Soft tissue sarcoma is a relatively rare entity that comprises heterogeneous types of tumors. Here we report the case of a 14-year-old girl with pelvic sarcoma with a YWHAE-NUTM2B fusion gene. This fusion transcript has been reported in endometrial stromal sarcomas and clear cell renal sarcomas, but its description in pelvic sarcomas is recent. To our knowledge, this is the first case report describing this translocation in an adolescent patient with soft tissue sarcoma. The patient underwent cytoreductive surgery, followed by systemic chemotherapy and targeted drug treatment. Surprisingly, the treatment was effective, and the young patient is being followed up in our department. Soft tissue sarcomas (STSs) are a heterogeneous group of malignant tumors arising from mesenchymal cells, which are proportionally more common in children and adolescents . The higIn general, treatment for sarcoma patients involves surgery, chemotherapy, radiotherapy, or a combination thereof. For metastatic or advanced STS patients, doxorubicin alone or combined with other cytotoxic drugs has been traditionally recommended as the first-line treatment in the last four decades . A deep This clinical case reports the discovery and management of an adolescent presenting abdominal and pelvic sarcoma with a YWHAE-NUTM2B fusion gene, which has been previously described in clear cell sarcoma of the kidney (CCSK) and high-grade endometrial stromal sarcoma (HGESS) , 6. It hReviewing the literature, we found very few cases of sarcoma with a YWHAE-NUTM2B fusion gene in adolescents, and we have not identified any clear treatment strategy. The aim of the case report is to draw attention to the diagnosis and clinical treatment of this rare but severe sarcoma entity. Our case is interesting for three reasons: the young age of the patient, the extremely progressive development of the tumor, and the effective treatment of combined chemotherapy of epirubicin with anlotinib.A 14-year-old girl was admitted on September 18, 2021, to the Department of Obstetrics and Gynecology, the Third Affiliated Hospital of Soochow University, Changzhou, China, for moderate, persistent pelvic diffuse pain in order to establish therapeutic specialist conduct. She is a non-smoker and has no history of contraceptive use, has irregular and moderate menstrual cycles, has occasional dysmenorrhea, has no other significant diseases, and has no important medical family history. A huge mass was accessible, reaching the xiphoid process superiorly, and the uterine adnexa was poorly palpated by pelvic examination. Ultrasound suggested a huge abdominal mass. A CT scan of the whole abdomen suggested a huge space occupying the abdominopelvic cavity, blurred surrounding intestinal fat spaces, retroperitoneum multiple enlarged lymph nodes, and unclear double adnexal areas. The tumor marker carbohydrate antigen (CA) 125 was 920.20 U/ml. After informed consent was obtained, exploratory surgery through laparotomy was performed under general anesthesia in our hospital. Specifically, she had right adnexectomy, omentectomy, peritoneal lesion resection, mesenteric lesion resection, and pelvic adhesiolysis. The pelvic cavity was filled with lobulated sarcomatoid tissue, with no obvious envelope. A lobulated sarcomatoid tumor attachment measuring approximately 15 × 15 × 6 cm was seen on the left lateral peritoneal surface. The surface of the omentum was full of lobulated sarcomatoid tissue and measured about 30 × 20 × 20 cm in size. Lobulated sarcomatoid tissue, approximately 8 × 7 × 6 cm to 6 × 5 × 4 cm in size, was found on the intestinal surface and intraperitoneally on the right side of the pelvic cavity, respectively. The uterus was posteriorly positioned, of normal size, smooth, and mobile. The fallopian tube of the left ovary was of normal size and has a smooth surface. The right ovary was slightly enlarged, with edema of the surface and a sarcomatoid tissue attachment on the surface. During the operation, the right ovary was cut, and it was seen that the right ovary was full of sarcomatoid tissue, and the right fallopian tube showed no abnormalities. Scattered masses of about 6 × 5 × 5 cm to 4 × 3 × 3 cm in size were found in the uterine rectal fossa and rectal surface with irregular morphology. The liver surface was smooth, there were no masses in the stomach and diaphragm, and the retroperitoneal lymph nodes were widely enlarged. Postoperative pathology showed neoplastic lesions (right appendix), which tended to be malignant; the type was difficult to determine. No tumor involvement was seen in the ipsilateral fallopian tube. Abdominal wall nodule, intestinal surface nodule, pelvic nodule, greater omentum nodule, and pelvic mass were considered malignant tumors, while the specific type was difficult to determine.H&E shows these tumor cells are made of small round cells, with scanty eosinophilic cytoplasm and a hyperchromatic nucleus  showed abdominal and pelvic lesions, blurred surrounding intestinal fat space, and multiple enlarged lymph nodes behind the peritoneum, which were similar to previous findings . Abdominal and pelvic effusions were more advanced than before, and the chest CT scan showed right pleural effusion with atelectasis, right pulmonary nodule, and possible metastasis  count 2.84 × 10Considering the rapid progression of the malignancy, we decided to start the treatment immediately after the improvement of the patient’s general condition. On day 5, she was given antitumor therapy with the consent of her parents. The chemotherapy regimen was as follows: epirubicin 40 mg on days 1 and 2 combined with anlotinib  8 mg/day targeted therapy. The patient was concomitantly treated with suppression of vomiting. The patient’s symptoms of abdominal distension and chest tightness improved after comprehensive treatment. On day 13, the patient was discharged with a better general condition. On November 15, 2021; December 7 and 30, 2021; January 21, 2022; February 21, 2022; March 15, 2022; and April 13, 2022, the patient received epirubicin 40 mg on days 1 and 2 combined with anlotinib 8 mg orally per day. After only 2 courses, the tumor decreased dramatically. CA125, an important ovarian cancer-associated antigen, decreased significantly to 125.40 U/ml as compared to the previous value of 920.20 U/ml. The latest value of CA125 was already decreased to normal (16.0 U/ml) Figure 3In the current study, we presented a case of rare pelvic sarcoma harboring the YWHAE-NUTM2B/E fusion transcript in a 14-year-old patient. YWHAE gene belongs to the 14-3-3 family of proteins, which mediate various biological functions, including cell proliferation, differentiation, and metabolism . NUTM2B There are little data about stromal sarcoma’s origin and biology. Histopathological diagnosis is very important for prognosis. However, it is difficult by conventional pathologic means to definitively diagnose soft tissue tumors that require NGS testing. With the wide application of NGS, an increasing number of novel genetic abnormalities in undifferentiated round cell sarcomas have been identified, including BCOR-CCNB3/ZC3H7B/MAML3, CIC-DUX4/FOXO4, YWHAE-NUTM2B gene fusions, or BCOR internal tandem duplication . Both YWIn the present case, the main and only complaint was abdominopelvic pain; abnormal vaginal bleeding was not recorded. When the patient was admitted to our hospital, her condition was already advanced. Diagnosis of such cases adolescents is not a simple procedure. The tumor mass presented rapid growth, and 34 days after the surgery, the control CT scan showed a huge mass again in the abdominopelvic cavity with repression of the rectum. Due to the lack of knowledge of the fusion transcript, the young patient was diagnosed with “pelvic sarcoma with YWHAE-NUTM2B fusion gene” approximately 1 month after the surgery. It was difficult to confirm the origin of the tumor. There was an urgent need for systematic antitumor therapy due to the rapid growth of the tumor. We therefore developed a therapeutic strategy mainly based on the tumor histology and genetic diagnosis, despite the initial tumor origin.2 given on days 1 and 2 and anlotinib 8 mg once daily on days 1–14 of each 21-day cycle), the CT showed dramatic tumor regression.Due to the extreme rarity of YWHAE-NUTM2B fusion-positive STS in the clinic, currently, no standard therapeutic guidelines are available. The first-line treatment for STS is mainly based on anthracyclines and ifosfamide. Hopefully, there are gradually multiple targeted drugs showing therapeutic effects in STS, bringing clinical benefits to various histotypes of STS . Among tThis clinical report leads us to consider not only age and histology in adolescent sarcomas management but also the molecular analyses and genetic diagnosis to develop the therapeutic strategy. Due to the rarity of this pathology, it is difficult to complete randomized clinical trials to determine the optimal management of the tumor.STSs are a rare group of tumors that originate from connective tissues. The diagnosis is established by histopathology, extended IHC staining, and molecular tests such as NGS. Rapid diagnosis and timely surgical intervention must be a therapeutic standard in these cases. Traditional chemotherapy for STS is mainly based on anthracyclines and ifosfamide. In front of this complex and highly aggressive YWHAE-NUTM2B fusion-positive STS, we underline its clinical presentation . We propose the early combined therapy of epirubicin with anlotinib in case of such high-grade sarcomas with Eastern Cooperative Oncology Group (ECOG) scores greater than 2. A meta-analysis from large clinical trials is necessary to determine the prognosis and proper curable treatment of sarcoma with YWHAE-NUTM2B fusion.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Written informed consent was obtained from the individual(s), and minor(s)’ legal guardian/next of kin, for the publication of any potentially identifiable images or data included in this article.JH analyzed the data and drafted the manuscript. JH, YX, and JZ contributed to the conception of the case report. JH and JZ contributed significantly to the analysis and manuscript preparation. DZ helped analyze the pathological data. XN and JZ assisted in drafting the manuscript and critically reviewed the manuscript with regard to oncological issues and constructive discussions. All authors had final approval of the submitted and published versions.