Metabolomic Analysis of Pediatric Patients with Idiosyncratic Drug-Induced Liver Injury According to the Updated RUCAM.

Hepatotoxicity, a common adverse drug effect, has been extensively studied in adult patients. However, it is equally important to investigate this condition in pediatric patients to develop personalized treatment strategies for children. This study aimed to identify plasma biomarkers that characterize hepatotoxicity in pediatric patients through an observational case-control study. Metabolomic analysis was conducted on 55 pediatric patients with xenobiotic liver toxicity and 88 healthy controls. The results revealed clear differences between the two groups. Several metabolites, including hydroxydecanoylcarnitine, octanoylcarnitine, lysophosphatidylcholine, glycocholic acid, and taurocholic acid, were identified as potential biomarkers (area under the curve: 0.817; 95% confidence interval: 0.696-0.913). Pathway analysis indicated involvement of primary bile acid biosynthesis and the metabolism of taurine and hypotaurine (p < 0.05). The findings from untargeted metabolomic analysis demonstrated an increase in bile acids in children with hepatotoxicity. The accumulation of cytotoxic bile acids should be further investigated to elucidate the role of these metabolites in drug-induced liver injury.

Raising the Bar: Multimodal Analgesia with Transdermal Lidocaine for Nuss Repair of Pectus Excavatum Decreases Length of Stay and Opioid Use.

INTRO: Pain management for minimally invasive (Nuss) repair of pectus excavatum (PE) is challenging, particularly as the judicious use of opioids has become a patient safety priority. Multi-modal pain management protocols are increasingly used, but there is limited experience using transdermal lidocaine patches (TLP) in this patient population. METHODS: Pediatric anesthesiologists and surgeons in a children's hospital within a hospital designed a multi-modal perioperative pain management protocol for patients undergoing Nuss repair of PE (IRB00068901). The protocol included use of TLP in addition to other adjuncts such as methadone, gabapentin, and NSAIDS. Following initiation of the protocol charts were reviewed retrospectively, comparing outcomes before and after implementation of the protocol. RESULTS: Forty-nine patients underwent a Nuss procedure between 2013 and 2022, 15 prior to initiation of the protocol and 34 after. Patient demographics and operative length were similar between the two groups. Average length of stay decreased from 4.7 to 3.3 days and reported opioid use at the time of the first outpatient post-op visit dropped from 60% to 24% (p < 0.05). Morphine milligram equivalents (MME) usage was decreased following implementation during hospital admission, at discharge, and at first post-operative visit (464 vs. 169, 1288 vs. 218, and 214 vs. 56, respectfully, p < 0.05). There were no ED visits or readmissions <30 days related to post-operative pain. CONCLUSION: Post-operative opioid usage and hospital length of stay were decreased after initiation of the protocol. Transdermal lidocaine patches may be a helpful adjunct to minimize narcotic requirements after repair of pectus excavatum. LEVEL OF EVIDENCE: Level II.

Acute physiological responses to a pyramidal exercise protocol and the associations with skin temperature variation in different body areas.

This study aimed to examine the skin temperature (Tsk) variations in five regions of interest (ROI) to assess whether possible disparities between the ROI's Tsk could be associated with specific acute physiological responses during cycling. Seventeen participants performed a pyramidal load protocol on a cycling ergometer. We synchronously measured Tsk in five ROI with three infrared cameras. We assessed internal load, sweat rate, and core temperature. Reported perceived exertion and calves' Tsk showed the highest correlation (r = -0.588; p < 0.01). Mixed regression models revealed that the heart rate and reported perceived exertion were inversely related to calves' Tsk. The exercise duration was directly associated with the nose tip and calf Tsk but inversely related to the forehead and forearm Tsk. The sweat rate was directly related to forehead and forearm Tsk. The association of Tsk with thermoregulatory or exercise load parameters depends on the ROI. The parallel observation of the face and calf Tsk could indicate simultaneously the observation of acute thermoregulatory needs and individual internal load. The separate Tsk analyses of individual ROI appear more suitable to examine specific physiological response than a mean Tsk of several ROI during cycling.

