply was associated with faster tumor growth, and the more aggressive tumors were more likely to invade the surrounding tissues, thus affecting the patient’s survival and prognosis [p < 0.05) in VP than AP between patients with POCs and without POCs, which may be related to the delayed enhancement of colon cancer, and the features of the VP were more clearly related to the intensification of microvessels and better reflected the characteristics of the tumor, which was consistent with a previous study [40keV-VP was the independent predictor and predicted POCs in colon cancer, yielding an AUC of 0.75, but the results were still not good.Regarding tumor spectral CT parameters, spectral CT imaging reflected the blood supply to the tumor by quantifying the iodine content of the local tissue, thereby revealing intra-tumor heterogeneity and predicting patient prognosis . In addirognosis . Furtherus study . Spectra40keV-VP as independent predictors of POCs in colon cancer by stepwise regression analysis, and a combined prediction model was established, which showed a better predictive effect (AUC = 0.84) with a sensitivity of 77.8% and specificity of 87.9%. Cao et al. [Further, we found the patient’s clinical characteristic VFA, and tumor spectral CT parameter MonoEo et al.  combinedThis study still had some limitations. First, the small sample size of patients undergoing radical colon cancer in this study may have resulted in some selection bias. A larger cohort is requested. Second, this study only outlined the circular region of interest at the largest tumor level, which may have resulted in the loss of some biological information. A whole tumor mean calculation was yet to be performed to analyze whether there was a statistical difference from a single level. Third, this study was a single-center retrospective study and the prediction model we developed lacked external validation. A further multicenter prospective study is pending, aiming to optimize the generalizability and performance of the prediction model. Fourth, in this study, POCs were diagnosed on the basis of clinician’s diagnosis from medical records alone. Diagnoses such as multiple organ failure, blood transfusion and total parenteral nutrition may well be taken from medical records. However, the situation is different when it comes to infections where most cases are diagnosed not only on the basis of clinical signs, lab values, etc., but also based on imaging. This especially applies to complications such as abdominal infection, anastomotic fistula, and pancreatic leakage which were recorded in the medical records of some patients. So the lack of CT confirmation and/or re-evaluation of images in our retrospective study may have resulted in some bias.40keV-VP, which well-predicted POCs in colon cancer underwent surgery and provided a basis for personalized treatment for colon cancer patients.In conclusion, we constructed a combined model based on the patient’s VFA and the tumor spectral CT parameter MonoE


Our goal was to conduct a scoping review of the literature on the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy in children, focusing on treatment targets and treatment initiation timing. We performed literature searches using PubMed for articles reporting treatments of infection-triggered encephalopathy syndrome/acute encephalopathy. We included articles describing specific treatments for acute encephalopathy with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series studies without control groups in this review, if the studies contained at least two cases with clear treatment goals. Therapies were classified based on their mechanisms of action into brain protection therapy, immunotherapy, and other therapies. We operationally categorized the timing of treatment initiation as T1 (6–12 h), T2 (12–24 h), T3 (24–48 h), and T4 (>48 h) after the onset of seizures and/or impaired consciousness. Thirty articles were included in this review; no randomized control study was found. Eleven retrospective/historical cohort studies and five case–control studies included control groups with or without specific therapies or outcomes. The targeted conditions and treatment timing varied widely across studies. However, the following three points were suggested to be effective in multiple studies: (1) Careful seizure management and targeted temperature management within 12 h (T1) of onset of febrile seizure/prolonged impaired consciousness without multiple organ failure may reduce the development of acute encephalopathy with biphasic seizures and late reduced diffusion; (2) immunotherapy using corticosteroids, tocilizumab, or plasma exchange within 24 h (T1–T2) of onset of acute necrotizing encephalopathy may reduce sequelae; and (3) anakinra therapy and ketogenic diet demonstrate little evidence of neurologic sequelae reduction, but may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks (T4) after onset in children with febrile infection-related epilepsy syndrome. Although available studies have no solid evidence in the treatment of infection-triggered encephalopathy syndrome/acute encephalopathy, this scoping review lays the groundwork for future prospective clinical trials. In a national survey in Japan, 34.6% of patients with AE developed mild to severe neurological sequelae . AE is a2.This scoping review was conducted using the PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation .2.1.The following question was set for this scoping systematic review: What are the effective specific therapies for children with ITES/AE? AE was defined based on the Japanese Society of Child Neurology guidelines for the diagnosis and treatment of AE in childhood . The con2.2.We performed literature searches with PubMed for English articles on the treatment of ITES/AE in humans. Searches were performed independently by two authors, HN and MN, using agreed search terms, and the results were combined. To obtain specific AE treatment or management modalities, we searched the following keywords on May 23, 2023: “ AND ) AND  AND (humans[Filter]) AND ). Searches were also performed manually.2.3.We included articles describing specific treatment modalities for AE with control groups. For the purpose of searching new therapies only experimentally tried in the case series, we also included case series separately from studies with control groups in the review, if they contained two or more cases with clear treatment goals. Eligible articles were identified by performing an initial screen of titles and abstracts, followed by a full review of selected articles. All retrospective and prospective studies that met these criteria were selected.2.4.The following data were extracted from the selected articles: patient demographics, type of study , therapies , outcomes, adverse events, and other therapies. When considering specific treatments for AE; moreover, therapies were classified, based on mechanisms of action, into immunotherapy, brain protection therapy, and other therapies. In addition, it is important to clarify the timing and target of each treatment. In this study, we operationally categorized the timing of treatment initiation as T1–T4 : T1 incl3.3.1.3.2.Thirty articles were included in the review, none of which was a randomized control study. Eleven retrospective/historical cohort studies and five case–control studies included control groups with or without specific therapies or outcomes , 3. Four4.Since the 1970s, many AE treatment options have been reported in patients with Reye syndrome; however, this scoping review revealed limited evidence for AE treatment efficacy. This review found no randomized control trial evaluating the AE treatment efficacy; only 16 retrospective cohort and case–control studies with control groups as well as 14 case series reports of at least two patients were found. In the present study, we classified the treatment options into brain protection therapy, immunotherapy, and other