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 aims at investigating the anthropometric status and food consumption patterns of children in the United Arab Emirates (UAE) and assessing their adherence to nutrient and dietary recommendations. It is a population-based cross-sectional survey of 690 children (4–12.9 years), from 3 major Emirates. Socio-demographic and anthropometric characteristics were collected. Dietary intakes were assessed using the 24-hour recall approach. Of the total sample, 4% were stunted, 8% were wasted and 28% were overweight/obese. A third of participating children consumed above the Estimated Energy Requirement, while the majority’s intakes carbohydrate, total fat, and protein were within the recommendations; whereas over 70% and 90% of participants consumed above the WHO daily limits of free sugars and saturated fats, respectively. Inadequate intakes of linoleic acid (36% of children), alpha-linolenic acid (91%) and dietary fiber (100%) were observed. All children failed to meet the recommendation for vitamin D and considerable proportions had inadequate intakes of vitamin A, calcium, zinc, folate, and magnesium. Compared with the American Heart Association/American Academy of Pediatrics recommendations, low dietary adherence was noted for fruits (9%), vegetables (4%), and milk/dairy (14%). These findings may be used in the development of nutritional policies aimed at improving the diets of children in the UAE. The healthy eating and proper nutrient intakes in childhood are fundamental for optimal growth, development, and disease prevention ,2. Poor In addition to the high burden of NCDs, the MENA region harbors a double burden of malnutrition with stunting, wasting, and micronutrient deficiencies coexisting with overweight and obesity. The region has in fact been ranked second in the world for obesity prevalence rates . At the The age groups that are amongst the most vulnerable to all forms of malnutrition are children and adolescents . In factThe UAE is a Gulf country located in the MENA region which has flourished economically and demographically and undergone significant urbanization. Twelve percent of its population are nationals, and the remaining are expats of Arab and non-Arab origin. Eighty five percent of its national and non-national population are concentrated in the UAE’s three largest emirates  with approximately 15% of the total population aged between 0–14 years . The UAEDespite the growing interest and evidence framing childhood to be a time of unique nutritional needs, developmental plasticity and a critical window for optimal growth and development, limited population-based studies are available on malnutrition and dietary habits of the pediatric population in the UAE. It is in this context that this study was undertaken with the objectives of investigating the anthropometric status and food consumption patterns of children aged 4–12.9 years in the UAE and assessing their adherence to nutrient and dietary intake recommendations. The study focused on national and Arab non-national children in three major Emirates in the UAE: Abu Dhabi, Dubai, and Sharjah.n = 690; n = 461 nationals; n = 229 non-nationals), in compliance with the Kids Nutrition and Health Study (KNHS). The KNHS study is a large-scale cross-sectional survey aimed at investigating food consumption patterns, dietary intakes and food sources of nutrients in children [This study assessed the anthropometric status, dietary intakes, and food consumption patterns of a cross-sectional sample of children living in the UAE  constituted the various strata. Schools, which constituted the clusters, were randomly selected. Within the schools all children meeting the inclusion criteria were invited to participate. Details about the sam-pling are described elsewhere .For the UAE nationals, the calculation of sample size was based on an estimated obesity prevalence of 17%  with a 9A total of 690 children between the ages of 4 and 12.9 years were recruited from preschools and schools between June 2019 and March 2020. The study sample consisted of 461 national participants and 229 Arab non-nationals. To be eligible for participation in the study, children had to be aged between 4 and 12.9 years, without suffering from inborn errors of metabolism, chronic illness, or physical disability that could affect their eating patterns or anthropometric status. Arab non-nationals who have lived in the UAE for less than 3 years or those with mothers aged less than 18 years were excluded. Living in the UAE for a duration long enough (three years) was deemed necessary so that the children’s dietary intake reflects the country’s dietary habits.Data collection was conducted in Arabic, by research nutritionists who had participated in an extensive training in anthropometric measurement ,23, dietAnthropometric measurements (height and weight) were gathered for all study participants using standardized protocols ,23 and wDietary intake data were collected via the 24-hour recall (24-HR) method, using the multiple pass 5-Step approach that was developed by the United States Department of Agriculture . For porDietary data analysis was performed using the Nutritionist Pro Software . Based on local recipes, traditional UAE dishes were entered into the software, as single food items. The food composition databases that were utilized for dietary intake analysis included the USDA database, and the food composition tables for the Middle East , in addiTo characterize the population’s food consumption patterns, food items, as consumed, were classified into the following 10 groups: grains and grain products, fruits, vegetables, milk and milk products, meats and other protein sources, mixed dishes, savory snacks, sweets and sweetened beverages, fats and oils, and lastly, condiments and sauces. An overview of the groups and the food items within each group is shown in To further assess adherence of the study sample to the dietary recommendations of the American Heart Association/American Academy of Pediatrics (AHA/AAP) , all recFor analysis purposes, the sample was stratified into the following two age groups in accordance with the KNHS protocol: 4–8.9 years and 9–12.9 years.p < 0.05. All categorical variables, such as anthropometric and sociodemographic characteristics, were analyzed using percentages and frequencies, while means ± standard errors (SE) were used to describe continuous variables. Chi-squared (χ2) test was selected to test for statistically significant differences among categorical variables, whereas an independent t-test was selected for the continuous ones.Data analysis was performed with the Statistical Package for Social Sciences Software  using a significance level of The monthly income and the crowding index, which is defined as the total number of house occupants divided by the number of habitable rooms, were used to assess the socioeconomic status of participants. The crowding index identifies an index > 1, that is more than one person per room, as a crowded household with few economic resources .The percentage of participants adhering to the food group recommendations of AHA/AAP was computed and the Chi-squared test was then used to inspect the statistical differences between age groups. Total children’s energy intakes were compared with the age and sex-specific estimated energy requirements (EER) as published by the Institute of Medicine (IOM) . The usup < 0.001). In addition, a significantly higher proportion of children aged 9–12.9 years were obese (21%), as compared to the younger age group (10%) (p < 0.001). Although a higher proportion of 9–12.9 year-old children were stunted (5.0%) when compared to children aged 4–8.9 years (3.8%), these differences did not reach significance.The anthropometric characteristics of the study participants are shown in Food items, as consumed by the study participants, were categorized into 10 food groups. As for differences between nationals and Arab non-nationals, a significantly greater proportion of nationals adhered to the recommended servings of grains in comparison to non-nationals (75% vs. 63%), while a significantly lower proportion adhered to fruit recommendations .p < 0.001). Significant differences were observed between nationals and non-nationals whereby a higher percentage of nationals had their energy intake above EER (33.2%) compared to non-nationals (23.8%) (p = 0.012).Energy, macronutrient, and micronutrient intakes of the study sample and their DRI compliance are presented in Total fat consumption was within the ADMR for the majority of the sample, whereas 90% exceeded the maximum WHO recommendation for saturated fat (8% EI). In the study sample, 36.4% and 91.8% of the children were consuming below the AMDR for linoleic acid (LA) and alpha linolenic acid (ALA) intakes, respectively. For alpha-linolenic acid, the proportion of inadequacy was significantly higher amongst 4–8.9 year-old children, compared to older ones (17.7% vs. 8.1%). Although most of the participants were consuming within the AMDR for carbohydrates, none of the children aged 4–12.9 years were consuming above the AI for dietary fiber . Free suAs for micronutrient intakes, a low intake of vitamin D was evident in the study sample, whereby 100% of children aged 4–12.9 years were consuming below the EAR value . Low intLow intakes of zinc, magnesium, and vitamin A were significantly more prevalent in the older age group (9–12.9 years) compared to younger ones, reaching as high as 74.3% for zinc, 59.8% for magnesium and 51% for vitamin A. Similarly, the proportions of subjects having low intakes of vitamin C, folate, riboflavin, vitamin B6, and vitamin B12 were significantly higher in 9–12.9 year-old children, compared to younger ones. High sodium intake was noted among 58% of children aged 4–8.9 years and 36% of children aged 9–12.9 years, while potassium intakes exceeded AI levels in only 3.5% and 3.1% of 4–8.9 and 9–12.9 year-old children, respectively .p = 0.010) and intakes of total fat and linoleic acid below the AMDR . Nationals had also higher proportions of children not meeting the AI for vitamin K  and not meeting the EAR for magnesium .Among the total sample, nationals had a significantly higher proportion of children with intakes of free sugar above the WHO recommendation  compared to younger ones (4–8.9 years).The observed prevalence of overweight/obesity in the study sample (approximately 29%) ties well with the results on energy intake, whereby 30% of the study sample were found to exceed their estimated energy requirements (EER). The prevalence of overweight/obesity is also in line with a former study conducted on a smaller population group in the Emirate of Sharjah, where the prevalence rate was estimated at 28.2% amongst 6–11 year-old children . StudiesThe higher levels of overweight and obesity noted in our study among children aged 9–12.9 years in comparison to the younger ones (4–8.9 years) agree with the results of a recent cross-sectional study performed in governmental schools in the emirate of Ras Al-Khaimah that reported on the progressive increase of obesity with age . These oUnlike findings reported by a recent KNHS study conducted in Lebanon where 68% of children aged 4–13 years exceeded the AMDR for total fat , our resOur findings also showed that more than 70% of 4–12.9 year-old children had high intakes of free sugar. In parallel, sweets, sweetened