Association of Opioid Administration During General Anesthesia and Survival for Severely Injured Trauma Patients: A Preplanned Secondary Analysis of the PROPPR Study.

BACKGROUND: There is a lack of reported clinical outcomes after opioid use in acute trauma patients undergoing anesthesia. Data from the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study were analyzed to examine opioid dose and mortality. We hypothesized that higher dose opioids during anesthesia were associated with lower mortality in severely injured patients. METHODS: PROPPR examined blood component ratios in 680 bleeding trauma patients at 12 level 1 trauma centers in North America. Subjects undergoing anesthesia for an emergency procedure were identified, and opioid dose was calculated (morphine milligram equivalents [MMEs])/h. After separation of those who received no opioid (group 1), remaining subjects were divided into 4 groups of equal size with low to high opioid dose ranges. A generalized linear mixed model was used to assess impact of opioid dose on mortality (primary outcome, at 6 hours, 24 hours, and 30 days) and secondary morbidity outcomes, controlling for injury type, severity, and shock index as fixed effect factors and site as a random effect factor. RESULTS: Of 680 subjects, 579 had an emergent procedure requiring anesthesia, and 526 had complete anesthesia data. Patients who received any opioid had lower mortality at 6 hours (odds ratios [ORs], 0.02-0.04; [confidence intervals {CIs}, 0.003-0.1]), 24 hours (ORs, 0.01-0.03; [CIs, 0.003-0.09]), and 30 days (ORs, 0.04-0.08; [CIs, 0.01-0.18]) compared to those who received none (all P < .001) after adjusting for fixed effect factors. The lower mortality at 30 days in any opioid dose group persisted after analysis of those patients who survived >24 hours (P < .001). Adjusted analyses demonstrated an association with higher ventilator-associated pneumonia (VAP) incidence in the lowest opioid dose group compared to no opioid (P = .02), and lung complications were lower in the third opioid dose group compared to no opioid in those surviving 24 hours (P = .03). There were no other consistent associations of opioid dose with other morbidity outcomes. CONCLUSIONS: These results suggest that opioid administration during general anesthesia for severely injured patients is associated with improved survival, although the no-opioid group was more severely injured and hemodynamically unstable. Since this was a preplanned post hoc analysis and opioid dose not randomized, prospective studies are required. These findings from a large, multi-institutional study may be relevant to clinical practice.

Risk of neuroblastoma, birth-related characteristics, congenital malformations and perinatal exposures: A pooled analysis of the ESCALE and ESTELLE French studies (SFCE).

Neuroblastoma (NB), an embryonic tumour arising from neural crest cells, is the most common malignancy among infants. The aetiology of NB is largely unknown. We conducted a pooled analysis to explore whether there is an association between NB and preconception and perinatal factors using data from two French national population-based case-control studies. The mothers of 357 NB cases and 1783 controls younger than 6 years, frequency-matched by age and gender, responded to a telephone interview that focused on demographic, socioeconomic and perinatal characteristics, childhood environment, life-style and maternal reproductive history. Unconditional logistic regression was used to estimate pooled odds ratios and 95% confidence intervals. After controlling for matching variables, study of origin and potential confounders, being born either small (OR 1.4 95% CI 1.0-2.0) or large (OR 1.5 95% CI 1.1-2.2) for gestational age and, among children younger than 18 months, having congenital malformations (OR 3.6 95% CI 1.3-8.9), were significantly associated with NB. Inverse associations were observed with breastfeeding (OR 0.7 95% CI 0.5-1.0) and maternal use of any supplements containing folic acid, vitamins or minerals (OR 0.5 95% CI 0.3-0.9) during the preconception period. Our findings reinforce the hypothesis that fetal growth anomalies and congenital malformations may be associated with an increased risk of NB. Further investigations are needed in order to clarify the role of folic acid supplementation and breastfeeding, given their potential importance in NB prevention.

The Operating and Anesthetic Reference Assistant (OARA): A fine-tuned large language model for resident teaching.