therapies, based on the mechanism of action of each treatment; moreover, we categorized the timing of treatment initiation after neurological symptom onset as follows: T1 (6–12 h), T2 (12–24 h), T3 (24–48 h), and T4 (>48 h). The timing of treatment initiation, target condition (confirmed diagnoses of AE or high risk of developing AE), and treatment goal  differed significantly among the studies. We have hereinafter discussed each treatment option based on the mechanism of action, timing of initiation, and target conditions.4.1.4.1.1.p = 0.004). Eight children with sequelae in the conventional care group fulfilled the diagnostic criteria for AESD, whereas no child without sequelae developed AESD. Murata et al. conducted a historical (retrospective) cohort study on children who underwent TTM at 36.0°C for 12–72 h combined with methylprednisolone (MP) use (TTM/MP) (p = 0.0433). No child (0%) and 4 (40%) children were finally diagnosed as having AESD in the TTM/MP and MP groups, respectively. TTM has a narrow time window; hence, the targeted temperature was reached within 12 h of the onset of impaired consciousness (T1) in many patients in the abovementioned two studies. n = 3/5], HSES [n = 4/1], AE with refractory seizures [n = 11/5], and others [n = 9/5] in patients with hypothermia/normothermia) did not improve outcomes. In a case–control study, Therapeutic hypothermia is theoretically effective for various brain injuries, and its mechanisms of action include reduction of oxygen and nutrient demand, suppression of glutamate and free radical production, suppression of apoptosis, suppression of inflammatory cytokine production, suppression of brain edema, and anticonvulsant effects . A recen(TTM/MP) . For chi4.1.2.p < 0.001). p = 0.014) as well as IVIG  and intravenous MP therapies  were significantly more applied in the non-death group; however, they did not describe the timing of barbiturate initiation.4.2.4.2.1.p = 0.044); nevertheless, the outcome of patients was not correlated with corticosteroid use, corticosteroid pulse therapy, or gammaglobulin use throughout the clinical course at T1–T4. E. coli O111 infection, who were classified according to neurological prognosis, Takanashi et al. reported that corticosteroid pulse therapy was associated with prognosis; however, this study was not included in the current analysis because 11 of the 21 participants were adults (p = 0.03) and the duration of ventilation . Therefore, although corticosteroid therapy is theoretically effective for AEs, the disease conditions, disease severity, and timing of treatment that result in clinical efficacy have not been sufficiently clarified. In our studies on the dynamics of inflammatory cytokines in patients with HSES (a cytokine storm-mediated AE) and ICU-treated patients with febrile status epilepticus, inflammatory cytokine levels peaked within 24 h after neurological symptom onset, followed by a gradual decline in cytokine levels ; nevertheless, multivariate analysis showed no significant association. Furthermore, the following three studies have compared outcomes with and without IVIG use in patients with AE: IVIG use for ANE was not associated with outcome (good prognosis in 2 of 5 patients exposed to IVIG use and in 5 of 12 patients without IVIG use) (T1–T4) (p = 0.43) or during the entire course (T1–T4)  did not effectively improve outcomes  ; IVIG us (T1–T4) ; and IVIoutcomes .In a case series study, 4.2.3.p = 0.011); however, the mortality rate at the final follow-up was not significantly different between the two groups . The improvement in liver enzymes was more rapid in the PE group. In a case report, two children with ANE were treated using intravenous MP combined with therapeutic PE (which started at 9 h and 16 h (T1–T2) from the onset) and TTM at normothermia, both of whom completely recovered  as well as ICU  and hospital length of stay . Among children with available seizure frequency data (n = 15), 11 exhibited >50% seizure occurrence reduction at 1 week of anakinra treatment. Although there were no statistically significant differences due to the small sample size, the median interval between seizure onset and anakinra initiation tended to be shorter in children with seizure occurrence reduction  than in those without seizure occurrence reduction  (T4). Nevertheless, there was no such tendency in terms of neurological outcomes at discharge (Recent studies have suggested that neuroinflammation may be involved in the pathogenesis of FIRES/AERRPS . Lai et ischarge . Shresthischarge . Sa et aischarge .4.2.5.p = 0.020) (Cyclosporine use can inhibit hypercytokinemia-associated apoptosis and prevent cytotoxicity and tissue damage progressions. = 0.020) . Matsuo = 0.020) . Three p4.2.6.In patients with ANE, brain injury is presumed to result from a cytokine storm; moreover, these patients reportedly have increased blood IL-6 levels in the acute phase . Only tw4.3.4.3.1.Energy depletion resulting from decreased mitochondrial function is a potential cause of AE. 4.3.2.The KD is an established and effective non-pharmacological treatment for drug-resistant epilepsy. Recently, there has been an increasing number of reports on the efficacy of KD for SRSE. Additionally, the KD has been attempted as a means of seizure control in children with FIRES, a severe form of AE characterized by prolonged RSE triggered by an unknown fever. Nabbout et al. conducted a study involving nine KD-treated patients with FIRES . The KD 4.3.3.A case series report has evaluated the efficacy of dextromethorphan (an NMDA receptor antagonist and sigma-1 receptor agonist for AESD) in four patients with mild consciousness disturbance  occurring 24 h after prolonged (>15 min) FS (near-miss AESD) and four patients with AESD. In patients with near-miss AESD, dextromethorphan was started on day 2 or 3 (T3–T4), and no patient developed secondary seizures and AESD. In patients with AESD, dextromethorphan and cyclosporine were started when the secondary seizure was observed on days 4–6 (T4); three of the four patients had normal cognition after 1–3 years of follow-up, whereas one patient showed mild neurological sequelae (hyperactivity) after 3 years. The authors suggested that dextromethorphan and cyclosporine could be effective for the treatment and prevention of AESD . Sa et a5.No randomized control trial has evaluated the AE treatment options; only 16 comparative studies with a control group and 14 case series reports with at least two cases are currently available. Disease conditions and the timing of treatment varied widely among the studies. Generally, the studies suggested that the treatments were effective in terms of ameliorating neurologic sequelae when administered within 12–24 h of AE onset. Moreover, treatments often targeted high-risk conditions prior to the diagnosis of AE syndromes. Nevertheless, KD and anakinra therapies may reduce seizure frequency and allow for weaning from barbiturates, even when administered weeks after onset in children with FIRES. This scoping review lays the groundwork for future prospective clinical trials.HN developed the main concepts and performed the scoping review and wrote the paper. MN performed the scoping review. All the authors reviewed and edited the manuscript and approved the final version.This study was supported by a Grant-in-Aid for Scientific Research (KAKENHI) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (Subject ID: 21K09047 to HN) and a Grant-in-Aid for Research on Measures for Intractable Diseases (21FC1005) from the Ministry of Health, Labor, and Welfare, Japan.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.