beverages, desserts were found to be a major contributor to energy intake, providing 17% of daily calories among 4–13 year-old children in the UAE. Such foods were previously shown to be the primary sources of free and added sugars across all age categories, particularly children and adolescents ,67. SimiIn the present study, the intakes of the different food groups were compared to the dietary recommendations set by AHA/AAP. Even though more than 2/3rd of the participating children were found to adhere to the recommended number of servings of grain and grain products, all children were found to consume below the 25 g dietary fiber recommendation set by the WHO and FAO . This reOur results also showed that a high proportion of 4–12.9 -year-old children were not adhering to the recommended intakes for lean meat/beans, milk/dairy, fruits, and vegetables. Furthermore, children from the older age group (9–12.9 years) were significantly less adherent to the recommendations pertinent to lean meat/beans, milk and dairy, as well as vegetables compared to their younger counterparts (4–8-year-old children). Similar findings have been reported by a recent study conducted on the same age group in Lebanon . The lowThe assessment of micronutrient intakes in this study demonstrated a generally low adherence to DRIs, particularly for vitamin D, vitamin A, potassium, calcium, zinc, and magnesium. Previous research on children’s nutrient adequacy in the MENA region reported similar insufficient intakes of vitamin A, vitamin D, calcium and zinc, among school-aged children in KSA, UAE, and Lebanon ,93. MoreThe fact that all participating children did not meet the DRI for vitamin D is very concerning as this vitamin is essential for bone health and skeletal growth, with inadequate intakes contributing to rickets in young children and osteomalacia in adolescents . InteresAge-based discrepancy was observed in the prevalence of micronutrient inadequacies with a higher burden in the older age group, particularly for vitamin A, zinc, calcium, vitamin C and magnesium. In fact, more than half of children aged 9–12.9 years had low intakes of vitamin A. According to the WHO, the primary preventable cause of childhood blindness in the world is vitamin A deficiency . Low intMore than half of 4–8.9 year-old children and more than a third of 9–12.9 year-old children consumed above the sodium Chronic Disease Risk Reduction recommendation (1500 mg/day for 4–8.9 year-old children and 1800 mg/day for 9–12.9 year-old children) . Of concThis study has several strengths and limitations. One of its strengths is the fact that we have assessed usual nutrient intakes to assess dietary intakes and their adequacy amongst children. We have also measured the anthropometric characteristics of participating children using standardized protocols and procedures, rather than obtaining self-reported measures. For comparative purposes, we have recruited a sample of Arab non-nationals in addition to nationals, based on a ratio of 1:2. The results did not show significant differences between these 2 groups in anthropometric status but suggested that there may be differences in food consumption practices whereby nationals were found to have a higher consumption of grains compared to non-nationals. In contrast, Arab non-nationals were found to have a higher consumption of fruits and fats and oils. Differences in the intakes of free sugar and total fat were also observed between the groups, Thus, although the study sample is limited by its small size which does not allow for the generalizability of these differences, the results of the study highlight the need for more targeted research examining the diet and food consumption practices of the different population groups living in the UAE.The findings of this study ought to be considered in light of the following limitations. The first potential limitation is related to the use of the 24-HR for dietary assessment, a method that may be linked with reporting bias by caregivers . HoweverIn conclusion, this study documented a high intake of saturated fats and free sugars amongst school-aged children in the UAE, coupled with low intakes of alpha-linolenic acid and dietary fiber. In addition, the results highlight low adherence to the dietary recommendations for food groups, including fruits, vegetables, lean meat/beans, and milk/dairy products. Suboptimal intakes of key vitamins and minerals were also observed, including vitamin D, calcium, vitamin A, zinc, potassium, and magnesium, with the majority of these inadequacies being significantly higher in the older age group (9–12.9 years), compared to younger ones (4–8.9 years). Public health and nutrition education interventions are needed to promote and support healthier diets among children in the UAE, and hence contribute to optimal health in future generations.


In conclusion, our data suggest that the older a person gets, the more sharply the likelihood of developing additional diseases, such as PMS, increases. Similarly, for follow-up, the more a patient is followed up clinically over time, the higher the risk of new diagnoses increases.Second primary malignancies (SPM) are described as any primary, not synchronous, malignancy arising in a different anatomical district, with confirmed histological diagnosis. Age at diagnosis, previous non-thyroidal primary malignancy, and radioactive iodine (RAI) therapy have been proposed as independent risk factors for SPM. RAI therapy is a standard treatment for moderate-high risk differentiated thyroid cancer (DTC), and its effect on the development of SPM has become a critical topic in DTC treatment. The purpose of this retrospective single-center study was to investigate the occurrence and the possible association of non-thyroidal SPM diagnosed after DTC and RAI therapy in a cohort of 1326 consecutive DTC patients referred at our Institution for RAI treatment from 1993 to 2009. Eighty-nine patients with ages ≤ 18 years at the time of DTC diagnosis or with a follow-up of ≤12 months were excluded from the final analysis. All patients underwent a complete clinical and hematological follow-up every 6 months for a minimum of 12 months. During follow-up (mean 89 ± 73 months), 25 patients (2%) had an SPM diagnosis (mean 133 ± 73 months). The most common site of the second malignancy was the breast, accounting for 32% of all SPM, followed by colon-rectal cancer (16%), leukemia, and gynecological and kidney cancer (4%). At Cox univariable regression analysis, age at DTC diagnosis ( Differentiated thyroid cancer (DTC) is estimated to be the sixth most common cancer in 2021, with incidence rates of 10.1 per 100,000 women and 3.1 per 100,000 men and mortality rates of 0.5 per 100,000 women and 0.3 per 100,000 men ,5,6. The131I doses [Second primary malignancies (SPM), described as any primary, not synchronous, malignancy arising in a different anatomical district with confirmed histological diagnosis, is reported in patients with DTC . Actuall1I doses ,8,9,10, 1I doses ,26. HencThe purpose of this study was to investigate the occurrence and the possible association of non-thyroidal SPM diagnosed after DTC and RAI therapy in a retrospective cohort study.We performed a retrospective single-center study in a cohort of 1326 consecutive DTC patients who were referred to our Institution for RAI treatment and follow-up of DTC from 1993 to 2009. Demographic, clinical, surgical, and pathological data were noted from clinical records, including the age at the time of DTC diagnosis, the extent of surgery, the administered RAI dose, and the latest date of follow-up. According to the American Thyroid Association risk stratification [All patients underwent a complete clinical and hematological follow-up every 6 months for a minimum of 12 months (mean 89 ± 73 months). SPM was described as any primary, not synchronous, malignancy arising in a different anatomical district with a confirmed histological diagnosis. The timing of SPM occurrence with respect to DTC diagnosis was chosen to be more than 12 months after DTC. The SPM diagnosed within 12 months of RAI administration was considered synchronous and excluded from our analysis. The date of recurrence, SPM diagnosis and most recent outpatient visit were recorded as follow-up duration. If patient death occurred during follow-up, it was noted.t-test and Chi-square test as appropriate. A p-value < 0.05 was considered statistically significant. Univariable Cox regression analysis was performed for each variable. Only variables showing a p-value < 0.05 at univariable analysis were considered statistically significant. Statistical analysis was performed with Stata 15.1 software .Continuous data are expressed as mean ± standard deviation and categorical data as a percentage. Comparison between groups was performed with unpaired None of the patients potentially eligible for the study refused to participate, and all patients were able to sustain the examination. From the 1326 patients available from the analysis, 89 subjects with age ≤ 18 years at the time of DTC diagnosis or with a follow-up ≤12 months were excluded from the final analysis leaving 1237 patients  for the final analysis .Baseline characteristics of the patient population, histological characteristics, follow-up duration and dose administration, are summarized in The mean initial RAI dose is 3552 ± 1110 MBq The mean number of treatments is 1.44 ± 1.067, and the average treatment interval is 25 ± 2 months.p < 0.0001), while no differences in gender and in histological type were found (131I activity (6364 ± 5176 MBq vs. 5710 ± 5820 MBq). Interestingly, follow-up duration was significantly longer in patients experiencing SPM compared to those without documented SPM .As shown in re found . Moreove131I activity administered. The most common site of the SPM was the breast, accounting for 32% of all SPM, followed by colon-rectal cancer (16%), leukemia, and gynecological and kidney cancer (4%). To note, only one out of the eight female patients developing breast cancer was of childbearing age, while the other seven were in postmenopausal age at the time of RAI, further supporting data that excludes a potential relationship between RAI and breast cancer development.SPM histology and number are described in p < 0.001) and follow-up duration (p < 0.005) were the only factors significantly associated with SPM onset.At Cox univariable regression analysis, as described in Of note, only 11 out of 25 patients showed SPM. By mean, 44% of the subjects with the event had the secondary malignancy diagnosis within five years of RAI therapy.At the end of the follow-up, 25 patients had died. Among these, 2 patients died due to SPM, and 23 patients died due to non-oncological reasons. There were 20 patients who died from cardiovascular events and 3 patients who died from infection accidents.https://www.registri-tumori.it/cms (accessed on 1 