OBJECTIVE: This study aimed to fine-tune a large language model (LLM) for domain-specific text generation in surgical and anesthesia residency education. SUMMARY BACKGROUND DATA: With growing interest in artificial intelligence (AI) for medical training, the potential of LLMs to transform residency education is explored. METHODS: The 7-billion parameter base model "Vicuna v1.5" was trained on 266,342 lines of text from 821 peer-reviewed documents. We evaluated the model with 150 surgical or anesthesia queries and assessed accuracy, token count, and inference speed across various reasoning tasks. Tests of significance were conducted using ANOVA and chi-square analysis. RESULTS: Our model achieved 65.3% accuracy, excelling in surgical case-based tasks. We found no significant difference in accuracy between knowledge domains (P=0.081), though longer response generation demonstrated poorer accuracy, with significant accuracy variation based on output length (P â€‹= â€‹0.002). CONCLUSIONS: LLMs show potential in enhancing residency education. Our model's efficiency and task-specific accuracy highlights such promise, though limits in parameter count diminishes accuracy of longer response generation. Our findings showcase how AI may be integrated effectively within future residency training.

Volatile anesthetic and outcome in acute trauma care: planned secondary analysis of the PROPPR study.

Background: This retrospective analysis of prospectively collected data from the PROPPR study describes volatile anesthetic use in severely injured trauma patients undergoing anesthesia. Methods: After exclusions, 402 subjects were reviewed of the original 680, and 292 had complete data available for analysis. Anesthesia was not protocolized, so analysis was of contemporary practice. Results: The small group who received no volatile anesthetic (n = 25) had greater injury burden (Glasgow Coma Scale P = 0.05, Injury Severity Score P = 0.001, Revised Trauma Score P = 0.03), higher 6- and 24-hour mortality (P < 0.001), and higher incidence of systemic inflammatory response syndrome (P = 0.003) and ventilator-associated pneumonia (P = 0.02) than those receiving any volatile (n = 267). There were no differences in mortality between volatile agents at 6 hours (P = 0.51) or 24 hours (P = 0.35). The desflurane group was less severely injured than the isoflurane group. Mean minimum alveolar concentration was < 0.6 and lowest in the isoflurane group compared to the sevoflurane and desflurane groups (both P < 0.01). The incidence of systemic inflammatory response syndrome was lower in the desflurane group than in the isoflurane group (P = 0.007). Conclusion: In this acutely injured trauma population, choice of volatile anesthetic did not appear to influence short-term mortality and morbidity. Subjects who received no volatile were more severely injured with greater mortality, representing hemodynamic compromise where volatile agent was limited until stable. As anesthetic was not protocolized, these findings that choice of specific volatile was not associated with short-term survival require prospective, randomized evaluation.

[Antineoplastic drug-induced nausea and vomiting in pediatric onco-hematology: 2022: Guidelines from the supportive care committee of the French Society of Childhood Cancer (SFCE)]. / Nausées-vomissements induits par les traitements anticancéreux (NVITAC) en onco-hématologie pédiatrique : recommandations 2022 du Comité soins de support de la SFCE.

Nausea and vomiting induced by cancer treatment (CINV) remain one of the most common and feared side effects in children despite the use of new drugs to prevent them. The existing recommendations for the prophylaxis and treatment of CINV are based on adult patients in Anglo-Saxon societies. Based on a recent review of the literature, we focused on specific pediatric issues in order to offer recommendations validated by the supportive care committee of the French society for childhood cancer.

Low-dose ketamine adjuvant treatment for refractory pain in children, adolescents and young adults with cancer: a pilot study.