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study investigates the impact of study-abroad experience (SAE) on lexical translation among 50 Chinese (L1)-English (L2) interpreting students. Participants were divided into two groups based on their experience abroad. Both groups consisted of 25 unbalanced L2 learners who were matched in age, working memory, length of interpreting training, and L2 proficiency. Bidirectional word translation recognition tasks, from L1 to L2 and L2 to L1, highlighted several key findings: (1) both groups were significantly more accurate and faster from L2 to L1 than in the reverse direction; (2) the study abroad (SA) group was more inclined to respond quickly at the risk of making errors, whereas the non-study abroad (NSA) group tended to be more cautious, prioritising accuracy over speed; (3) the SA group were more balanced and consistent in their performance across lexical translations in both directions than the NSA group. These results emphasise the potent effect of SAE in resolving bilinguals’ language competition, especially in streamlining language switching, a cognitive process critical for interpreting students engaging daily with dual languages. In any Though some interpreters are often recommended to interpret solely into their L1, many possess the capability for bidirectional interpreting—comprehending in one language and interpreting into another. Yet, it is commonly observed that they may not perform equally well in both directions . BilinguIncreasing attention has been paid to factors influencing bilingual lexical translation. Evidence points towards the impact of variables such as participants’ working memory , L2 profSAE, within the field of second language acquisition, is characterised as a type of L2 learning setting that differs from both purely natural exposure and classroom instruction. While natural exposure pertains to the spontaneous, untutored acquisition of a language in its native country, classroom instruction often refers to the teaching of a foreign language in a country where that language is not the primary mode of communication. For instance, one might learn English in Chinese classrooms, with the classroom being the primary, if not the sole, exposure to the language . SAE, hoPractically, this environment has been shown to increase L2 processing , suppresMost previous research on lexical development in the SAE context mainly concentrates on vocabulary knowledge growth, typically evaluated through word association and word recognition tasks. However, fewer studies have explored how SAE influences a bilingual’s command of two languages, particularly in terms of efficiency (speed and accuracy) and asymmetry in bidirectional lexical translation. Importantly, interpreting students, who consistently keep both languages active even in predominantly monolingual environments, are a unique subgroup of bilinguals . These sInvestigating the impact of SAE on interpreting students’ lexical translation performance could offer valuable insights into bilinguals’ lexical processing. Additionally, it may guide interpreting educators in developing effective training tasks to meet specific pedagogical objectives in both study-abroad and home-country classroom settings.2.2.1.Various models have been developed to elucidate the intricacies of bilingual lexical processing. For instance, the Hierarchical Model by Our current study predominantly draws upon the Inhibitory Control model introduced by The Inhibitory Control model postulates that the selection of the target language at any given time involves the suppression of the non-target one. This suppression process is overseen by the Supervisory Attentional System (SAS), a superior cognitive control mechanism that intervenes with the language system as needed. One of the key insights derived from the model is the relationship between language proficiency and inhibition. The more proficient a bilingual is in a language, the more effortlessly they can suppress the non-target language, and conversely, lesser proficiency might entail greater cognitive effort in this suppression . Inheren2.2.Lexical translation extends beyond a mere linguistic task; it is intrinsically woven with cognitive processes, especially those governed by working memory. As a fundamental pillar of cognitive resources, working memory is predictive of a host of intricate cognitive tasks, inclusive of language processing . At its Researchers suggest that the regular, habitual use of the bilingual control mechanism to reconcile the L1 and L2 competition should have cognitive benefits . Owing tA substantial body of evidence indicates that bilingual cognitive control capabilities can be moulded by diverse bilingual experiences and language use frequency e.g., . For ins2.3.Despite the prevalence of SAE in L2 learning programmes, research examining the effects of SAE on lexical processing remains limited and somewhat inconclusive . The majFor instance, within the realm of SAE and L2 lexical processing, Chinese speakers who spent an average of 6.5 years in the US demonstrated better performance in their speed and accuracy in recognising spoken L2 words. This suggests that SAE participants may possess a heightened capability to decipher talker variability and expedite nonnative language processing with fewer cognitive resources than their counterparts without such experience .The avenue of research addressing SAE’s influence on the decline of L1 availability has also yielded significant insights. Notably, studies have indicated that extended immersion in an L2 context amplifies the cognitive effort required for languages that are not regularly practised or used . A substOn another front, SAE also appears to shape bilinguals’ communication behaviours. A study by Collectively, these studies highlight the intricate interplay between the cognitive mechanisms honed through SAE and their subsequent manifestation in bilingual lexical processing.2.4.Fundamental questions remain regarding the impact of SAE on lexical translation. Notably, studies on Chinese-English language pairs, particularly with Chinese as L1 and English as L2, are significantly underrepresented—this is significant given the rising trend of Chinese students studying abroad in English-speaking countries . The uniIn light of these identified gaps, our study seeks to determine the effect of SAE on bidirectional word translation tasks among interpreting students with Chinese as L1 and English as L2. Specifically, we examine how SAE impacts their efficiency (measured by accuracy and response times) and direction-dependent asymmetry in bidirectional translation.Drawing from the literature that highlights the benefits of SAE, we hypothesise that participants with SAE in English-speaking countries will demonstrate better efficiency and balance in bidirectional word translation tasks compared to those without such experience.3.3.1.To ensure a homogenous sample, we only included participants who shared a similar linguistic and cultural background. All participants were native Chinese speakers, aged between 20 and 30, a criterion chosen based on existing research indicating the influence of age and cultural background on brain activity .As detailed in The study abroad (SA) group, consisted of 25 students, each enrolled in one of these three universities in Sydney, Australia . They had an average SAE duration of 3.64 years and an average age of 25. In their Australian academic environment, they typically engaged in interpreting and translation classes conducted mainly in English for 25–30 h weekly. While interactions with faculty and international peers were predominantly in English, they reverted to Chinese for conversations with fellow Chinese students.On the other hand, the non-study abroad (NSA) group was composed of 25 students from three universities in Xi’an, mainland China . These students had not ventured to English-speaking nations and had an average age of 24. Their curriculum consisted of approximately 28–30 h of interpreting and translation weekly. However, the teaching methodology leaned heavily on their native Chinese language, and their daily interactions seldom involved English.To further elucidate participants’ linguistic profiles, we utilised