September 2022), it has been reported that the number of observed second cancers in patients with DTC in the Italian population is 404/12,866 patients overall, with a frequency of 3% of patients showing an SPM after DTC. Our findings are thus in line with Italian data. Age at DTC diagnosis and duration of follow-up were the only significant factors associated with the development of SPM after RAI. This finding is not surprising given the excellent long-life expectancy of the investigated population. It becomes clear that a longer follow-up certainly has a better chance of bringing out new diagnoses such as SPMs, especially in patients on surveillance programs, as in the case of patients with DTC [In the present study, a relatively low percentage of patients (2%) showed SPM during follow-up. According to data available from the Italian Tumor Registry Association (AIRTUM) on with DTC ,15.Discordant data regarding the development of SPM in patients treated with RAI have been reported ,19,20,27131I is not significantly associated with the development of an SPM, only the duration of follow-up shows a significant relationship with the risk of an SPM after DTC supporting the idea that a long follow-up determines more effective health surveillance including SPM diagnosis. Likewise, Mei et al. [Our findings are consistent with those from Cappagli et al. , who reti et al.  found thi et al. .Furthermore, a recent meta-analysis evaluated the risk of breast cancer in patients with DTC receiving RAI taking into consideration 14 studies  and repoCrocetti et al. , found t131I administered.On the other hand, Brown et al.  evaluateThus, on the one hand, our data demonstrate a low number of SPM. On the other, larger cohort studies have reported higher rates of SPM. However, given the observational retrospective nature of the present analysis, some events would have been missed on follow-up, explaining a slight underestimation of SMPs in our investigation. Indeed, within DTC follow-up, the enrolled patients were not routinely referred to clinical and imaging tests that were not directly related to DTC surveillance.Hong et al. , in a muThe incidence of SPM in the present study is very low compared to that found in some studies described in the literature ,14,15,19For some authors ,13,15, t131I cumulative activity dose. The present investigation demonstrates that 131I cumulative activity dose is not associated with SPM development in DTC patients after RAI therapy, even considering different administered activity categories. This finding is in agreement with numerous prior studies [131I administered. Therefore, the association between RAI and the risk of SPM development in DTC patients is still controversial. It is certainly very important that every patient must be contextualized and deserves a personal medical evaluation based on their genetic and clinical background [Another factor worth considering is the  studies ,28,29,30 studies  total cu studies  and Rubickground ,18,19,20ckground  demonstrThe results of our study suggest that the older a person gets, the more sharply the likelihood of developing additional diseases, such as SPM, increases.In this context, it should be considered that the pediatric population has been excluded from the final analysis in light of known differences between adult and pediatric DTC regarding clinical, molecular, and pathological characteristics . Thus, sSimilarly, for follow-up, the more a patient is followed up clinically over time, the higher the risk of new diagnoses increases.131I cumulative activity was not associated with SPM development. Breast cancer was the most common secondary non-thyroid cancer. Our data can also be read in light of the long-life expectancy of patients with DTC, making the malignancy rate of this patient category like general population findings. The high incidence of breast cancer in our cohort of patients can be explained by the high prevalence  of women enrolled.In the present study, only increasing age at the DTC diagnosis and follow-up length were significantly associated with SPM onset. On the contrary,


Although research generally showed that holding materialistic beliefs would lead to poor developmental outcomes, few studies have used adolescent delinquency as an outcome measure. In addition, the intervening processes between materialism and adolescent developmental outcomes are unclear. In particular, it is not clear how materialistic beliefs influence egocentrism and adolescent delinquency. Methodologically, the existing studies have several weaknesses, including small samples, cross-sectional research designs, and being limited to people living in Western cultures. Using two waves of data collected from Sichuan, China (N = 4981), we studied the predictive effect of adolescent materialism on delinquency and the mediating role of egocentrism. Over two occasions separated by six months, students aged 11 and above responded to a questionnaire evaluating adolescent materialism, egocentrism, and delinquency . Results of multiple regression analyses suggested that materialism at Time 1 positively predicted Time 2 egocentrism. Additionally, Time 1 materialism positively predicted the level and change in Time 2 delinquency. Finally, based on 5000 bootstrap samples with gender, age, ethnic group, and Time 1 delinquent behavior as covariates, PROCESS analyses showed that egocentrism partially mediated the influence of Time 1 materialism delinquency and its change at Time 2. This study suggests that materialistic beliefs shape egocentrism, which further strengthens adolescent delinquent behavior. This study also replicates the findings of a pioneer study in China reported previously. For adolescents, the desire to possess trendy commodities may contribute to delinquent behavior such as stealing. In a report on knife crime in London, Lais  used theWhile common sense suggests that material possession and material consumption lead to happiness, research findings do not provide strong support for this belief. Dittmar, Bond, Hurst and Kasser  reviewedIn another review, Kasser  pointed In a pioneer study on the relationships between materialism and egocentrism and adolescent delinquency in the Chinese context, Shek et al.  reportedConceptually, there are several issues surrounding the linkage between materialism and well-being. The first issue is the conceptualization of well-being and the related measures. In the literature, while researchers have used different measures of well-being, such as subjective well-being , self-evaluation , mental disorders , and health risks, antisocial behavior has seldom been used as a developmental outcome indicator, particularly in adolescents. Moreno et al.  conceiveStudies have shown that materialism is strongly related to impulsive behavior  that comRegarding the linkage between values and delinquency, Bilsky and Hermann  remarkedThe second conceptual issue concerns the relationship between materialism and different dimensions of “self”. Primarily, there are views suggesting that self-related constructs such as negative self-appraisal and low self-esteem are causes or concomitants of materialism ,24. In cIn the model proposed by Donnelly, Ksendzova, Howell, Vohs and Baumeister , it is sTheoretically, as very few studies have explored the mediating mechanism of the association between materialism and personal well-being, we do not know much about the mediators involved. As pointed out by Górnik-Durose, while numerous studies have revealed the negative influence of materialism on individual well-being, “mechanisms underlying this association still remain partially unexplained”  p. 305)530,31]. Shek, Li, Zhu and Shek  also poiSecond, regarding the assessment of materialism, Kasser  explicitFinally, most of the studies in the field are Western studies. Shek, Li, Zhu and Shek  argued tRegarding Confucianism, Low  comparedWith reference to the conceptual and methodological limitations in this field, we attempted to conduct two waves of longitudinal data to investigate the relationships between materialism, egocentrism, and delinquency, with egocentrism proposed as the mediating factor. Specifically, we asked four research questions as follows:Research Question 1: What are the relationships between adolescent materialism and delinquency concurrently and longitudinally? According to previous findings , we hypoResearch Question 2: Is adolescent materialism related to egocentrism at a single time point and over time? Based on the preceding discussion, we proposed that materialism would positively predict egocentrism at each wave and over time (Hypotheses 2a and 2b);Research Question 3: What are the concurrent and longitudinal relationships between egocentrism and adolescent delinquency? According to past findings , we expeResearch Question 4: Does egocentrism mediate the relationship between materialism on delinquency? Based on the findings of Shek, Li, Zhu and Shek , we hypoTo overcome the limitation of the predominance of cross-sectional studies, we employed a short-term longitudinal design with a collection of data with a six-month interval between the two waves of data in five schools in Chengdu. There were 623 and 317 public primary and junior secondary schools, respectively, and 156 schools admitting both primary and junior secondary students in Chengdu in 2020 . Among tBefore data collection, we obtained ethical approval from Sichuan University and consent from the school, parents, and students. Wave 1 data were collected from December 2019 to January 2020 before the COVID-19 outbreak in Wuhan, China, and the school lockdown. Wave 2 data were collected between June 2020 and July 2020 after the resumption of schools because of the gradual stabilization of the pandemic in China. During the data collection, two well-trained research assistants were present in the classrooms. As we focused on adolescents in this paper, we utilized data collected from adolescents aged 11 years or above . There were 4981 students who completed the questionnaire at both waves  with 2566 male students (51.5%) and 2415 female students (48.5%). A total of 143 students refused to participate in the study.During the data collection process, the research assistants and schoolteachers helped go through the questionnaires quickly to ensure students responded to all questions without looking at the students’ responses. Then the research assistants collected the completed questionnaires without the involvement of the teachers. All the data were kept confidential by the research team without revealing any personal information in the research outputs.Shek et al.  developeBased on the data collected from 1658 adolescents, Shek, Yu and Siu  developeTo assess delinquency, we employed a validated 12-item scale that covers delinquent behaviors in the previous year ,39. SomeThe respondents were also invited to give information on their socio-demographic background  through self-report. Compared to Shek, Li, Zhu and Shek , there wAs students’ data were nested within groups (class and schools), we examined the intra-class correlations for the variables under investigation. Results showed that the mean intra-class correlation was 0.045. Based on the recommendation of Guo , there if2, which is an informative and standardized measure to evaluate effect size for multiple regressions [f2 larger than 0.02, 0.15, and 0.35 represent small, medium, and large effect sizes, respectively. Finally, PROCESS analyses were performed to assess the mediating effect of egocentrism on the prediction of materialism at Wave 1 on delinquency and its change at Wave 2 [A series of hierarchical multiple regression analyses was conducted to answer the research questions. This approach has commonly been used in the field ,46. At eressions . Accordiressions  recomment Wave 2 .r = 0.238 and 0.103, respectively, p < 0.001). Regarding the change in materialism, egocentrism, and delinquency over the two waves, results of paired t-tests (N = 4981) showed that Wave 1 materialism  and egocentrism  were lower than Wave 2 materialism  and egocentrism , respectively. However, Wave 1 delinquency  was higher than Wave 2 delinquency .