The relation between activator and inhibitor killer-cell immunoglobulin-like receptors and hepatotoxicity in oncological treatment.

BACKGROUND: The molecular interactions between killer-cell immunoglobulin-like receptors (KIRs) and their related HLA class I ligands play a central role in regulating the responses of natural killer (NK) cells. Our study aim was to determine the role played by KIR genes and their HLA ligands in the genetic predisposition for the development of hepatotoxicity in children treated with chemotherapy for an oncological process. METHODS: The study group was composed of 22 children with cancer, being treated with chemotherapy at the Unit of Pediatric Oncology of the Maternity Hospital Virgen de las Nieves (Granada, Spain) and presenting signs of drug-induced liver injury (DILI). Twenty-four children receiving similar treatment but presenting no signs of DILI were selected as a control group. RESULTS: The children with the KIR K2DS2 were four times more likely to have hepatotoxicity (OR=4.08, P=0.034, 95% CI: 1.1-15). The patients with 2DS2 and the C1 ligand were ten times more likely to undergo an episode of hepatotoxicity (P=0.007). CONCLUSIONS: KIRs may be risk factors for susceptibility to hepatotoxicity following chemotherapy.

Pediatric Practitioner Knowledge of Arsenic in Baby Food.

OBJECTIVE: Rice, one of the first solid foods introduced to infants, is 10 times more absorbent of inorganic arsenic than any other grain. An evaluation has not been performed about practitioner knowledge of arsenic content in infant foods. The purpose of this survey was to determine pediatric practitioners' knowledge of current US Food and Drug Administration (FDA) recommendations to limit exposure to arsenic-containing foods in infants. METHODS: This was a convenience sample of pediatric practitioners conducted as an online survey. The survey contained 19 questions related to knowledge of arsenic-containing foods, FDA recommendations, practitioner recommendations on feeding infants, and demographic information. Participants were recruited using organization list servs. Participants were reminded to complete the survey 2 months after the initial email. An infographic on arsenic was provided at the end of the survey. RESULTS: One hundred thirty-seven individuals completed the survey. The majority of respondents were physicians or pharmacists and have been in practice less than 6 years. Nine percent of respondents (11/123) stated the FDA arsenic limit of 100 ppb. Sixteen percent (20/123) identified white rice as having a lower inorganic arsenic content than brown rice and 27% (36/132) identified that there is no difference in inorganic arsenic content between organic infant rice cereal and conventional infant rice cereal. CONCLUSIONS: The vast majority of participants were not aware of the FDA's proposed limit on arsenic consumption or the concern of heavy metals in baby foods. More education is needed to increase knowledge regarding arsenic in baby foods.

A large epidemic of a necrotic skin infection in the Democratic Republic of São Tomé and Principe: an epidemiological study.

INTRODUCTION: In 2016-18, the Democratic Republic of São Tomé and Príncipe suffered a necrotic skin infection epidemic. METHODS: A surveillance system was established after increased hospitalisations for this infection. Microbiology results were available for samples analysed in December 2016 and March 2017 using whole genome sequencing and metagenomics. Negative binomial regression was used to study the association of weather conditions with monthly case counts in a time-series analysis. RESULTS: From October 2016 to October 2018, the epidemic cumulative attack rate was 1.5%. The first peak lasted 5 months, accounting for one-third of total cases. We could not conclusively identify the aetiological agent(s) due to the country's lack of microbiology capacity. Increased relative humidity was associated with increased monthly cases (incidence rate ratio (IRR) 1.05, 95% CI 1.02-1.09), and higher precipitation in the previous month with a higher number of cases in the following month (months with 0-49 mm rainfall compared with months with 50-149 mm and ≥150 mm: IRR 1.44, 95 % CI 1.13-1.78 and 1.50, 95% CI 1.12-1.99, respectively). DISCUSSION: This epidemic was favoured by increased relative humidity and precipitation, potentially contributing to community-based transmission of ubiquitous bacterial strains superinfecting skin wounds. FUNDING: World Health Organization Regional Office for Africa, Ministry of Health.