the Language Experience and Proficiency Questionnaire (LEAP-Q). Widely recognised in linguistic and psycholinguistic research e.g., , this to3.2.3.2.1.Participants’ working memory resource availability was assessed using the English reading span task , adminisUpon completion of each set, participants were prompted to recall as many sentence-final words as they could. No restrictions were imposed on the order or duration of the recall. Participants’ recalled final words were considered valid only if accompanied by accurate judgements regarding sentence plausibility. The number of correctly recalled final words served as an indicator of a participant’s working memory span.3.2.2.This study emphasises L2 proficiency due to the background of our participants. Being native Chinese speakers, their proficiency in their L1 is uniformly high and consistent for daily communication. In contrast, as English is their foreign language, their L2 proficiency is expected to vary. They were asked to complete LexTALE, a reliable and standardised online test of general English proficiency that is widely employed in linguistic studies e.g., . This as3.2.3.Participants’ lexical processing performances were assessed using word translation recognition tasks, administered via E-Prime Professional 2.0 and Chronos. Distinct versions of the word translation recognition task were employed for both language directions (English-Chinese and Chinese-English). The stimuli consisted of 60 English and 60 Chinese words, which were presented auditorily in a randomised order for each participant using E-Prime Professional 2.0. During each trial, participants listened to a word through headphones, and the correct translation equivalent or an incorrect, misleading word was displayed on the screen. Participants were instructed to rapidly and accurately identify whether the word on the screen corresponded to the correct translation of the auditorily presented word by pressing the Yes or No buttons on the Chronos box. No time limit was imposed on participants’ responses.Two word characteristics—word frequency and word length—were carefully controlled across stimuli and target translation equivalents in both translation directions (L1-L2 and L2-L1) to ensure the generalisability of our findings.Chinese and English word frequencies were obtained from the SUBTLEX-UK  and SUBTNonetheless, matching word length across Chinese and English is exceedingly challenging, given their typological distinctions as languages. This study only ensured that the Chinese words employed in both directions comprised a comparable number of characters, while the lengths of the English words utilised in the task were similarly consistent.Participants’ accuracy (%) and response times (ms) were calculated, with only the response times of accurate trials incorporated into the data analysis. Although translation has long been a conventional pedagogical task in L2 and interpreting training, employing a response time-based translation task as a research instrument remains relatively novel .3.2.4.To delve deeper into participants’ subjective experiences and cognitive reflections on lexical translation performance, we conducted a post-task interview. This complementary approach aimed to understand both their self-evaluations of the lexical translation and the underlying reasons for their perceptions.The interview served two primary purposes:Firstly, we provided a quantitative self-assessment, allowing participants to rate their performance on a five-point scale .Secondly, we sought qualitative insights through an open-ended question. This was designed to reveal the underlying factors or thought processes influencing their ratings, providing a deeper understanding of their performance beyond the quantitative assessment.All interviews were conducted in their native language to ensure comfort and clarity in communication.3.3.Participants consented to the research conducted in a quiet university space using a Lenovo laptop and E-Prime Professional 2.0 software. All verbal instructions were delivered in their native language. Tasks involved word translation recognition and reading span, with response times and accuracy recorded via a Chronos response box. The task order was counterbalanced to mitigate fatigue effects. The session, approximately 30 min, was audio-recorded. It included consent, LexTALE completion, memory span task, bidirectional word translation tasks, and a post-task interview.4.t(24) = 0.30, p = 0.77. and their L2 proficiency assessed by LexTALE, t(24) = 0.85, p = 0.41.Two groups were comparable in their mean working memory, 4.1.F = 35.02, p < 0.001, The impact of SAE on the groups’ bidirectional word translation was explored via a 2 × (2) mixed factorial ANOVA with the within-subjects factor of the direction of translation (L2-L1 vs. L1-L2) and the between-subjects factor of the group (NSA vs. SA). A significant main effect of direction was observed in accuracy, 4.1.1.F = 8.51, p = 0.005, According to the 2 × (2) mixed factorial ANOVA, a significant main effect of group was observed in the two groups’ accuracy, 4.1.2.F = 0.05, p = 0.83, According to the 2 × (2) mixed factorial ANOVA, the group × direction interaction was not significant in both groups’ accuracy, 4.2.p = 0.004, The impact of SAE on the groups’ bidirectional word translation was explored via a 2 × (2) mixed factorial ANOVA with the within-subjects factor of the direction of translation (L2-L1 vs. L1-L2) and the between-subjects factor of the group (NSA vs. SA). A significant main effect of direction was also observed in response times, F = 8.96, 4.2.1.p = 0.004, According to the 2 × (2) mixed factorial ANOVA, a significant main effect of group was observed in response times, F = 9.05, 4.2.2.F = 5.134, p = 0.028, t(24) = 4.17, p < 0.001. In contrast, no statistical difference was detected for the SA group, t(24) = 0.47, p = 0.64, which suggests a more balanced performance across the two language directions among the SA group.According to the 2 × (2) mixed factorial ANOVA, a significant group × direction interaction was observed in response times, 4.2.3.t(24) = 0.65, p = 0.52. This indicates that both groups perceived their performance as somewhere around ‘average’.Delving into the qualitative feedback from the open-ended question, a noteworthy pattern emerged. A substantial 17 out of 25 SA participants felt they had rushed through the task. They expressed a post-submission realisation of their errors, indicating a premature commitment to answers. One SA participant reported, ‘Although I thought the task would be challenging at first, I later found it to be less difficult than I had anticipated. Nevertheless, I still felt compelled to respond as quickly as possible, maybe due to some external pressure or personal drive’. In contrast, only 2 out of 25 NSA participants reported similar experiences, with most commenting on the difficulty of the task, such as confusing distractors that resembled the correct words.5.5.1.Based on the results presented in 5.2.As illustrated in What is noteworthy is the consistency of this direction-dependent asymmetry across both groups, regardless of their SAE. This consistency echoes findings by 5.3.A key differentiator between the two groups in this study is the SAE. The SA group demonstrated faster response times but lower accuracy in lexical translation compared to the NSA group, suggesting a speed-accuracy trade-off. To shed light on these observed differences, we integrated insights from post-task interviews and LEAP-Q results.5.3.1.Though self-ratings indicated similar self-perceptions of performance across both groups , qualita5.3.2.The SA group engaged more frequently with English speakers on a weekly basis than the NSA group. Given that regular L2 usage can bolster learners’ communicative willingness , SA partOur observations align with research by The potential role of cognitive control also merits attention. Previous