β = 0.34, p < 0.001, Cohen’s 2f = 0.120 and β = 0.18, p < 0.001, Cohen’s 2f = 0.034, respectively) and Wave 2 .For the concurrent predictors of adolescent delinquency , after cβ = 0.22, p < 0.001, Cohen’s 2f = 0.048 and β = 0.09, p < 0.001, Cohen’s 2f = 0.008, respectively). We also examined the influence of Wave 1 materialism and egocentrism on the change in delinquency at Wave 2 by controlling delinquency scores. β = 0.08, p < 0.001, Cohen’s 2f = 0.006). While the predictive effect of egocentrism at Wave 1 on change in delinquency at Wave 2 was not found , egocentrism at Wave 2 predicted the change in Wave 2 delinquency  after controlling the covariates.For predictions over time see , materiaβ = 0.20, p < 0.001, Cohen’s 2f = 0.040) and its change over time  after controlling the covariates.Results revealed that materialism significantly predicted egocentrism at Wave 1 and Wave 2. Additionally, Wave 1 materialism predicted Wave 2 egocentrism . The findings showed that Wave 2 egocentrism partially mediated the relationship despite the small effect size.The present study responded to the conceptual and methodological limitations of the existing studies on the relationships between materialism and well-being ,6, and tThere are also two advances in this study. First, as adolescent delinquency has seldom been used as a measure of well-being in the existing studies , this stRegarding Research Question 1, multiple regression results showed that materialism was a significant concurrent and longitudinal predictor of adolescent delinquency as well as its change over time. While acknowledging the small effect size of the significant effect, the present finding expands the literature on the predictive relationship between materialism and adolescent delinquency . In partConcerning Research Question 2, Wave 1 materialism predicted egocentrism at both waves as well as change in egocentrism over time. These findings underscore the close linkage between materialism and egocentrism and suggest that materialistic beliefs may lead to exaggeration of the importance of oneself and focus on oneself. The link between materialism and egocentrism can be understood in terms of the self-focused attributes of materialism—focusing on what one possesses and what one lacks (envious of the possessions of others) as well as not being willing to share one’s possessions with others. As there are few studies in this area, further studies should be conducted to examine how materialism is related to different dimensions of egocentrism. At the macro level, it would be interesting to explore the relationship between materialism  and egocentrism at the national level.Concerning Research Question 3 on the predictive effect of egocentrism on delinquency, the present findings are consistent with the previous findings that adolescent delinquency was related to egocentrism and lack of empathy . AlthougNevertheless, alternative interpretations may explain the associations between adolescent materialism and delinquency observed in the present study. For example, there may be other variables, such as low socioeconomic status, dysfunctional values and beliefs, and undetected mental health problems, that underly both materialism and delinquency among adolescents. Additionally, adolescent misconduct may reinforce their unhealthy orientation. For example, externalizing behavior predicted adolescents’ morality in one year . Thus, iRegarding how to prevent adolescent delinquency, the present findings suggest that it is helpful to minimize materialistic beliefs and egocentrism. One possibility is to strengthen the developmental assets in adolescents, such as promoting their spirituality  and social awareness , and building up positive and healthy self-identity  through positive youth development (PYD) programs ,55,56. BAnother contribution of the study is that we replicated the findings of Shek, Li, Zhu and Shek . BasicalThe crisis of replication has been highlighted in the literature. Freese and Peterson remarked, “science is presently in the throes of a crisis of replication”  (p. 148)Of course, it is understandable that the delinquent behavior of the students may be affected during COVID-19. For example, because of the restriction of social interaction and having online schooling, the chance of engaging in some delinquent behavior  would reduce. In the present study, we actually found that delinquent behavior decreased across time. With reference to the reflections highlighted in Shek , there iAlthough this study replicates the findings of Shek, Li, Zhu and Shek , we shouFourth, although there is support for the reliability and validity of the measures of materialism and egocentrism , there is a need to collect further data on the concurrent validity and social desirability of the measures. In addition, we used self-report delinquent behavior in the present study. In future, it would be helpful to include official statistics on adolescent crimes so that we can have a more holistic picture of this problem area. However, as some adolescent delinquent behavior may not be captured by the criminal justice system , official statistics also have limitations. Furthermore, many researchers are still relying on self-report measures of delinquency in their studies of adolescent delinquency ,66. As aFifth, besides the issue of self-report delinquency, as we asked the participants to report their delinquent behavior in the past year and the interval between the two waves was around six months, there may be an overlap in the delinquency measures at these two waves. However, as we also assessed the predictive effect of Wave 1 materialism on the change in Wave 2 delinquency, this problem may be partially minimized.r = −0.15) for the relationship between materialism and personal well-being . As Dittmar et al. suggested, the use of multifaceted measures of materialist values can help clarify the effects of different aspects of materialism orientations on personal well-being.Sixth, it is noteworthy that the magnitude of the effect size surrounding the significant findings is small. Hence, we should be aware of the differences between statistical and practical significance. Although statistical significance demonstrated significant effects, these effects may not be large for practical outcomes, which should be interpreted with caution. However, we should note several points. First, the magnitude of effect sizes is usually not very high in social science research, particularly in longitudinal studies ,69. SecoNevertheless, the present findings replicated the findings reported in Shek et al.  and provBy replicating the findings of Shek, Li, Zhu and Shek , this st


Drug-induced liver injury (DILI) is uncommon but potentially lethal. Over 6 years, 2533 children with acute liver disease were identified in our center, 48 of which suffered from toxic hepatitis, and 40 exhibited DILI . The most affected children were in the 13–17-year-old age group. The mean time between drug ingestion and disease diagnosis was 25.4 h for paracetamol-related DILI and 21.6 days for the albendazole-related group. Clinical features were mostly gastrointestinal, jaundice being reported in 30% of the cases. Regarding the type of liver injury, for 70% of the patients it was hepatocellular (mostly paracetamol toxicity), for 11% cholestatic, and for 19% mixed . The mean initial ALT value was 1020 U/L for all DILIs. Coagulopathy was only identified for the acetaminophen-related group. The median number of hospitalization days was 6.9 for DILI related to acetaminophen ingestion, compared with 7 for the idiosyncratic pattern. When applying the DILI severity index, 81% of the patients were categorized as having a mild hepatic ailment, while 19% had a moderate–severe or severe disease. No deaths were reported in the study group. The diagnosis of DILI involves the exclusion of other causes of liver injury; therefore, it is considered one of the most challenging diagnoses in hepatology. Drug-induced liver injury (DILI) is one of the most challenging liver disorders faced by pediatric hepatologists . DILI isDILI consists of altered liver function as a consequence of exposure to hepatotoxic substances or their metabolites. In 2011, an international expert working group meeting proposed a new definition for DILI based on the following criteria: (1) alanine aminotransferase (ALT) elevation ≥5 upper limit of normal (ULN); (2) alkaline phosphatase (ALP) elevation ≥2 ULN in the absence of known bone pathology leading to increases in the ALP level  concentrations); or 3) ALT ≥3 ULN and simultaneous elevation of total bilirubin concentrations above 2 ULN  ALT ≥3 U.Pharmacologically, there are two types of DILI: dose-dependent or intrinsic and dose-independent or idiosyncratic. Dose-dependent DILI (such as that due to acetaminophen overdose) appears when the drug dose exceeds its known limit for toxicity; it is predictable and reproducible, there is a short period of latency between exposure and DILI manifestations, and liver damage is proportional to the administered dose. Idiosyncratic DILI  is unpredictable, the period of latency is variable, and liver damage is not dose-dependent, frequently developing at therapeutic doses ,2.Acetaminophen is one of the most commonly used drugs in pediatrics, due to its analgesic, antipyretic, and anti-inflammatory effects. When used in therapeutic doses, paracetamol has few side effects. It is metabolized by phase II conjugating enzymes, mainly UDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT), converting the drug to nontoxic compounds, which are subsequently excreted in the urine. Approximately 5–9% of the drug’s metabolism is