Factors influencing implementation and adoption of direct oral penicillin challenge for allergy delabelling: a qualitative evaluation.

BACKGROUND: Over 95% of penicillin allergy labels are inaccurate and may be addressed in low-risk patients using direct oral penicillin challenge (DPC). This study explored the behaviour, attitudes and acceptability of patients, healthcare professionals (HCPs) and managers of using DPC in low-risk patients. METHODS: Mixed-method, investigation involving patient interviews and staff focus groups at three NHS acute hospitals. Transcripts were coded using inductive and deductive thematic analysis informed by the Theoretical Domains Framework. FINDINGS: Analysis of 43 patient interviews and three focus groups (28 HCPs: clinicians and managers) highlighted themes of 'knowledge', 'beliefs about capabilities and consequences', 'environmental context', 'resources', 'social influences', 'professional role and identity', 'behavioural regulation and reinforcement' and a cross-cutting theme of digital systems. Overall, study participants supported the DPC intervention. Patients expressed reassurance about being in a monitored, hospital setting. HCPs acknowledged the need for robust governance structures for ensuring clarity of roles and responsibilities and confidence. CONCLUSION: There were high levels of acceptability among patients and HCPs. HCPs recognised the importance of DPC. Complexities of penicillin allergy (de)labelling were highlighted, and issues of knowledge, risk, governance and workforce were identified as key determinants. These should be considered in future planning and adoption strategies for DPC.

Mortality and functional outcomes 18 months after hospitalization for COVID-19 in geriatric patients: a multicentric cohort study.

BACKGROUND: Few data are available on the long-term mortality and functional status of geriatric patients surviving after hospitalization for COVID-19. We compared the mortality and functional status 18 months after hospitalization for geriatric patients who were hospitalized for COVID-19 or another diagnosis. METHODS: This was a multicentric cohort study in Paris from January to June 2021. We included patients aged 75 years and over who were hospitalized with COVID-19 or not during this period and compared their vital and functional status 18 months after hospitalization. RESULTS: We included 254 patients (63 hospitalized for COVID-19). As compared with patients hospitalized for other reasons, those hospitalized for COVID-19 were younger (mean [SD] age 86 [6.47] vs. 88 [6.41] years, p = 0.03), less frail (median Clinical Frailty Scale score 5 [4-6] vs. 6 [4-6], p 0.007) and more independent at baseline (median activities of daily living score 5.5 [4-6] vs. 5 [3.5-6], p 0.03; instrumental activities of daily living score 3 [1-4] vs. 2 [0-3], p 0.04). At 18 months, 50.8% (n = 32/63) of COVID-19 patients had died versus 66% (n = 126/191) of non-COVID-19 patients (p 0.03). On multivariate analysis, COVID-19 positivity was not significantly associated with 18-month mortality (adjusted hazard ratio 0.67, 95% confidence interval 0.40 to 1.13). At 18 months, the two groups did not differ in activities of daily living or frailty scores. CONCLUSIONS: In this multicenter study of long-term mortality in geriatric patients discharged alive after hospitalization, positive COVID-19 status was not associated with excess mortality.

A Case Report of Fluoroscopically Guided Epidural Catheter Placement in a Parturient with History of Tethered Cord, Super-Morbid Obesity, and Risk for Difficult Airway.

Tethered cord syndrome results from adherence of the conus medullaris to the sacrum and may be associated with high complication rates from neuraxial anesthesia. We present the case of a 32-year-old gravida 2 para 0 patient with a history of lipomyelomeningocele (one of several types of spina bifida) and tethered cord status post repair, residual low-lying conus medullaris, supermorbid obesity (body mass index of 58), and Mallampati IV airway, who underwent successful fluoroscopically guided epidural catheter placement for vaginal delivery. Risks and benefits of epidural catheter utilization and methods of placement are reviewed.

Pediatric refractory chronic immune thrombocytopenia: Identification, patients' characteristics, and outcome.