OBJECTIVES: Ketamine, an N-methyl-D-aspartate receptor antagonist, is effective at relieving adult cancer pain, although there have been very few reports to date regarding its use in children and in adolescents and young adults (AYA). This study assessed the efficacy, safety and opioid-sparing effects of low doses of ketamine added to opioid analgesics to alleviate persistent cancer pain. METHODS: This prospective, multicentre, observational trial collected data regarding demographics, pain characteristics, pain score assessment within the first 48 hours of ketamine administration, tolerance and satisfaction from 38 patients aged 2-24 years prescribed with ketamine as an adjuvant antalgic for refractory cancer pain in 10 French paediatric oncology centres. RESULTS: The mean visual analogue scale pain score decreased from 6.7 to 4.3 out of 10 (n=39, p<0.001) from day 1 to day 3 and by at least 2 points in 56% of the patients (n=22) 48 hours after initiation of ketamine. Nine patients experienced poor tolerance (≥2 side effects), all with infusion rates lower than 0.05 mg/kg/hour. None had limiting toxicities. An opioid-sparing effect was highlighted in four patients. Fifty-four per cent of the prescribers and 47% of the patients found the addition of ketamine 'very helpful'. CONCLUSIONS: Low doses of ketamine as an adjuvant to opioids significantly reduced the intensity of pain in half of the study population. A tendency towards better pain control is shown, although a lack of statistical power somewhat limits our conclusions, especially in children. Nevertheless, ketamine may be a useful option for improving the treatment of refractory pain in children and AYA with cancer.

Self-Representations of Military Veterans Suffering From Chronic Post-traumatic Stress Disorder: The Role of Sport.

Background: Post-traumatic stress disorder (PTSD) is a psychiatric illness that is very prevalent in both civilian and military environments. The clinical course, regardless of management, is chronic for a number of patients, especially veterans. Persistent PTSD symptoms interact with representations of the person and their body, and may negatively impact rehabilitation. Sport is known to help psychiatric patients such as those suffering from PTSD, as it improves the connection with the body, and supports physiological and emotional regulation. However, the impact of sport on self-representations has not yet been studied. The first aim of this study is to explore person and body representations in a population of military veterans suffering from chronic PTSD, as a function of clinical severity. Second, it aims to explore how a 9-day sport program, which includes an element of socio-professional rehabilitation, changes representations of the person and their body. Methods: This exploratory qualitative study examined the self-representation of veterans with chronic PTSD before a sport rehabilitation program. Veterans were given the prompts "body" and "person" and asked to free associate. PTSD severity and the mind-body connection were assessed using the Posttraumatic Stress Disorder Checklist for DSM-5, and the Freiburg Mindfulness Inventory, respectively. Parasympathetic activity was recorded at rest. A subgroup of the population volunteered to participate in a post-program session to record the same semantic, psychological, and physiological variables. Results: Although before the program, veterans gave more negatively than positively valenced words, no relation was observed between the overall number of negative words and PTSD severity. Post-program, changes were observed in terms of valence. Specifically, some negatively-valenced categories of words disappeared, and some positive categories appeared. At the same time, there was a fall in PTSD severity, an increase in the mind-body connection, and a decrease in parasympathetic activation. Conclusions: This study highlighted that veterans with chronic PTSD have a negative representation of the self. A dedicated, 9-day program that included regular sport improved self-representations related to both the person and their body, and reduced PTSD symptoms. The findings underline the importance of ensuring that programs for patients suffering from chronic PTSD should include sporting activity, and highlight the benefits. Sport appears to be a path to the reappropriation of a positive image of the self, by improving the representation of the body. This relationship could be consistent with improved interoception, but our results need further investigation.

Increased risk of bone tumors after growth hormone treatment in childhood: A population-based cohort study in France.