Lesión hepática inducida por quimioterapia en niños / Chemotherapy-induced liver injury in children

Introducción: La lesión hepática inducida por fármacos debida a quimioterapia es una causa importante de morbilidad en enfermos oncológicos aunque sus manifestaciones clínicas son poco conocidas. Objetivo: El objetivo del presente estudio fue determinar las características (formas de presentación, gravedad y tipo de lesión) de la hepatotoxicidad por quimioterapia en niños tratados por cáncer. Pacientes y método: Se incluyó en el estudio a un total de 22 enfermos oncológico en los que, tras descartar otras causas de aumento de transaminasas (infecciosa, metabólica, autoinmune o hereditaria), se concluye, según la escala de causalidad CIOMS, que se trata de un episodio posible, probable o definido de lesión hepática por fármacos. Resultados: Todos los niños tuvieron más de un episodio de hepatotoxicidad, en total se analizan 98 episodios. Metotrexato fue el fármaco implicado con mayor frecuencia. El patrón histológico de daño predominante fue hepatocelular. Solo 2 episodios fueron clasificados de graves. Conclusiones: La hepatotoxicidad idiosincrásica por quimioterapia es frecuente, la tendencia es a la recidiva con la reexposición y, aunque no suele tener consecuencias importantes, la elevada frecuencia hace aconsejable establecer algoritmos de seguridad estandarizados con controles muy estrictos de enzimas hepáticas durante los períodos de alto riesgo de quimioterapia

Introduction: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood. Objective: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer. Patients and method: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs. Results: All children had more than one episode of hepatotoxicity, and a total of 98 episodes are analysed. Methotrexate was the most commonly implicated drug. The histological pattern of predominant damage was hepatocellular. Only 2episodes were classified as serious. Conclusions: Idiosyncratic hepatotoxicity due to chemotherapy is frequent, with a tendency to relapse with re-exposure. Although it does not usually have important consequences, the high frequency makes it advisable to establish standardised safety algorithms with very strict monitoring of liver enzymes during high periods of risk in chemotherapy

[Chemotherapy-induced liver injury in children]. / Lesión hepática inducida por quimioterapia en niños.

INTRODUCTION: Drug-induced liver injury due to chemotherapy is an important cause of morbidity in cancer patients, although its clinical manifestations are poorly understood. OBJECTIVE: The objective of the present study was to determine the characteristics (forms of presentation, severity, and type of injury) of hepatotoxicity due to chemotherapy in children treated for cancer. PATIENTS AND METHOD: A total of 22 oncological patients were included in the study, after ruling out other causes of increased transaminases (infectious, metabolic, autoimmune, or hereditary), according to the CIOMS causality scale, it is concluded that it was a possible, probable or definite episode of hepatic injury by drugs. RESULTS: All children had more than one episode of hepatotoxicity, and a total of 98 episodes are analysed. Methotrexate was the most commonly implicated drug. The histological pattern of predominant damage was hepatocellular. Only 2episodes were classified as serious. CONCLUSIONS: Idiosyncratic hepatotoxicity due to chemotherapy is frequent, with a tendency to relapse with re-exposure. Although it does not usually have important consequences, the high frequency makes it advisable to establish standardised safety algorithms with very strict monitoring of liver enzymes during high periods of risk in chemotherapy.

Correlation between Topographic Parameters Obtained by Back Surface Topography Based on Structured Light and Radiographic Variables in the Assessment of Back Morphology in Young Patients with Idiopathic Scoliosis.