research highlights the intricate relationship between language use experience and cognitive control abilities . Xie andIt is crucial to differentiate between working memory and cognitive control. While working memory manages information retention and manipulation, essential for tasks like language processing , cognitiIn this study’s context, both SA and NSA groups having similar working memory capacities suggests equivalent foundational cognitive capabilities. Yet, differences in their SAE could have uniquely moulded their cognitive control faculties. Regular immersion in L2, as experienced by the SA group, intensifies cognitive control demands due to continuous language switching, L1 inhibition, and tackling L2 challenges. Such immersion could have finetuned the SA group’s cognitive control, even if their working memory remained consistent with the NSA group.This variance may explain the observed differences in cognitive control between the two groups, despite comparable working memory capacities. It is not a claim of cognitive superiority but indicates that linguistic experiences might influence cognition differently. Future studies should delve deeper into this by evaluating working memory and cognitive control in comparable bilingual cohorts.5.4.The interaction effects in the context of accuracy and response times yielded contrasting insights. While there was no interaction effect for accuracy (indicating that both groups showed a similar pattern of direction-dependent asymmetry in accuracy), there was a significant interaction for response times. The NSA group displayed a notable difference in their response times for L1-L2 vs. L2-L1, whereas the SA group did not.These findings imply that having an SAE might lead to a more consistent and balanced performance in word translation across both language directions. In contrast, those without such an experience may face more variability in their translation speeds depending on the direction.Our findings replicate that of For the SA group, immersion in an L2-rich environment granted them a distinct advantage by allowing them to suppress interference from their dominant L1 more effectively e.g., . This reIt is well-established that prolonged exposure to bilingual environments sharpens a bilingual’s ability to switch languages e.g., . MoreoveIn contrast, for NSA participants in our study, their daily linguistic environment was predominantly aligned with their native L1. This might have heightened the challenge of suppressing the ever-present L1 during L2 processing, thus skewing their bilingual lexical translation. Moreover, their interactions in English were notably fewer than those of the SA group, as indicated by their LEAP-Q results. This suggests that they predominantly communicated in Chinese, especially with fellow Chinese students, limiting their opportunities for smooth transitions between languages. The absence of a consistent L2-rich environment might deprive the NSA group of the routine that aids mental set shifting, especially the transition between languages. Consequently, this might lead to a pronounced degree of asymmetry in the NSA group’s performance.Furthermore, it is pertinent to underscore the unique linguistic profile of interpreting students. As trainees navigating two languages on a daily basis, they embody a distinct category of bilinguals. Language switching is integral to their training, sharpening their ability to transition between languages rapidly. Even amidst this frequent toggling, the impact of SAE on lexical processing emerged prominently in our findings. Such a pronounced effect, in spite of their rigorous linguistic exercises as interpreting students, further underscores the profound influence of SAE. It suggests that while routine interpreting practices equip students with certain bilingual proficiencies and cognitive advantages, immersion in an authentic language environment through SAE offers unparalleled benefits.To wrap up our discussion, our findings indicate that concerning direction-dependent asymmetry, both SA and NSA groups were more adept in translating words from L2 to L1 than vice versa. Although we postulated that the SA group showcased more efficient bidirectional word translation, the results were multifaceted. While the SA participants were faster across translation directions, the NSA group exhibited greater accuracy. This divergence hints at a speed-accuracy trade-off: SA participants, due to their extensive L2 usage and frequent language toggling, might prioritise speed and a propensity to communicate, even without the precise word.Moreover, our research underlines that SAE aids in achieving a less asymmetric performance in word translations across languages. Such observations emphasise the instrumental role of SAE in alleviating language competition, diminishing the cognitive strain tied to bilingual lexical processing, and fine-tuning the cognitive mechanism managing bilingualism.This study is not without its limitations, notably its cross-sectional design. Adopting a longitudinal methodology, tracking the same group of students during their SAE might offer richer insights into the progression of their lexical translation performance.Additionally, we assessed only the overarching working memory resources, bypassing specific facets of cognitive control. Prospective research should delve into this, appraising both working memory and cognitive control in comparable bilingual groups.Lastly, the SAE is a composite of linguistic immersion and the intricacies of residing in a foreign country. While our participants’ increased willingness to communicate might arise from intensified linguistic exposure and interaction in a study-abroad context, it could also be shaped by non-linguistic elements like the process of cultural adaptation. As 6.This study elucidates the impact of SAE on bidirectional lexical translation among Chinese (L1) English interpreting students. While previous research has touched upon the effects of SAE on bilingual translation, our findings augment this body of knowledge by highlighting the performance differences between the SA and NSA groups. Notably, the SA group showcased superior consistency in their translations and displayed heightened communicative willingness.Recognising the crucial role of lexical processing in higher-order language processing, including interpreting, there’s an evident need for pedagogical adjustments. We advocate for universities to bolster communicative activities both within and beyond the curriculum, thereby immersing students more deeply in their L2. Such active engagement can potentiate the activation of their L2, mitigating the cognitive burdens of L2 processing and language switching. This approach bears significant relevance for interpreting learners, aiding them in honing critical skills for their academic and future professional endeavours.While numerous studies have delved into bilingualism across varied language-learning contexts, there remains a paucity of research focusing on the SAE’s impact on the Chinese-English language pairs, especially among interpreting students. As such, our results not only bridge this gap but also furnish actionable insights for L2 educators and interpreting trainers. The findings are especially pertinent for interpreting students without the advantage of SAE, offering them strategies to compensate for their limited interactions in L2 environments.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving humans were approved and conducted by Western Sydney University Human Research Ethics Committee’s guidelines . The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.RW: Conceptualization, Data curation, Formal Analysis, Investigation, Writing – original draft, Writing – review & editing. JH: Supervision, Writing – review & editing. BB: Supervision, Writing – review & editing. MA: Data curation, Formal Analysis, Software, Supervision, Writing – review & editing.