achieved through cytochrome P450 enzymes (CYP), especially CYP 2E1, resulting in a highly reactive intermediate metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is detoxified by conjugation with glutathione (GSH). Only 2% of acetaminophen is excreted unchanged in the urine .Albendazole is a benzimidazole derivative with a wide anthelmintic spectrum, acting through the metabolite albendazole sulfoxide, synthetized after the first hepatic pass. Albendazole sulfoxide is mainly bound to plasma proteins up to 70%) and is distributed throughout various tissues. The excretion of albendazole sulfoxide is probably most common through the biliary system [0% and isThere is limited information about the immune responses induced by drugs, including drugs which are metabolically activated, but cluster of differentiation (CD) 86 and CD54 expression levels on monocytic cells were notably upregulated by treatment with albendazole in the presence of CYP3A4 [Patterns of liver injury—hepatocellular, cholestatic, or mixed—have been defined biochemically by the ALT and ALP levels when compared with the reference levels and/or the R ratios between actual ALT/ALT(ULN) and actual ALP/ALP (ULN) at presentation .The widely used scores for causality assessment of DILI, the Roussel Uclaf Causality Assessment Method (RUCAM) score and the Maria and Vittorino score, are used as suggestive scores for idiosyncratic DILI ,10. The DILI is mostly identified based on a diagnosis of exclusion; therefore, detailed history and anamnestic data, such as the time of exposure, period of latency, and effect of a subsequent exposure, must be carefully assessed. In the absence of diagnostic tests and/or biomarkers, the diagnosis of DILI requires a high index of suspicion after diligently excluding other causes of abnormal liver tests .In this paper, we report a cohort of 40 children with DILI, enrolled in a single pediatric tertiary center. The research focused on the most common hepatotoxic agents , the epidemiological and clinical presentation and laboratory findings of the patients, and severity scores of the cohort studied. The rationale behind writing this report was the ease in prescribing this medication by physicians and the high accessibility of some toxic medications to children, but also the low level of physician awareness of the importance of reporting DILI cases. The aim of this study was to present an update on the diagnostic approach to each type of DILI, DILI natural history, and the current management strategy, based on clinical and biochemical findings, to improve the diagnostic accuracy and achieve a faster diagnosis of DILI.We conducted a retrospective and prospective observational study that included pediatric patients aged 1 to 17 years with acute liver disease, admitted to the Pediatrics Department of “Grigore Alexandrescu” Emergency Children’s Hospital in Bucharest over a period of 6 years. We collected data on the patients’ age, possible causes of liver injury, type of substance administrated and its potential role on DILI, associated symptoms, laboratory assessments, outcomes, etc.After informed consent was obtained, an extensive medical history was recorded, including recent alcohol or medication consumption, smoking history, drug intolerances, and symptoms in the 3 months leading to DILI onset. A complete physical examination was performed, and detailed information regarding all relevant laboratory and imaging studies was reviewed to ensure that the patients met the enrolment criteria. For all patients, the abnormal liver tests were repeated within 24 h for confirmation.Using the eligibility criteria for acute liver disease, we enrolled patients with ALT elevation ≥5 ULN or ALP elevation ≥2 ULN in the absence of a known bone disorder justifying the increase in ALP level (with elevations in GGT concentrations), or ALT ≥3 ULN and simultaneous elevation of total bilirubin concentration >2 ULN, or an INR above 1.5 in the absence of another cause of hyperbilirubinemia or hypoprothrombinemia.-Screening tests for hepatitis A, B, C, D, E, Epstein–Barr virus, herpes virus, adenovirus, cytomegalovirus, parvovirus B19, and SARS-CoV-2 (if appropriate);-Assessment of the erythrocyte sedimentation rate, albumin levels, gamma globulins, immunoglobulin G, antinuclear antibodies (ANA), smooth muscle antibodies (SMA), and liver–kidney microsome antibodies (LKM1);-Alpha 1 antitrypsin serum level;-Serum ceruloplasmin level, 24 hour urine copper;-Sweat test;-Immunoglobulin A and immunoglobulin G tissue transglutaminase antibodies;-Thyroid hormones levels-Total lipids, triglycerides, and cholesterol levels and coagulation profile;-Abdominal ultrasound.The patients were labelled as DILI patients after excluding infectious diseases, autoimmune liver disease, metabolic disorders, diseases of the biliary tract, and non-alcoholic steatohepatitis. The laboratory tests also aimed to assess the severity of liver involvement. The following investigations and assays were performed:Data analysis led to defining the type of liver lesion and the pharmacological mechanism and to determining the scores for severity and causality. Microsoft Excel 2010 was used for organizing and analyzing the data.We identified 2533 children aged 1 to 17 years with suspected acute liver injury. Out of a total of 2533 hospitalized children for hepatic disease, 48 (1.89%) patients were found to have toxic hepatitis; among them, only 40 patients were diagnosed with DILI according to the definition. A total of 22 patients with paracetamol-related DILI and 14 children with albendazole-related DILI were admitted to our center during the analyzed period of time . There were only three other classes of medication involved in DILI in our cohort—metformin (one patient), opioids (one patient), and antimicrobials . Other common substances involved in hepatotoxicity were insecticides, heavy metals, and mushrooms .The mean dose for acetaminophen was 128 mg/kg (ranging between 98 and 221 mg/kg). Albendazole was administrated without medical recommendation to eight patients, and for suspected giardiasis or oxyuriasis in the other cases.From the entire cohort of DILI, the most affected children were in the 13 to 17 years age group (52.5%), with a peak incidence in adolescents aged 15–16 years (27.5%). The incidence curves based on age for DILI secondary to acetaminophen and albendazole are presented in For the paracetamol overdose DILI group (intrinsic DILI), the time between the ingestion and the identification of liver cytolysis, at the time of medical evaluation, ranged from 6 to 49 h (mean 25.4 h), whereas for the albendazole group (idiosyncratic DILI), the time from ingestion to symptom onset or the identification of liver injury ranged between 3 and 89 days (mean 21.6 days).Among the symptomatic children, the most common clinical features were abdominal pain (50%), followed by nausea and vomiting (45%); in most cases, these symptoms were reported in the acetaminophen-related DILI group. Jaundice was only observed in 30% of cases, of which nine were in the albendazole-related DILI group, and only three were in the acetaminophen overdose DILI group. Four patients complained of a headache, and three others reported fever, symptoms suggestive of an associated acute illness. No patients were identified to have renal or neurologic complications in our cohort. None of the children had a known history of pre-existing liver disease. Six children (15%) were asymptomatic, the diagnosis of DILI being established after incidentally identifying liver cytolysis and excluding other liver diseases.In our cohort, according to the R ratio, we noticed hepatocellular injury in 70% of cases, cholestatic injury in 11%, and mixed injury in 19% .The types of liver injury, determined based on the R ratio for the paracetamol and the albendazole groups, were different: we observed that, for intrinsic DILI (secondary to paracetamol overdose), the hepatocellular pattern was predominant (84% of cases), whereas for idiosyncratic DILI , the cholestatic pattern and mixed injury were more common, at 17% and 28%, respectively.The mean initial ALT value was 1020 U/L for all DILI cases (ranging between 18 and 8036 UI/L). The mean value of transaminases for acetaminophen-induced DILI patients was 1334 UI/L, whereas for the albendazole-induced DILI group, it was 714 UI/L.The mean initial total bilirubin level in the DILI acetaminophen-related patient group was 1.28 mg/dL (ranging between 0.3 and 4.2 mg/dL), whereas for the conjugated bilirubin value, it was 0.38 mg/dL (ranging between 1.17 and 0.1 mg/dL). For the idiosyncratic DILI patient group, the total bilirubin mean value was 2.68 mg/dL (ranging between 0.43 and 17 mg/dL), and the conjugated bilirubin mean value was 1.81 mg/dL (ranging between 0.28 and 13.4 mg/dL).The intensity of cholestatic syndrome should be indicated by ALP, whose mean value was normal; however, even if GGT is not a constant marker of cholestasis, its value was elevated, with a mean of 44.3 UI/L (ranging between 12 and 232 UI/L) for intrinsic DILI secondary to paracetamol overdose, compared with 80.2 UI/L (ranging between 11 and 239 UI/L) for idiosyncratic DILI. The idiosyncratic DILI pattern is mainly characterized by cholestatic syndrome with less intense cytolysis, whereas the intrinsic pattern presents more severe cytolysis with less intense cholestasis.Coagulopathy, defined by an INR > 1.5, was identified in 12 cases (30%), whereas prothrombin activity was <80% for 16 patients (40%), all belonging to the acetaminophen-related DILI group.The median number of hospitalization days was 6.9 (ranging between 1 and 54) for DILI related to acetaminophen ingestion, compared with 7 (ranging between 1 and 19 days) for idiosyncratic-pattern DILI.When applying the DILI severity index  , it is hWhen applying the RUCAM score for the albendazole-related group in our research, its values confirm the high likelihood of liver disorder associated with medicine ingestion, the score ranging from 10 to 13 points for all patients. In one patient, re-exposure occurred.The demographics, clinical parameters, and outcomes of the three DILI groups  are presented in According to the American College of Gastroenterology guidelines, hepatocellular liver injuries secondary to viral hepatitis , autoimmune hepatitis, vascular liver disease (Budd–Chiari syndrome and ischemic liver injury), and Wilson’s disease need to be excluded when considering DILI. For the cholestatic pattern, biliary obstruction and biliary autoimmune diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), were excluded. Other diagnoses that should be excluded are hemochromatosis, alfa1-antitrypsin deficiency, non-alcoholic fatty liver disease (NAFLD), and non-alcoholic steatohepatitis (NASH) .Acute hepatotoxicity in children may be the result of an intentional or unintentional overdose. The latter could be the consequence of accidental