STUDY DESIGN: Optical cross-sectional study. PURPOSE: To study the correlation between asymmetry of the back (measured by means of surface topography) and deformity of the spine (quantified by the Cobb angle). OVERVIEW OF LITERATURE: The Cobb angle is considered the gold standard in diagnosis and follow-up of scoliosis but does not correctly characterize the three-dimensional deformity of scoliosis. Furthermore, the exposure to ionizing radiation may cause harmful effects particularly during the growth stage, including breast cancer and other tumors. METHODS: Patients aged 13.15±1.96 years (range, 7-17 years; n=88) with Cobb angle greater than 10° were evaluated with X-rays and our back surface topography method through three variables: axial plane (DHOPI), coronal plane (POTSI), and profile plane (PC). Pearson's correlation was applied to determine the correlation between topographic and radiographic variables. One-way analysis of variance and Bonferroni correction were used to compare groups with different grades of scoliosis. Significance was set at p<0.01 and, in some cases, at p<0.05. RESULTS: We detected a positive, statistically significant correlation between Cobb angle with DHOPI (r=0.810) and POTSI (r=0.629) and between PC variables with thoracic kyphosis angle (r=0.453) and lordosis lumbar angle (r=0.275). In addition, we found statistically significant differences for DHOPI and POTSI variables according to the grade of scoliosis. CONCLUSIONS: Although the back surface topography method cannot substitute for radiographs in the diagnosis of scoliosis, correlations between radiographic and topographic parameters suggest that it offers additional quantitative data that may complement radiologic study.

Clinical application of back surface topography by means of structured light in the screening of idiopathic scoliosis.

We present the results of the clinical validity in the screening of idiopathic scoliosis with a nonharming method of back surface topography by means of structured light projection. A total of 155 patients were evaluated (mean age 13.3 years). They were divided into two groups: pathologic patients (scoliosis) and nonpathologic patients (control and asymmetries). An analytical case-control study was carried out. Our topographic method obtained 92% sensitivity and 74% specificity as a screening test in identifying patients with scoliosis (P=0.05). We could quantify the vertebral deformity of scoliosis in the three spatial planes by means of three topographic variables, Horizontal Plane Deformity Index, Posterior Trunk Symmetry Index and Columnar Profile, and to elaborate a combined screening algorithm with good reliability parameters.

Quantification of topographic changes in the surface of back of young patients monitored for idiopathic scoliosis: correlation with radiographic variables.

Idiopathic scoliosis requires a close follow-up while the patient is skeletally immature to detect early progression. Patients who are monitored by radiographs are exposed to high doses of ionizing radiation. The purpose of this study is to evaluate if an optic noninvasive method of back surface topography based on structured light would be clinically useful in the follow-up of young patients with idiopathic scoliosis. This could reduce the number of radiographs made on these children. Thirty-one patients with idiopathic scoliosis were submitted twice to radiograph and our topographic method at intervals of 6 months to 1 year. Three topographical variables were applied horizontal plane deformity index (DHOPI), posterior trunk symmetry index (POTSI), and columnar profile (PC). A statistically significant correlation was found between variations of Cobb angle with DHOPI (r=0.720, p<0.01) and POTSI (r=0.753, p<0.01) during the monitoring period. Hence, this topographic method could be useful in clinical practice as an objective adjuvant tool in routine follow-up of scoliosis.

The effect of single-sex wards in mental health.

BACKGROUND: The need for single-sex accommodation in mental health trusts has been widely expressed in documents from the NHS Executive and in national and local policies. This case study describes the effects of changing two mixed-sex wards into single-sex wards. METHODS: Two mixed-sex inpatient wards were reorganised into two single-sex wards. Qualitative data on staff views was gained from semi-structured interviews and collected. RESULTS: Staff and patients appear to have made the transition from mixed to single-sex wards with relatively few problems. Staff described differences emerging between the male and female wards, with the male ward becoming calmer, while the female ward became more disruptive. CONCLUSIONS: Overall, the implementation was successful. We suggest that in general single-sex wards are just as effective as mixed-sex wards and, in some respects, may be better.

Preliminary studies of neurosensory and cardiopulmonary health compromise in captive- bred Rhesus macaques (Macaca mulatta) suffering scoliosis.