Refractory chronic immune thrombocytopenia (r-cITP) is one of the most challenging situations in chronic immune thrombocytopenia (cITP). Pediatric r-cITP is inconsistently defined in literature, contributing to the scarcity of data. Moreover, no evidence is available to guide the choice of treatment. We compared seven definitions of r-cITP including five pediatric definitions in 886 patients with cITP (median [min-max] follow-up 5.3 [1.0-29.3] years). The pediatric definitions identified overlapping groups of various sizes (4%-20%) but with similar characteristics (higher proportion of immunopathological manifestations [IM] and systemic lupus erythematosus [SLE]), suggesting that they adequately captured the population of interest. Based on the 79 patients with r-cITP (median follow-up 3.1 [0-18.2] years) according to the CEREVANCE definition (≥3 second-line treatments), we showed that r-cITP occurred at a rate of 1.15% new patients per year and did not plateau over time. In multivariate analysis, older age was associated with r-cITP. One patient (1%) experienced two grade five bleeding events after meeting r-cITP criteria and while not receiving second-line treatment. The cumulative incidence of continuous complete remission (CCR) at 2 years after r-cITP diagnosis was 9%. In this analysis, splenectomy was associated with a higher cumulative incidence of CCR (hazard ratio: 5.43, 95% confidence interval: 1.48-19.84, p = 7.8 × 10-4). In sum, children with cITP may be diagnosed with r-cITP at any time point of the follow-up and are at increased risk of IM and SLE. Second-line treatments seem to be effective for preventing grade 5 bleeding. Splenectomy may be considered to achieve CCR.

Applications of Artificial Intelligence in Helicopter Emergency Medical Services: A Scoping Review.

OBJECTIVE: Recent systematic reviews of acute care medicine applications of artificial intelligence (AI) have focused on hospital and general prehospital uses. The purpose of this scoping review was to identify and describe the literature on AI use with a focus on applications in helicopter emergency medical services (HEMS). METHODS: A literature search was performed with specific inclusion and exclusion criteria. Articles were grouped by characteristics such as publication year and general subject matter with categoric and temporal trend analyses. RESULTS: We identified 21 records focused on the use of AI in HEMS. These applications included both clinical and triage uses and nonclinical uses. The earliest study appeared in 2006, but over one third of the identified studies have been published in 2021 or later. The passage of time has seen an increased likelihood of HEMS AI studies focusing on nonclinical issues; for each year, the likelihood of a nonclinical focus had an odds ratio of 1.3. CONCLUSION: This scoping review provides overview and hypothesis-generating information regarding AI applications specific to HEMS. HEMS AI may be ultimately deployed in nonclinical arenas as much as or more than for clinical decision support. Future studies will inform future decisions as to how AI may improve HEMS systems design, asset deployment, and clinical care.

Natural Experiment Outcomes Studies in Rotor Wing Air Medical Transport: Systematic Review and Meta-Analysis of Before-and-After and Helicopter-Unavailable Publications From 1970 to 2022.

OBJECTIVE: Helicopter emergency medical services (HEMS) is widely used for prehospital and interfacility transport, but there is a paucity of HEMS outcomes data from studies using randomized controlled trial designs. In the absence of robust randomized controlled trial evidence, judgments regarding HEMS potential benefit must be informed by observational data. Within the study design set of observational analyses, the natural experiment (NE) is notable for its high potential methodologic quality; NE designs are occasionally denoted "quasi-experimental." The aim of this study is to examine all NE outcomes studies in the HEMS literature and to discern what lessons can be learned from these potentially high-quality observational data. METHODS: HEMS NE studies were identified during the development of a new HEMS Outcomes Assessment Research Database (HOARD). HOARD was constructed using a broad-ranging search of published and gray literature resources (eg, PubMed, Embase, and Google Scholar) that used variations of the terms "helicopter EMS," "air ambulance," and "air medical transport." Among the 221 studies ultimately included in HOARD, 16 NE publications describing 13 sets of observational data comprising myriad diagnostic groups were identified. Of these 16 HEMS NEs, 4 HEMS NE studies assessing trauma outcomes were used in a meta-analysis. A meta-analysis was also performed of 4 HEMS NE studies. RESULTS: Although the disparity of studies (in terms of both case mix and end points) precluded the generation of a pooled effect estimate of an adjusted mortality benefit of HEMs versus ground emergency medical services, HEMS was found to be associated with outcomes improvement in 8 of the 13 cohorts. CONCLUSION: The weight of the NE evidence supports a conclusion of some form of HEMS-mediated outcomes improvement in a variety of patient types. Meta-analysis of 4 HEMS NE studies assessing trauma outcomes generated a model with acceptable heterogeneity (I2 = 43%, Q test: P = .16), which significantly (P < .01) favored HEMS use with a pooled HEMS survival odd ratio estimate of 1.66 (95% confidence interval, 1.23-2.22).