The complex and highly variable three-dimensional anatomy of the left atrial appendage (LAA) makes planning and device sizing for interventional occlusion procedures (LAAC) challenging. Several imaging modalities  are used for this purpose. Virtual reality (VR) is an emerging imaging technique to immerse into a three-dimensional left atrium and appendage, offering unprecedented options of visualization and measurement. This study aimed to investigate the feasibility, accuracy and reproducibility of visualizing the LAA in VR for preprocedural planning of LAAC.r = 0.93), max. (r = 0.80) and mean  diameters as well as landing zone (LZ) min. (r = 0.84), max. (r = 0.86) and mean diameters  showed strong correlations. Three-dimensional orientation was judged superior by physicians in VR compared to MSCT (p < 0.05).Twenty-one patients  who underwent LAAC at University Hospital Düsseldorf were included in our study. A dedicated software generated three-dimensional VR models from preprocedural MSCT imaging data. Conventional measurements of LAA dimensions  using a commercially available software were compared to measurements in VR: MSCT and VR ostium min. (Virtual reality visualization of the left atrium and appendage based on MSCT data is feasible and allows precise and reproducible measurements in planning of LAA occlusion procedures with enhanced 3D orientation. Further studies need to explore additional benefits of three-dimensional visualization for operators in preprocedural planning. Application of VR for LAA sizing: 21 patients with preprocedural MSCT and intraprocedural TEE were included. LAA measurements performed in the virtual environment showed strong correlation with current gold standard MSCT and were highly reproducible. In addition, VR offered a superior spatial orientation and depth perception. LAA, left atrial appendage; LAAC, left atrial appendage closure; MSCT, multi-slice computed tomography; TEE, transesophageal echocardiography; VR, virtual reality; LZ, landing zone. Advances in multimodal imaging have been a cornerstone for the evolution of minimally invasive interventional procedures . VirtualLAAC has emerged as a safe and efficient treatment option for stroke prevention in multimorbid patients , 6. The The aim of our study was to evaluate the feasibility and accuracy of LAA measurements in VR for device sizing in patients undergoing LAAC.™ occluder device under conscious sedation and with intraprocedural guidance using TEE and fluoroscopy. All imaging data were retrospectively analyzed. The study was approved by the local ethics committee (no. 5272R) and complies with the declaration of Helsinki.From June 2019 to October 2021, all patients with non-valvular atrial fibrillation who underwent LAAC and preprocedural MSCT at University Hospital Düsseldorf were included. All patients received an Amulet Amplatzer™, Pie Medical Imaging BV, Maastricht, The Netherlands). All datasets were evaluated, and measurements performed by an independent physician highly experienced in this modality. Image quality was defined as insufficient in case of inadequate delineation of the endocardial border due to incomplete contrast opacification of the LAA. Furthermore we assessed data set regarding slow flow, sludge or LAA thrombus. In detail, the LAA was analyzed by semi-automated 3mensio LAA workflow. The left circumflex coronary artery and the coumadin ridge were marked and defined the ostium. The landing zone (LZ) was defined at a location 10–12 mm distal from the ostium after adjusting the angle. The depth was measured as a perpendicular line from the ostium to the LAA roof.All patients underwent pre-procedural high-resolution, contrast-enhanced, electrocardiogram-gated spiral acquisition mode CT . Images were obtained at 30%–60% of the R-R interval. A delayed scan after contrast injection was used to allow optimal contrast distribution according to established protocols. Images were taken in accordance with LAA-specific expert recommendations on CT acquisition . All datIntraprocedural TEE was performed for guidance of the procedure. All TEE studies were performed under conscious sedation by an advanced imaging cardiologist using an EPIQ 7 ultrasound machine and an X8-2T TEE probe , as described previously . The LAAThe Meta Quest 2  VR headset was employed for visualization in VR with Single Fast-Switch LCD display and a resolution of 1,832 × 1,920 pixels per eye with a refresh rate of 72 Hz. Visualization in VR was done using dedicated software  based on MSCT imaging data (DICOM datasets). The software allowed anatomical visualization, including free navigation  through the virtual heart. Steering the 3D model was enabled with two handheld controllers allowing to zoom, grab, slice, cut out and rotate the model. Distance measurements were directly performed in the VR environment in the same cardiac cycle as measurements in MSCT.The protocol for measurements in VR is displayed in t-test was applied to compare continuous variables. The agreement of MSCT and VR measurements were displayed with Bland-Altman plots. The correlation of MSCT and VR measurements were calculated using Pearson's correlation coefficient. P-values < 0.05 were considered statistically significant. All measurements were performed using GraphPad Prism version 9 .Continuous variables are displayed as counts and percentages and mean ± standard deviation. The dataset was tested for normal distribution using the D’Agostino-Pearson normality test. Unpaired All measurements were conducted independently by two experienced imaging specialists to analyse interobserver variability. Inter- and intraobserver variability for VR measurements were calculated using the ICC. One of the investigators repeated the measurements of 10 Patients 3 months after the initial measurement in VR to analyse intraobserver variability. Inter- and intraobserver agreement was considered excellent, good, moderate and poor for ICC >0.90, 0.75–0.90, 0.50–0.75 and <0.50 respectively. The calculation of the intraclass correlation coefficient (ICC) was performed with SPSS .A total of 21 patients were included in our study. The mean age was 78.5 years (IQR: 74.5–82.3 years). Thirteen patients (62%) were male. Four patients were excluded due to insufficient MSCT image quality. Image quality was defined as insufficient in case of inadequate delineation of the endocardial border due to incomplete contrast opacification of the LAA. This was evaluated by two independent cardiologists. None of the patients included showed slow flow, sludge or LAA thrombus in TEE or MSCT. All patients underwent LAAC with the Amplatzer Amule™ Occluder, 9.5% of patients received an 18 mm occluder, 4.8% a 20 mm occluder, 23.8% a 22 mm occluder, 42.9% a 25 mm and 19% a 28 mm occluder. Overall, few complications occurred in our study cohort. One patient developed arrhythmia, two patients had major and three patients suffered from minor bleedings. No device related complications such as thrombus, device dislocation or pericardial effusion were observed. Further detailed baseline characteristics are displayed in p = <0.001). Likewise, at the level