ingestion, frequent administration, the use of associated hepatotoxic drugs, or the use of multiple acetaminophen-containing products ,15.More than one-half of our patients were admitted due to acetaminophen-induced liver injuries, which is in line with data from the United States, where acetaminophen is reported to be the most common drug involved in DILI-associated acute liver failure. Acetaminophen is a standard choice for contemporary pain management and antipyretic treatment in a variety of patients, including children. Some studies reported acetaminophen to be safe for use in preterms. The pediatric posology is 10 to 15 mg/kg/dose every 4 to 6 h, not exceeding five doses in 24 h, the maximum daily dose being 75 mg/kg/day. Usually, these doses are considered risk-free, but hepatotoxicity has been reported even with doses under the recommended limits. Toxicity is likely to occur at doses >150 mg/kg . In our The mechanism of injury is dose-related. Even if children are less susceptible to complications, due to the treatment with N-acetylcysteine, there are many cases of acute hepatic failure attributed to acetaminophen ,16. SelfIn our research, in both the albendazole- and the paracetamol-related DILI groups, most children were adolescents, with a mean age of 7.42 and a median age of 12.91 years old. For the acetaminophen-related DILI group, most patients were aged over 12 years, and the medication was ingested voluntarily, in the absence of any medical recommendation. Almost all children in the albendazole cohort were aged under 12 years; the medication was administered according to dosage, but not always based on medical recommendations. Our study demonstrated an increased incidence among adolescent girls in the group of patients with DILI acetaminophen overdose, the ingestion being intentional, for suicidal purpose; only for one patient was the ingestion unintentional , raising the issue of possibly negligent parental care.The onset of acute intoxication with acetaminophen is rapid. Usually, it starts with the marked elevation of ALT and aspartate aminotransferase (AST) serum levels in 24 to 72 h after ingestion, followed by clinical symptoms in the following 48 to 96 h. The first stage is also called asymptomatic or with minimal clinical changes. Right upper quadrant pain, elevation in liver enzymes, alteration of coagulation parameters, and in severe cases, evidence of nephrotoxicity or pancreatitis, may appear after 24 h. Evidence of liver failure and multi-organ failure is common 72 h after ingestion, and in this stage, death might also occur. When attained, recovery is seen in 4 to 14 days .In our research, among the symptomatic children, the most common clinical features were abdominal pain (50%), followed by nausea and vomiting (45%); in most cases, these symptoms were reported in the acetaminophen-related DILI group. Liver injury secondary to acetaminophen toxicity was indicated by high levels of liver enzymes (above 10 ULN), with no cholestasis but with coagulopathy in 36% of children.DILIN research which included 30 children with idiosyncratic DILI demonstrated that more than one-half of the cases were caused by antimicrobial medication and tuberculostatic agents, followed by anticonvulsant drugs, with albendazole-related liver disease not being mentioned . Our resIt is known that in cases of albendazole administration, the elevation of liver enzymes is often observed, with return to normal values after drug discontinuation, without any further complications. Few cases of obstructive jaundice have been reported . Rare caHepatocellular DILI is characterized by ALT ≥ 5 times greater than the ULN for an ALT/ALP ratio ≥5 times greater than the ULN. Cholestatic DILI is defined by ALP ≥2 times greater than the ULN or an ALT/ALP ratio ≤2 times greater than the ULN; mixed DILI is diagnosed when the ALT/ALP ratio is <5 but >2 times greater than the ULN ,6.In our cohort, according to the R ratio, we noticed hepatocellular injury in 70% of the cases, cholestatic injury in 11%, and mixed injury in 19%. We found previous research reporting that hepatocellular injury patterns are more common in younger patients, whereas cholestasis prevails in older patients . These fScores that use more parameters are more appropriate for appreciating the actual disease severity compared to scores obtained using the ALT value alone.The RUCAM score is a structured, standardized, and validated tool for assessing hepatotoxicity. It is mainly used for idiosyncratic reactions. Key items for RUCAM include clinical, biochemical, and serologic features ,24. WhenWhen applying the DILI severity index , 81% of the patients 29 patients) were categorized as having a mild hepatic impairment, whereas 19% (7 patients) were classified as having a moderate–severe or severe disease. No deaths were reported in the study group  patients.In order to diagnose DILI, the exclusion of other diagnoses is of utmost importance; therefore, providing accurate medical information to the patient and family is imperative, helping them better understand their condition, treatment options, and risks . Limitations of our study include the retrospective design, lack of the date of disease onset , and no long-term follow-up of the patients.The diagnosis of DILI involves excluding other causes of liver injury, so it is considered to be one of the most challenging diagnoses in hepatology. Here, the conditions of many patients diagnosed with toxic liver disease were secondary to paracetamol and albendazole use. DILI was most frequent among adolescent girls. Abdominal pain was one of the most significant clinical features. For intrinsic DILI, the predominant pattern was hepatocellular injury, whereas for idiosyncratic DILI, cholestatic syndrome was predominant. Our study contributes to the understanding of drug-induced liver injury, even if our data may not be applied to all DILI patients.


Sleep occupies one third of a person’s life, and good sleep quality is an important factor to ensure good health.This study investigated and analyzed the occupational stress, mental health and sleep quality of oil workers, analyzed the effects of occupational stress and mental health on sleep, and explored the effects of the interaction between occupational stress, mental health and cytokines on sleep.In this study, stratified cluster random sampling was used to conduct a cross-sectional survey on the occupational stress, mental health and sleep quality of 1,141 oil workers in the Occupational Health Examination Department of Karamay Central Hospital, from June 2019 to January 2020, and 30% of the participants were randomly selected for measurement of their cytokine levels: interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor α (TNF-α). The objectives were to analyze the effects of occupational stress and mental health on sleep quality, and to explore the effects of occupational stress, mental disorders and cytokine interactions on sleep.P < 0.05). The scores for occupational stress, mental health, and sleep quality were positively correlated (P < 0.05). Multivariate logistic regression analysis showed that age (30–45 years) , junior college and above , borehole operation , extraction of oil , drilling , shift work , occupational stress , and mental disorders  are risk factors for sleep disorders. In the high occupational stress group and the mental disorders group as the control group, the results showed that the interaction between IL-2 and moderate occupational stress , IL-2 and non-mental disorders  were protective factors for the occurrence of sleep disorders. The results of structural equation modeling analysis showed that occupational stress and mental health had positive predictive effects on IL-2 level and sleep quality . Occupational stress had a direct positive predictive effect on mental disorder (β = 0.25), and sleep disorder had a direct negative predictive effect on IL-2 concentration (β = −0.21).There were 646 individuals (56.6%) who suffered from sleep disorders; the incidence of sleep disorders differed according to sex, age, professional title, working years, type of work and shift (Oil workers have serious sleep problems, so effective measures should be taken to reduce occupational stress and relieve mental health problems, and cytokine levels can be used as a predictor of sleep disorders. Sleep is indispensable to human life activities: it is an essential factor in the maintenance of energy, and the maintenance and promotion of health. Good sleep not only protects cerebral cortical cells and replenishes their energy, but also regulates the balance of excitatory and inhibitory activities of the body, reduces fatigue, improves cognition and acceptance, improves mental health, and helps tissues and organs to work efficiently .The term sleep disorders usually refers to acute or chronic prolonged sleep latency, excessive awakening in the sleep period, shortened sleep time, reduced sleep efficiency or poor subjective/objective evaluation of sleep quality . Sleep dOccupational stress refers to harmful physical and psychological reactions that occur when job requirements do not match workers’ abilities, coping resources and demands . In receCell factors are an important part of the immune system, acting between the neuroendocrine system and the immune system, and allowing them to communicate with each other. The interaction medium is made up of immune cells and some non-immune cells that stimulate the synthesis and secretion of small proteins with a broad range of biological activities in the immune response, whose effects and adjustment play important roles in maintaining health and homeostasis. Interleukins (IL) are a class of cytokines produced by and used by a variety of cells, which include interleukin 2 (IL-2), interleukin 6 (IL-6), and interleukin 8 (IL-8). Their functions involve the expression and regulation of the immune response, acting on cells such as lymphocytes and macrophages. Studies have shown that sleep disorders such as sleep apnea, insomnia and REM sleep behavior disorder are associated with elevated levels of inflammatory molecules , 17. GivOil workers in Xinjiang generally work in the Remote Gobi Desert with a harsh natural environment. The long-term lack of family companionship and high-pressure working environment means that workers are prone to occupational stress and other mental health problems. In addition, the nature of shift work makes sleep problems more frequent. There are many reports on occupational stress and the mental health of oil workers, but there are few studies on the effects of occupational stress, mental health problems and cytokine interaction on sleep. Therefore, this study investigated and analyzed occupational stress, mental health, sleep quality and the level of cellular factors in Xinjiang oil workers, and explored the effect on sleep of their interactions.From June 2019 to January 2020, a