A multicentre observational study to investigate feasibility of a direct oral penicillin challenge in de-labelling 'low risk' patients with penicillin allergy by non-allergy healthcare professionals (SPACE study): Implications for healthcare systems.

OBJECTIVE: The huge burden of inaccurate penicillin allergy labels (PALs) is an important driver of antimicrobial resistance. This is magnified by insufficient allergy specialists and lack of 'point-of-care' tests. We investigated the feasibility of non-allergy healthcare professionals (HCPs) delivering direct oral penicillin challenges (DPCs) for penicillin allergy de-labelling. METHODS: This prospective observational study was conducted in three hospitals in England across three settings (acute medical, pre-surgical and haematology-oncology). Patients with a PAL were screened and stratified as low risk/high risk. Low risk patients (non-immune mediated symptoms, benign rash, tolerated amoxicillin since and family history) underwent a DPC. RESULTS: N = 2257 PALs were screened, 1054 were eligible; 643 were approached, 373 declined, 270 consented and 259 risk stratified (low risk = 155; high risk = 104). One hundred and twenty-six low risk patients underwent DPC, 122 (96.8%) were de-labelled with no serious allergic reactions. Conversion rate from screening-to-consent was 12% [3.3% and 17.9% in acute and elective settings respectively; odds ratios for consent were 3.42 (p < 0.001) and 5.53 (p < 0.001) in haematology-oncology and pre-surgical setting respectively. Common reasons for failure to progress in the study included difficulty in reaching patients, clinical instability/medical reasons, lacking capacity to consent and psychological factors. INTERPRETATION: DPCs can be delivered by non-allergy HCPs. A high proportion of patients with PALs did not progress in the study pathway. Strategies to deliver DPC at optimal points of the care pathway are needed to enhance uptake. Elective settings offer greater opportunities than acute settings for DPC. The safety and simplicity of DPCs lends itself to adoption by healthcare systems beyond the UK, including in resource-limited settings.

Nation-Wide Variation in Presence of Legislation or Protocols for EMS Care of Operational Canines.

BACKGROUND & AIMS: Deployment of law enforcement operational canines (OpK9s) risks injuries to the animals. This study's aim was to assess the current status of states' OpK9 (veterinary Emergency Medical Services [VEMS]) laws and care protocols within the United States. METHODS: Cross-sectional standardized review of state laws/regulations and OpK9 VEMS treatment protocols was undertaken. For each state and for the District of Columbia (DC), the presence of OpK9 legislation and/or care protocols was ascertained. Information was obtained through governmental records and from stakeholders (eg, state EMS medical directors and state veterinary boards).The main endpoints were proportions of states with OpK9 laws and/or treatment protocols. Proportions are reported with 95% confidence intervals (CIs). Fisher's exact test (P <.05) assessed whether presence of an OpK9 law in a given jurisdiction was associated with presence of an OpK9 care protocol, and whether there was geographic variation (based on United States Census Bureau regions) in presence of OpK9 laws or protocols. RESULTS: Of 51 jurisdictions, 20 (39.2%) had OpK9 legislation and 23 (45.1%) had state-wide protocols for EMS treatment of OpK9s. There was no association (P = .991) between presence of legislation and presence of protocols. There was no association (P = .144) between presence of legislation and region: Northeast 66.7% (95% CI, 29.9-92.5%), Midwest 50.0% (95% CI, 21.1-78.9%), South 29.4% (95% CI, 10.3-56.0%), and West 23.1% (95% CI, 5.0-53.8%). There was significant (P = .001) regional variation in presence of state-wide OpK9 treatment protocols: Northeast 100.0% (95% CI, 66.4-100.0%), Midwest 16.7% (95% CI, 2.1-48.4%), South 47.1% (95% CI, 23.0-72.2%), and West 30.8% (95% CI, 9.1-61.4%). CONCLUSION: There is substantial disparity with regard to presence of OpK9 legal and/or clinical guidance. National collaborative guidelines development is advisable to optimize and standardize care of OpK9s. Additional attention should be paid to educational and training programs to best utilize the limited available training budgets.

Antinuclear antibody-associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus.

ABSTRACT: Autoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS'CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.