The association between growth hormone (GH) treatment and cancer risk has not been thoroughly evaluated and there are questions about any increased risk of bone tumors. We examined cancer risk and especially bone tumor risk in a population-based cohort study of 6874 patients treated with recombinant GH in France for isolated GH deficiency, short stature associated with low birth weight or length or idiopathic short stature. Adult mortality and morbidity data obtained from national databases and from questionnaires. Case ascertainment completeness was estimated with capture-recapture methods. Standardized mortality and incidence ratios were calculated using national reference data. 111 875 person-years of observation were analyzed and patients were followed for an average of 17.4 ± 5.3 years to a mean age of 28.4 ± 6.2 years. For cancer overall, mortality and incidence were not different from expected figures. Five patients developed bone tumors (chondrosarcoma, 1, Ewing sarcoma, 1, osteosarcoma, 3) of whom 3 died (Ewing sarcoma, 1, osteosarcoma, 2), whereas only 1.4 case and 0.6 deaths were expected: standardized mortality ratio, 5.0 and standardized incidence ratio from 3.5 to 3.8 accounting or not accounting for missed cases. Most patients received conventional doses of GH, although one patient with osteosarcoma had received high dose GH (60 µg/kg/d). This study confirms an increased risk of bone tumors but not overall cancer risk in subjects treated with GH in childhood for isolated GH deficiency or childhood short stature. Further work is needed to elucidate the mechanisms involved.

Does ATRX germline variation predispose to osteosarcoma? Three additional cases of osteosarcoma in two ATR-X syndrome patients.

Osteosarcoma is the most common malignant bone tumor in adolescents and young adults. Most osteosarcomas are sporadic but the risk of osteosarcoma is also increased by germline variants in TP53, RB1 and RECQL4 genes. ATRX germline variations are responsible for the rare genetic disorder X-linked alpha-thalassemia mental retardation (ATR-X) syndrome characterized by severe developmental delay and alpha-thalassemia but no obvious increased risk of cancer. Here we report two children with ATR-X syndrome who developed osteosarcoma. Notably, one of the children developed two osteosarcomas separated by 10 years. Those two cases raise the possibility that ATRX germline variant could be associated with an increased risk of osteosarcoma.

[Care pathways before diagnosis in children and adolescents with malignancies]. / Parcours prédiagnostique des enfants et adolescents atteints de tumeurs solides.

OBJECTIVE: to describe medical care pathways between first symptoms and first oncologic consultation in children and adolescents with solid cancers in order to analyze a possible relationship between delayed diagnosis and its potential consequences. METHODS: Retrospective study on patients aged less than 25 years at first consultation in the oncology department of pediatric, adolescent and young adult in Institut Curie during one year. Were collected data on cancer characteristics, components of care pathways, and sociodemographic parents' characteristics. RESULTS: Hundred and six patients were selected, with median age of 6 years. Most represented tumor was low-grade cerebral tumor (17.0%). Pain was the most frequent type of disorder observed as first sign (34.3% of patients). First signs were unspecific in only 27.6% of cases. Most patients were first seen by a general practitioner (29.3%). Median total time to diagnosis was one month [ranges: 0-64]. Median number of consultations before referral to oncology expert was 2 [0-7]. Retrospective analysis found a possible delayed diagnosis in 44.3% of patients, with potential vital and functional risks estimated respectively at 14.1 and 20.7% of overall population. Time to diagnosis was shorter if father was of foreign nationality vs. French (34 days vs. 72 days, P<0.05), and longer if parents were separated (74.5 days vs. 42.5 days, P<0.03). CONCLUSIONS: Overall time to diagnosis is quite fast, even if first signs of pediatric cancers are very polymorphic. Some medical and sociodemographic factors could influence characteristics of care pathways.

A Retrospective Multicentric Study of Ewing Sarcoma Family of Tumors in Patients Older Than 50: Management and Outcome.

Ewing's sarcoma family of tumors (EFTs) is a group of rare and aggressive tumors. Data on EFTs in patients (pts) ≥ 50 years are limited and these pts are often not eligible for clinical trials. Some, but not all, studies have reported inferior outcome for older pts with EFTs. We conducted an IRB-approved retrospective analysis among centers of the French Sarcoma Group on pts diagnosed with EFTs at age ≥50 between 2000 and 2012. Clinical features, treatment modality and outcomes were analyzed. Seventy-seven pts were identified, including 36 females (46.8%) and the median age at diagnosis was 56 years (range: 50-86). The primary tumor was located in soft tissue in 59 pts (76.6%). Fifty-six pts (72.7%) had localized disease, among them 49 (87.5%) received chemotherapy in addition to local therapy. Their estimated 3-yr OS and event-free survival (EFS) rates were respectively 73.3% and 62.2%. Recurrence occurred in 43 pts. The estimated 3-yr OS rate was 37% in pts with metastatic disease at presentation. EFTs in pts ≥50 years are more likely to originate from soft tissue and their outcomes appear to be worse than that of younger pts treated with modern protocols.