BACKGROUND: It has been widely documented that quadrupedal animals rarely display natural spontaneous scoliotic rachis deviations of the spinal column. The objective was to determine spinal deformities developed by geriatric monkeys of the Macaca mulatta species, by radiographical and tomographical studies of the vertebral column correlating morphological changes with altered physiological parameters and electrical neurosensorial conductivity of somatosensory-evoked potentials (SEPs). MATERIALS AND METHODS: A cohort of six geriatric monkeys was used: three non-scoliotic subjects and three monkeys with naturally acquired true scoliosis. RESULTS: Radiographic and tomographic studies depicted a thoracic curvature displaying a left-sided thoracic vertebral rotation. The evaluation of physiological parameters demonstrated significant differences in the respiratory rate, as it was observed for the diastolic blood pressures, which showed a decrease in the monkeys with scoliosis compared with healthy monkeys. Regarding the SEPs studies, the non-parametric test for independent samples Mann-Whitney U test displayed a significant difference observed at the left and right thoracic derivative in P1; while regarding the study of upper limbs, a significant difference was seen at the Erb's point derivative, left afferency in P1, showing in all the derivatives an increase in latency in monkeys with scoliosis versus monkeys in the control group. CONCLUSIONS: This study has demonstrated that quadrupedal animals can develop true scoliosis showing an analogous way to that occurring in humans.

Treatment of AIDS related non-Hodgkin's lymphoma with combination mitoguazone dihydrochloride and low dose CHOP chemotherapy: results of a phase II study.

PURPOSE: To evaluate the response and side effects of combination therapy with low dose CHOP chemotherapy and mitoguazone dihydrochloride in patients with non-Hodgkin's lymphoma associated with the acquired immunodeficiency syndrome (AIDS-NHL). METHODS: Eighteen patients newly diagnosed with intermediate or high-grade AIDS-NHL were treated with low dose CHOP as follows: day 1, cyclophosphamide 350 mg/m(2), intravenously (IV); doxorubicin 25mg/m(2) IV; vincristine 2mg IV; and prednisone 100mg given orally on days 1 through 5. In addition, mitoguazone dihydrochloride was given at a dose of 600 mg/m(2) IV on days 1 and 15 of each 28-day treatment cycle. RESULTS: Seventeen males and one female patient were accrued. Twelve patients had high-grade pathologies while the remainder had an intermediate grade pathology (diffuse large cell). The median CD4+ lymphocyte count was 98/dl (range 1-924). Three patients (17%) reported an AIDS-defining illness prior to lymphoma diagnosis. Of 14 evaluable patients, 6 (43%) achieved a complete remission and 5 (35%) a partial remission. The median failure free and overall survival times were 6.5 and 8.4 months, respectively. Major toxicity was hematologic with grade 3 or 4 neutropenia in 72%; two patients died of neutropenic sepsis. CONCLUSIONS: Mitoguazone in combination with low dose CHOP is a safe regimen, associated with a response rate of 79% (CR 43%, PR 36%, 95% CI=49-95%). These preliminary results suggest no major improvement in terms of response over use of CHOP without mitoguazone.

Model-based comparison of maternal and foetal organ doses from (99m)Tc pertechnetate, DMSA, DTPA, HDP, MAA and MAG(3) diagnostic intakes during pregnancy.

Organ residence times were calculated for diagnostic intakes of (99m)Tc pertechnetate, 2,3-dimercaptosuccinic acid (DMSA), diethylene triamine penta-acetic acid (DTPA), hydroxymethylene diphosphonate (HDP), macroaggregated albumin (MAA) and mercapto-acetyltriglycine (MAG(3)) during the 1st and 3rd stages of pregnancy and used with the MIRDOSE3 pregnant female phantoms for generation of dose estimates. At stage 3 individual foetal organ doses were estimated via a surrogate phantom based on that for the new-born but with mean dose/cumulated activity ( S) values scaled for compatibility with foetal whole body S. Stage 1 or 3 whole foetus doses ranged from 5.2 to 0.77 microGy MBq(-1) respectively, analogous to current ICRP estimates for these agents using similar in vivo biodistribution model databases. Most stage 3 maternal and foetal organ doses were similar within a factor of 3, being higher in the foetus than the mother with pertechnetate, DTPA and MAG(3), and lower with DMSA, HDP and MAA. Doses were more uniformly distributed among foetal organs than in the mother. Placental transfer was greatest with pertechnetate, where dose to the stage 3 foetal thyroid was 60-140 microGy MBq(-1). With each agent there was more placental transfer in stage 3 than in stage 1, but doses to stage 1 whole foetus were always higher, with the contribution from the mother dominant. For DMSA, HDP and MAG(3) the maternal contribution to total foetal body dose exceeded 93% for both stages.