Racial and Ethnic Disparities in Receipt of General Anesthesia for Cesarean Delivery.

Importance: General anesthesia for cesarean delivery is associated with increased maternal morbidity, and Black and Hispanic pregnant patients have higher rates of general anesthesia use compared with their non-Hispanic White counterparts. It is unknown whether risk factors and indications for general anesthesia differ among patients of differing race and ethnicity. Objective: To evaluate differences in general anesthesia use for cesarean delivery and the indication for the general anesthetic by race and ethnicity. Design, Setting, and Participants: In this retrospective, cross-sectional, single-center study, electronic medical records for all 35 117 patients who underwent cesarean delivery at Northwestern Medicine's Prentice Women's Hospital from January 1, 2007, to March 2, 2018, were queried for maternal demographics, clinical characteristics, obstetric and anesthetic data, the indication for cesarean delivery, and the indication for general anesthesia when used. Data analysis occurred in August 2023. Exposure: Cesarean delivery. Main Outcomes and Measures: The rate of general anesthesia for cesarean delivery by race and ethnicity. Results: Of the 35 117 patients (median age, 33 years [IQR, 30-36 years]) who underwent cesarean delivery, 1147 (3.3%) received general anesthesia; the rates of general anesthesia were 2.5% for Asian patients (61 of 2422), 5.0% for Black patients (194 of 3895), 3.7% for Hispanic patients (197 of 5305), 2.8% for non-Hispanic White patients (542 of 19 479), and 3.8% (153 of 4016) for all other groups (including those who declined to provide race and ethnicity information) (P < .001). A total of 19 933 pregnant patients (56.8%) were in labor at the time of their cesarean delivery. Of those, 16 363 (82.1%) had neuraxial labor analgesia in situ. Among those who had an epidural catheter in situ, there were no racial or ethnic differences in the rates of general anesthesia use vs neuraxial analgesia use (Asian patients, 34 of 503 [6.8%] vs 1289 of 15 860 [8.1%]; Black patients, 78 of 503 [15.5%] vs 1925 of 15 860 [12.1%]; Hispanic patients, 80 of 503 [15.9%] vs 2415 of 15 860 [15.2%]; non-Hispanic White patients, 255 of 503 [50.7%] vs 8285 of 15 860 [52.2%]; and patients of other race or ethnicity, 56 of 503 [11.1%] vs 1946 of 15 860 [12.3%]; P = .16). Indications for cesarean delivery and for general anesthesia were not different when stratified by race and ethnicity. Conclusions and Relevance: Racial disparities in rates of general anesthesia continue to exist; however, this study suggests that, for laboring patients who had labor epidural catheters in situ, no disparity by race or ethnicity existed. Future studies should address whether disparities in care that occur prior to neuraxial catheter placement are associated with higher rates of general anesthesia among patients from ethnic and racial minority groups.

A software tool to support follow-up care in a French childhood cancer cohort: construction and feasibility.

BACKGROUND: Treatment summaries and a personalized survivorship care plans based on internationally approved, organ-specific follow-up care recommendations are essential in preserving the health and quality of life for cancer survivors. Cohorts made up of survivors of childhood cancer have made significant contributions to the understanding of early mortality, somatic late complications, and psychosocial outcomes among former patients. New treatment protocols are needed to enhance survival and reduce the potential risk and severity of late effects, and working with treatment databases is crucial in doing so. CONSTRUCTION AND CONTENT: In the GOCE (Grand Ouest Cancer de l'Enfant [Western Region Childhood Cancer]) network, in a participative approach, we developed the LOG-after medical tool, on which health data are registered and can be extracted for analysis. Its name emphasizes the tool's goal, referring to 'logiciel' (the French word for software) that focuses on the period "after" the acute phase. This tool is hosted on a certified health data server. Several interfaces have been developed that can be used depending on the user's profile. Here we present this innovative co-constructed tool that takes national aspects into account, including the results of the feasibility/satisfaction study and its perspective. UTILITY AND DISCUSSION: The database contains data relating to 2558 patients, with samples from 1702 of these (66.54%) being held in a tumor bank. The average year in which treatment started was 2015 (ranging from December 1967 to November 2022: 118 patients were treated before 2012 and registered retrospectively when seen in long-term follow-up consultations or for another cancer since November 2021). A short questionnaire was distributed to healthcare professionals using the tool (physicians and research associates or technicians, n = 14), of whom 11 answered and were all satisfied. Access to the patient interface is currently open to 124 former patients. This was initially offered to 30 former patients who were over 15 years old, affected by the disease within the last 5 years, and had agreed to test it. Their opinions were collected by their doctor by e-mail, telephone, or during a consultation in an open-ended question and a non-directive interview. All patients were satisfied with the tool, with interest in testing it in the long term. Some former patients found that the tool provided them with some ease of mind; one, for instance, commented: "I feel lighter. I allow myself to forget. I know I will get a notification when the time comes." CONCLUSIONS: Freely available to all users, LOG-after: (1) provides help with determining personalized survivorship care plans for follow-up; (2) builds links with general practitioners; (3) empowers the patient; and (4) enables health data to be exported for analysis. Database URL for presentation: https://youtu.be/2Ga64iausJE.