of the LZ, no significant difference was observed between MSCT (22.0 ± 3.1 mm) and VR measurements , whereas 2D-TEE derived dimensions were significantly smaller . Lastly, for the LAA depth, no significant difference was observed between MSCT (20.3 ± 4.5 mm), VR (21.6 ± 4.7 mm) and 92D TEE , maximum diameter  and mean ostium diameter . Furthermore, good to excellent correlation was observed at the level of the LZ with the LZ minimum diameter , LZ maximum diameter  and LZ mean diameter . The measurement of the LAA depth showed moderate correlation . However, we observed a lower correlation in chicken-wing morphology of the LAA (r = 0.63) compared to non-chicken-wing configuration (r = 0.87). Comparison of mean ostium dimensions between MSCT (29.5 ± 3.2 mm) and VR (29.7 ± 4.1 mm) did not show a significant difference, while measurements in 2D-TEE significantly underestimated ostium diameters ] to MSCT [Median 3 (IQR 2–3), The main findings of our study are as follows: First, DICOM MSCT imaging data can reliably be visualized in VR. Second, LAA measurements in VR are well correlated to the gold standard MSCT with additional benefit in orientation in the 3D surrounding. Third, measurements in VR showed a high inter- and intraoperator reproducibility.LAAC is a well-established, safe and effective procedure for stroke prevention in patients with non-valvular AF. Accurate measurements of LAA dimensions are crucial for an optimal device sizing to prevent complications. Numerous comparative studies have shown advantages of MSCT-based LAA sizing and device selection compared to TEE or fluoroscopy. Saw et al. for instance showed a good correlation of ostium and LZ maximal diameter measurements among TEE, MSCT and fluoroscopy, with MSCT providing the largest diameters for ostium and LZ . 2D TEE . demonstrated the applicability of real-time live 3D TEE and 3D rotational angiography during cardiovascular procedures  and complication rates. Since no device related complications occurred in the present study, the hypothetical impact of sizing in VR on these complications could not be analyzed. This should be addressed in further studies. Also, only patients with uncomplicated and completed LAAC were included and patients unsuitable for LAAC were not considered. All included patients received an Amulet AmplatzerVirtual reality visualization of the left atrium and appendage based on multislice CT data is feasible and allows precise and reproducible measurements in planning of occlusion procedures. Thus, VR offers the benefits of a true 3D visualization with superior depth perception without having to compromise on the precision of the measurements. However, further studies need to explore additional benefits of three-dimensional visualization for operators in preprocedural planning.


Chronic critically ill patients (CCI) in pediatric intensive care unit (PICU) are at risk of negative health outcomes, and account for a considerable amount of ICU resources. This study aimed to (a) describe the prevalence of CCI children, (b) compare their clinical characteristics and ICU resources use with non-CCI children, and (c) identify associated risk factors of CCI.A retrospective national registry study including 2015–2017 data from the eight Swiss PICUs of five tertiary and three regional hospitals, admitting a broad case-mix of medical and surgical patients, including pre- and full-term infants. CCI patients were identified using an adapted definition: PICU length of stay (LOS) ≥8 days and dependence on ≥1 PICU technology.p < 0.001). Nursing workload was higher in the CCI compared to the non-CCI group . Factors associated with CCI were cardiac (aOR = 2.241) and neurological diagnosis (aOR = 2.062), surgery (aORs between 1.662 and 2.391), ventilation support (aOR = 2.278), high mortality risk (aOR = 1.074) and agitation (aOR = 1.867).Out of the 12,375 PICU admissions, 982 (8%) were CCI children and compared to non-CCI children, they were younger (2.8 vs. 6.7 months), had more cardiac conditions (24% vs. 12%), and higher mortality rate (7% vs. 2%) (the results confirm the clinical vulnerability and the complexity of care of CCI children as they were defined in our study. Early identification and adequate staffing is required to provide appropriate and good quality care. PatiEarly identification of CCI children is essential to plan individualized care, with the goal of optimizing long-term patient outcomes. Traditionally, these children were identified using PICU LOS only. However, a definition that includes clinical complexity criteria in addition to a PICU LOS may be more appropriate , 15, esp2.This study followed the Strengthening the Reporting of Observational Studies in Epidemiology reporting guidelines for cross-sectional studies . The research protocol was approved by the Human Research Ethics Committees in Switzerland . Participants consent was waived, as data were anonymous.2.1.We performed a retrospective observational study of PICU hospitalizations between January 1, 2015 and December 31, 2017. Data were extracted from the administrative and clinical records of the Minimal Dataset of the Swiss Society of Intensive Care Medicine (SSMI), including data from the eight mixed PICUs/NICUs in Switzerland, five of them being from a tertiary referral hospital, and three from a regional hospital. Altogether, they account for 100 beds and approximately 5’000 annual admissions. They admit a broad case-mix including medical and surgical patients, as well as full-term and preterm infants.2.2.–Pediatric CCI (PCCI): from 1 month to 18 years, PICU LOS of ≥8 consecutive days, and ongoing technology and healthcare resource use–Neonatal CCI (NCCI): ≤37 weeks gestational age, PICU LOS of ≥8 consecutive days postterm corrected age, and ongoing technology and healthcare resource useCCI children were identified according to the following definition adapted from , 15 Fig:–PediatNon-CCI children were children who did not meet the CCI criteria.Exclusion criteria for CCI and non-CCI children: >18 years of age, transfers from another PICU.Life-sustaining technology dependence was defined as per Shapiro’s definition and the criteria of the Swiss Society of Intensive Care Medicine to define technology, as follows: ongoing requirement of ≥1 of the following (a) invasive or non-invasive ventilation, or other ventilation ; (b) intravenous (IV) medications ; (c) dialysis; (d) Extracorporeal Membrane Oxygenation therapy (ECMO) .Children were identified as CCI at PICU day 8 and were considered CCI until discharge, regardless of their requirement of life-sustaining technology throughout their remaining PICU stay.2.3.The demographic and clinical characteristics extracted from the dataset included: age, sex, PICU LOS, unplanned PICU admissions, PICU readmissions within 48 h, principal diagnosis, surgical interventions, mortality risk score, provenance before PICU admission and destination after PICU discharge, mortality in PICU, and therapeutic limitations .PICU resources use included nursing workload, patient’s agitation status, PICU technologies and healthcare resources use. Nursing workload was measured