[Adolescents and young adults with cancer between adaptation and addiction: state of the question]. / Adolescents et jeunes adultes atteints de cancer, entre adaptation et addiction: un état de la question.

The purpose of this literature review is to make a point on the state of health of adolescents and young adults (15-25 years) suffering from cancer. The adaptation strategies and the impact of the announcement of cancer will be discussed. In addition, we are going to consider the characteristics of teenagers and young adults, given the fact that development is still in progress. This period is especially punctuated by various experiments and the emergence of some clinical signs. Also, we have identified various studies concerning the use of licit and illicit substances. Furthermore, we have taken interest in behavioral addictions, particularly cyber addiction. While trying to cross these variables with a population of teenagers and young adults in the context of somatic diseases, it occurred that this population was not well known and studied. The interest of this synthesis is to underline the importance to make future researches in these perspectives.

Prevalence of smoking in psychiatric patients.

Compelling evidence that tobacco-smoking is a form of drug addiction exists. The aim of this study is to determine the following: (1) prevalence of tobacco-smoking and of nicotine dependence in French psychiatric patients; (2) rates and patterns of tobacco smoking and of nicotine dependence according to diagnosis; (3) relationship between current smoking status and antipsychotic medications; and (4) relationship between cigarette smoking and neurological side effects induced by neuroleptics. A population of 711 psychiatric in- and outpatients was assessed using: (1) a detailed smoking self-questionnaire for smoking history and nicotine dependence; and (2) a questionnaire for staff covering treatments and DSMIII-R diagnoses. Data were analyzed using chi2 analysis of variance (ANOVA) tests (one factor) for quantitative comparisons between groups of patients, and analysis of covariance (ANCOVA) test with age covariate was performed for age-dependent variables. Prevalence of smoking in the population of psychiatric patients was significantly higher than in the French general population. Diagnoses among current smokers were mainly substance-related disorder and schizophrenia. The authors established correlations between prevalence of smoking and age, sex, marital and socioeconomic status, alcohol use, coffee consumption and other psychoactive substance use or abuse. The authors did not find relationship between smoking prevalence and institutionalization. Neuroleptic neurological side effects were significantly fewer among smokers compared to nonsmokers. However, the rate of smokers was significantly higher in psychiatric patients receiving neuroleptic drugs. Nicotine abuse in psychiatric patients, and especially in schizophrenic patients, could support the hypothesis that smoking is consistent with self-medication.

[Childhood cancer: progress but prognosis still very unequal. Example of Retinoblastoma and high-risk Neuroblastoma]. / Les tumeurs malignes de l'enfant: des progrès mais des pronostics encore très inégaux. Exemple du rétinoblastome et du neuroblastome de haut risque.

Children suffering with cancer have a higher probability of cure than adult. Since the 1950's, high cure rates have been achieved following remarkable progress in the overall care of these children. Not only children are more often "cured" than during the past century but they are probably "better cured" with the hope of experiencing less late effects. Nevertheless, there are still large disparities related to tumor diagnosis and regional area on the globe. If retinoblastoma is now cured in about 100% of the cases in industrialized countries, a different figure is seen unfortunately in economically disadvantaged countries. Not only is access to primary care lower, but also ophthalmologic techniques and available cancer treatments are less effective. Nowadays, such high cure rates observed for children with retinoblastoma are not the rule for all children with cancer. For example, despite considerable progress with new innovative treatments, the cure rate of children with metastatic neuroblastoma does not exceed 40%.