Long-term neurotoxicity among childhood acute lymphoblastic leukaemia survivors enrolled between 1971 and 1998 in EORTC Children Leukemia Group studies.

Survival after childhood acute lymphoblastic leukemia (ALL) has increased over the last 40 years with an overall survival above 90%. Survivors may experience neurological late effects secondary to chemotherapy and radiotherapy. This observational retrospective study evaluated the cumulative incidence of neurological late effects among 890 childhood ALL survivors treated in EORTC CLG trials (58741, 58831/2 and 58881) between 1971 and 1998. Median follow-up was 19 years and interquartile range of the follow-up was 15-22 years. At 20 years from the end of treatment, approximately 66% of patients from the 58741 trial (accrual time: 1971-1978) and approximately 15% from the more recent trials had cognitive disturbance grade 1 or higher. Cumulative incidences at 20 years from treatment end of seizures, stroke and leukoencephalopathy were respectively 45%, 16% and 62% in study 58741, 13%, 2% and 5% in study 58831/2, and 8%, 2% and 3% in study 58881. Patients who were 10-17 years of age at diagnosis had a higher incidence of stroke and leukoencephalopathy as compared to those less than 6 years of age. Noteworthy, all neurological late effects continued to occur beyond 5 years after end of treatment. This retrospective study highlights the frequency of neurological late effects in survivors of childhood ALL. With the increase of the overall survival of ALL patients, the role and potential benefit of longitudinal neurological screening should be evaluated in further studies as these neurological late effects become an important public health challenge. This study is part of the larger EORTC CLG 58 Late Adverse Effects (LAE) study (ClinicalTrials.gov Identifier NCT01298388, date of registration February 16, 2011).

Added value of molecular karyotype in childhood acute lymphoblastic leukemia.

Background: Thanks to an improved therapeutic regimen in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), 5 year-overall survival now exceeds 90%. Unfortunately, the 25% of children who relapse have an initial poor prognosis, potentially driven by pre-existing or emerging molecular anomalies. The latter are initially and essentially identified by cytogenetics. However, some subtle alterations are not visible through karyotyping. Methods: Single nucleotide polymorphisms (SNP) array is an alternative way of chromosomal analysis allowing for a more in-depth evaluation of chromosomal modifications such as the assessment of copy number alterations (CNA) and loss of heterozygosity (LOH). This method was applied here in retrospective diagnosis/relapse paired samples from seven children with BCP-ALL and in a prospective cohort of 38 newly diagnosed childhood cases. Results: In the matched study, compared to the initial karyotype, SNP array analysis reclassified two patients as poor prognosis cases. Modulation during relapse was seen for 4 CNA and 0.9 LOH. In the prospective study, SNP reclassified the 10 patients with intermediate karyotype as 7 good prognosis and 3 poor prognosis. Ultimately, in all the children tested, SNP array allowed to identify additional anomalies compared to conventional karyotype, refine its prognostic value and identify some druggable anomalies that could be used for precision medicine. Overall, the anomalies detected could be segregated in four groups respectively involved in B-cell development, cell proliferation, transcription and molecular pathways. Conclusion: SNP therefore appears to be a method of choice in the integrated diagnosis of BCP ALL, especially for patients initially classified as intermediate prognosis. This complementary method of both cytogenetics and high throughput sequencing allows to obtain further classified information and can be useful in case of failure of these techniques.