stratified cluster random sampling method was adopted to select petroleum company workers who underwent physical examination in the Occupational Health Examination Department of Karamay Central Hospital of Xinjiang as the participants in this survey. After communicating with the management of the occupational disease physical examination department of the hospital before the survey, the list of employees of the company requiring physical examination was obtained. After the physical examination personnel were numbered, the study participants were randomly selected using the random number table method. Two large, medium and small oil companies  were selected, and 200 people were randomly selected from each company. Questionnaires were distributed to randomly selected participants on the day of their physical examination and returned after they were filled in. Inclusion criteria were:(1) employees aged 18–60 years with ≥1 year of service; (2) individuals who had not taken psychotropic drugs or sleeping drugs in the past year; (3) those who participated voluntarily in this survey. Exclusion criteria: (1) individuals who had retired; (2) those who have taken psychotropic drugs or sleep drugs in the past year; (3) those who refuse to participate in the survey. A total of 1,200 questionnaires were sent out in this survey, and 1,141 valid questionnaires were finally collected, with an effective questionnaire recovery rate of 95%.In this study, a total of 646 people, accounting for 56.6% of the total, were screened for positive sleep disorders; 30% of the questionnaire respondents were randomly selected as the experimental research participants, giving 342 individuals. Therefore, 171 people were selected from the sleep disorder group and the control group, respectively, in this study, and 1:1 matching was adopted between those who were positive for sleep disorder and those who were negative for sleep disorder at age ±1 years old and of the same sex; the latter were selected as controls for a case–control study.The Occupational Stress Inventory (OSI-R) developed by Osipow in was used for the questionnaire survey . It consThis study used the Symptoms Checklist 90 (SCL-90) , which iThis study used the Pittsburgh Sleep Quality Index (PSQI) compiled by Buysse et al. . The PSQThe levels of IL-2, IL-6, IL-8, and TNF-α in the oil workers were determined by enzyme-linked immunosorbent assay . After collection, whole blood samples were centrifuged for 7 min (3000 RPM), and the supernatant stored at −80°C. Samples were transported at low temperature to avoid repeated freeze–thaw cycles.(1) Epidemiological survey quality control: the investigators were trained before participating in the survey and were familiar with the questionnaire content and work processes. Before the survey, the researchers explained the content and answer method of the questionnaire in detail. The questionnaires were collected on the spot, and incomplete questionnaires were eliminated after collection.(2) Laboratory quality control: blood samples were collected by nurses in the hospital. A pre-experiment and a follow-up experiment were carried out. The experimental steps were carried out in strict accordance with the instructions of the kit.t-test was used for comparison of means between two groups, and the χ2-test for comparison of rates, followed by Pearson correlation analysis. Multivariate analysis and interaction analysis for factors affecting sleep disorders were conducted by binary logistic regression analysis. Amos 25.0 software was used to establish the structural equation model and analyze the path coefficients between variables. The maximum likelihood method was used to estimate the model, and the final model was obtained after repeated iterative modification according to the modified index. Indirect effects were tested using the non-parametric percentile Bootstrap method with bias correction. When χ2/df ≤ 5.000, root mean square error of approximation (RMSEA) < 0.080, normalized Fit index (NFI), relative fit index (RFI), incremental fit index (IFI), Tucker-Lewis Index (TLI), and comparative fit index (CFI) were all >0.900, this indicated that all fitting indexes of the model were within the acceptable range. The significance level was α = 0.05.The data were entered into the Epidata 3.0 database; SPSS version 22.0 software  was used for the statistical analysis. If the measurement data followed a normal distribution and had uniform variance, The demographic characteristics of the participants are shown in P < 0.05). In this survey, 553 people (48.5%) suffered from mental disorders, and the incidence of mental disorders was higher among oil workers with older age, higher education, and longer service life, and among oil transport workers, shift workers and married workers. In this survey, 646 individuals (56.6%) suffered from sleep disorders; the incidence of sleep disorders differed according to sex, age, professional title, working years, type of work, and shift situation (P < 0.05)  had low occupational stress, 328 (28.7%) had moderate occupational stress, and 704 (61.7%) had high occupational stress. There were differences in occupational stress among workers of different ages, educational background, professional title, working years, shift work, and marital status ( < 0.05) .P < 0.05), and the PRQ was negatively correlated with sleep quality (P < 0.05). There was a positive correlation between mental health score and sleep quality (P < 0.05)  .With sleep quality as the dependent variable , general demographic characteristics, occupational stress and mental disorders were included in the equation as independent variables, and binary logistic regression analysis was conducted. The analysis showed that age (30–45 years) , college degree or above , borehole operation , drilling , extraction of oil , shift work , occupational stress , and mental disorders  were risk factors for sleep disorders .P < 0.05)  .With sleep quality as the dependent variable , occupational stress, mental disorder and cytokines significant in the univariate analysis  were incBased on the above multivariate logistic regression analysis of sleep disorders, the effects of occupational stress, mental disorder and cytokine interactions on sleep disorders were analyzed. The group with high occupational stress and mental disorder were taken as the reference group. The effects of IL-2 × low occupational stress, IL-2 × moderate occupational stress and IL-2 × non-mental disorders on sleep disorders were analyzed. The results showed that IL-2 × moderate occupational stress  and IL-2 × non-mental disorders  were protective factors for the occurrence of sleep disorders when compared with high occupational stress and mental disorders .2/df = 2.638, RMSEA = 0.069, NFI = 0.916, RFI = 0.902, IFI = 0.946, TLI = 0.937, CFI = 0.946: all fitting indexes were within the acceptable range, indicating that the model fitted well. Occupational stress and mental health had positive predictive effects on IL2 level and sleep quality , indicating that the higher the occupational stress level and the more serious the psychological disorder, the higher the IL2 concentration, and the worse the sleep quality. In addition, occupational stress had a direct positive predictive effect on psychological disorders (β = 0.25), indicating that the higher the level of occupational stress, the more serious the psychological disorder. Sleep disturbance had a direct negative predictive effect on IL2 concentration (β = −0.21), indicating that the worse the sleep quality, the lower the IL2 concentration (The results of the structural equation analysis showed that the χntration . The totSleep is closely related to people’s health and is an important prerequisite to ensure the normal working of the body. For professional people in particular, a good sleep can make them energetic, with higher work efficiency. Therefore, identifying the risk factors that may affect sleep can provide some help in improving the sleep quality of workers. A previous study on the sleep of oil workers found that age and shift work were the factors influencing sleep disorders, but this study focused on analyzing the mediating effect of sleep disorders in the influence of gender and age on hypertension, and did not conduct an in-depth study on the factors influencing sleep disorders in oil workers . TherefoThe study found that the incidence of sleep disorders varied by age, education, shift work and type of work. This is the same conclusion as some previous studies –33. In aThe study has found that there is a relationship between immune function and sleep, and cellular immune factors may be involved in sleep regulation . IL-2 isThis research identifies that, in addition to demographic characteristics, occupational stress, mental health and cytokine levels also affect the sleep quality of oil workers. Occupational stress and mental disorders were risk factors for sleep disorder, and that the level of IL-2 was a protective factor for sleep disorder. The lower the IL-2 level, the higher the risk of sleep disorder. Low occupational stress and the interaction between mental health and IL-2 may reduce the risk of sleep disorders.This study provides a reliable basis to help employers to develop strategies to improve workers’ mental health and sleep quality. It is suggested that employers should reduce the stress suffered by workers and improve their mental health to reduce the occurrence of sleep problems. In this study, cytokine levels were used as sleep-related predictors to evaluate workers’ sleep quality.The disadvantages of this study are as follows: First, as a special occupational group, oil workers have a higher labor intensity and a more difficult working environment than general workers. Therefore, the conclusions of this study need to be further verified in other occupational groups. Second, this study is a cross-sectional study, so it is difficult to infer causality. Finally, a total of four cytokines were measured in this study, but only IL-2 was associated with sleep according to the multivariate analysis. However, the other three cytokines were also associated with sleep in other studies. Therefore, the relationship between these cytokines and sleep will be further investigated in subsequent studies.The original contributions presented in this study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.This study was approved by the Ethics Committee of Xinjiang Medical University. The patients/participants provided their written informed consent to participate in this study.XL, QX, and XY contributed to the acquisition, analysis, and interpretation of data. All authors contributed substantially to the work presented in this manuscript, were involved in drafting the manuscript and revising it for important intellectual content, and reviewed and approved the final manuscript. XL, QX, and JL conceived and designed the study.