using the validated Nine Equivalents of Nursing Manpower use Score (NEMS), including the following items, basic monitoring, intravenous medication, mechanical ventilation, supplementary ventilator care, single and multiple vasoactive medication, dialysis, and specific intervention in the ICU and outside the ICU . NEMS’ s2.4.r > 0.6). Descriptive statistics were used to describe demographic and clinical characteristics of patients, and their PICU resource use. Categorical variables were summarized using frequency and percentage, and continuous variables using median and interquartile range. CCI and non-CCI groups were compared with Fisher’s exact test  and Wilcoxon’s test (continuous data). Level of significance was two-sided α = 0.05. We performed bivariable and multivariable logistic regression models to identify the risk factors of CCI group, adjusted by centers. A conservative significance level of p = 0.20 was used to keep the variables in the multivariable model . Because they were only documented when therapeutic limitation was indicated, they were treated as not applicable. No collinearity among variables was found , transferred from another PICU n = 325 (3%)). In total 12’375 PICU hospitalizations were analyzed, including 982 (8%) CCI children. Most of them was PCCI (87%). Demographic and clinical characteristics of the sample are presented in p < 0.001); 42% of them having a PICU LOS ≥14 days. CCI children compared to non-CCI were significantly younger, , and had more unplanned PICU admissions . Provenance and destination after discharge were significantly different between the CCI and non-CCI groups (p < 0.001). More patients from the non-CCI group were admitted from the operating room than patients from the CCI group , and these latter were discharged to the ward less often than non-CCI patients . The principal diagnosis was significantly different between CCI and non-CCI groups (p < 0.001). Cardiac diagnoses were twice as frequent in the CCI group  as in the non-CCI group . Type of surgical interventions was significantly different between CCI and non-CCI groups (p < 0.001). Nearly half of CCI children had cardiac surgery (47%) vs. 26% in non CCI. Mortality risk of CCI children who were less than 16 years old (PIM2) was significantly higher than non-CCI children of the same age [Mdn = 3.2 (1.5–9)] vs. 1.6 [0.6–3.4] respectively, p = <0.001). PICU mortality in the CCI group was 7% (n = 62), compared to 2% in the non-CCI group (n = 225) (p < 0.001). Use of therapeutic limitations in the CCI group (3%) was higher than the non-CCI group (0.2%) (p < 0.001). Withholding treatment was more frequently used in non-CCI compared to CCI patients , while withdrawal of life-sustaining interventions was more widely adopted for the CCI patients compared to non-CCI patients .We identified 12,736 admissions; 361 were excluded (>18 years 3.2.p < 0.001). CCI children experience more episodes of agitation (SAS score ≥5) per day than non-CCI . Frequency and duration of utilization of PICU technologies were all statistically higher in the CCI group compared to non-CCI (p < 0.001). The proportion of isolation as an indicator of resources use was higher in CCI children compared to non-CCI .The PICU resources use in both groups of CCI and non-CCI children are presented in 3.3.Risk factors of CCI in PICU children derived from the bivariate analysis resulted in eight variables included in the multivariate analysis: principal diagnosis, surgical interventions, standardized mortality risk score, ventilation support, type of PICU admissions, therapeutic limitations, agitation status and total NEMS. Results are shown in 4.This retrospective national registry study is the first to report clinical characteristics and PICU resource use of CCI children, using a definition that includes both temporal and complexity criteria in a mixed PICU population in Switzerland. Key findings related to the prevalence rate for CCI children in PICU, the clinical characteristics and PICU resources needed of CCI children in the Swiss PICUs, and risk factors of CCI are discussed below.Our CCI prevalence rate of 8% is relatively low, but sits within the reported prevalence range 6% to 14%) of long-stay patients (≥14 days) % of long. Our defThe majority of the CCI clinical characteristics are similar to those reported in other studies with prolonged PICU LOS samples. CCI children in our study are young (median age <3 months) and have more cardiac conditions and surgeries than non-CCI children. Similar results were reported in other studies, with younger age (<12 months) being significant  and specCCI children in our sample had significantly higher risk of mortality compared to non-CCI. This result is not surprising considering the need for life-sustaining treatment for a prolonged period. Other studies reported comparable findings with mortality rates ranging between 8% and 20% in CCI patients with a PICU LOS greater than 14 days . Our stup < 0.001), vasoactive support , extracorporeal life support  and renal replacement therapy , respectively (Our results also show that CCI children use a higher proportion of PICU resources than non CCI, which is consistent with international findings demonstrating a higher use of resources in CCI patients independent of the PICU LOS threshold used , 10, 27.ectively . As CCI Risk factors for becoming a CCI child identified in our sample correspond with previous studies , 29. AltThere are several limitations to this study. First, our results based on a Swiss data may not be generalized to CCI children from other countries, in which healthcare system delivery differ greatly based on Swiss data. Nevertheless, most of our findings were comparable to the literature from other Western countries adding to the validity of our results. Second, we were unable to identify children with repeated hospitalizations, also considered as CCI. It is thus possible that in our study, the reported number of CCI children is lower than the current reported prevalence rate of CCI children in Switzerland. Third, variables such as discharge with a device or a continuous infusion of a drug treatment as well as comorbidities, which would have been useful for the association with CCI development were not currently recorded in the national registry . Fourth,5.Our study provides additional evidence highlighting the importance to consider CCI children being a central part of PICUs, given their specific characteristics and high resource needs when compared to non-CCI. It is, therefore, imperative for healthcare systems to adapt their model of care to best meet the specific needs of CCI children. Multidisciplinary PICU teams need to pay particular attention on the development and test early interventions to promote physical, cognitive, emotional, and social health of CCI children. The prevention of adverse events to enhance their QOL after PICU, and implementation research on patient- and family-centered care approach are necessary. Additional work is needed to understand which interventions during or following hospitalization reduce healthcare use with special attention to CCI children.