A Case Report of Percutaneous Right Ventricular Assist Device Utilization After Cesarean Delivery in a Patient With Severe Pulmonary Arterial Hypertension.

Physiologic changes of pregnancy are poorly tolerated in patients with pulmonary arterial hypertension (PAH), and peripartum maternal mortality is high. We present a case of a 31-year-old G3P0020 patient at 35 weeks' gestation with severe World Health Organization group I PAH who underwent cesarean delivery followed by percutaneous right ventricular assist device placement. Risks and benefits of the mode of delivery, neuraxial versus general anesthesia, and mechanical circulatory support are reviewed.

Perturbations in indices of oxidative stress, oxidative DNA damage and lung function in chronic exposure to wood dust in Southern Nigeria.

OBJECTIVES: Oxidative stress (OS) and oxidative DNA damage accruing from chronic exposure to wood dust have been implicated in the development of chronic lung conditions among woodworkers. Indices of OS, inflammation, oxidative DNA damage and lung function in relation to duration of exposure to wood dust were assessed in woodworkers to determine their possible utility as risk evaluation indices for chronic lung conditions. METHODS: Ninety participants comprising 30 active woodworkers, 30 passive woodworkers, and 30 controls were enrolled into this cross-sectional study. The total plasma peroxides, total antioxidant capacity (TAC), oxidative stress index (OSI), malondialdehyde (MDA), reduced glutathione, nitric oxide, high sensitivity C-reactive protein (hs-CRP), 8-hydroxy-2'-deoxyguanosine (8-OHdG) and peak expiratory flow rate (PEFR) were determined in all participants. RESULTS: Woodworkers had lower PEFR, TAC, and higher malondialdehyde, OSI, hs-CRP, and 8-OHdG compared to controls (p < 0.05). Active woodworkers had higher malondialdehyde, 8-OHdG, and hs-CRP compared to passive woodworkers (p < 0.05). Increasing duration of exposure to wood dust is associated with higher malondialdehyde, hs-CRP, and 8-OHdG in active woodworkers (p < 0.05) and higher 8-OHdG and hs-CRP in passive woodworkers (p < 0.05). Negative correlation was observed between hs-CRP and TAC (r=-0.367, p = 0.048) in active workers. CONCLUSION: The association of exposure to wood dust with elevated indices of inflammation, OS, lipid peroxidation, oxidative DNA damage, and reduction in antioxidants and peak expiratory flow rate; and the concomitant increase in oxidative DNA damage and inflammation with increasing duration of exposure suggest that these indices may be useful in predicting woodworkers at risk of development of chronic lung conditions.

Molecular and clinicopathologic characterization of pediatric histiocytoses.

The spectrum of somatic mutations in pediatric histiocytoses and their clinical implications are not fully characterized, especially for non-Langerhans cell histiocytosis (-LCH) subtypes. A cohort of 415 children with histiocytosis from the French histiocytosis registry was reviewed and analyzed for BRAFV600E . Most BRAFWT samples were analyzed by next-generation sequencing (NGS) with a custom panel of genes for histiocytosis and myeloid neoplasia. Of 415 case samples, there were 366 LCH, 1 Erdheim-Chester disease, 21 Rosai-Dorfman disease (RDD), 21 juvenile xanthogranuloma (JXG, mostly with severe presentation), and 6 malignant histiocytosis (MH). BRAFV600E was the most common mutation found in LCH (50.3%, n = 184). Among 105 non-BRAFV600E -mutated LCH case samples, NGS revealed mutations as follows: MAP2K1 (n = 44), BRAF exon 12 deletions (n = 26), and duplications (n = 8), other BRAF V600 codon mutation (n = 4), and non-MAP-kinase pathway genes (n = 5). Wild-type sequences were identified in 17.1% of samples. BRAFV600E was the only variant significantly correlated with critical presentations: organ-risk involvement and neurodegeneration. MAP-kinase pathway mutations were identified in seven RDD (mostly MAP2K1) and three JXG samples, but most samples were wild-type on NGS. Finally, two MH samples had KRAS mutations, and one had a novel BRAFG469R mutation. Rarely, we identified mutations unrelated to MAP-kinase pathway genes. In conclusion, we characterized the mutational spectrum of childhood LCH and clinical correlations of variants and subtypes. Variants responsible for JXG and RDD were not elucidated in more than half of the cases, calling for other sequencing approaches.