The erector spinae plane block vs. usual care for treatment of mechanical back pain in the emergency department: a pilot study.

BACKGROUND: The ultrasound-guided erector spinae plane block (ESPB), traditionally utilized for thoracic regional pain control, has been reported as an effective analgesic option for mechanical back pain, renal colic, and rib fractures in the emergency department (ED). This pilot study aims to compare the effectiveness of the ESPB to usual analgesic treatment for patients presenting to the ED with mechanical back pain. METHODS: A prospective, single-blind randomized controlled trial was conducted at a Canadian community hospital from March 2020 to December 2022. Adult patients presenting to the ED with mechanical back pain of at least 7 out of 10 on the Numeric Pain Rating Scale (NPRS) were randomized to receive either the ESPB or usual care. The primary outcome was the difference in NPRS score reduction at ED discharge. Secondary outcomes included ED length of stay, ED opiate use, follow-up NPRS and Brief Pain Inventory (BPI) scores, back pain-related return ED visits, and ongoing opiate use. RESULTS: A total of 30 patients were enrolled, with 19 randomized to the ESPB cohort and 11 to the usual care cohort. The mean NPRS reduction at ED discharge was significantly higher in the ESPB group compared to the usual care group (5.4 vs. 2.2), with a difference of 3.2 (95% confidence interval 1.4-5.1). ED opiate use was lower in the ESPB group. The ESPB also resulted in a significant reduction in ED length of stay (160 min vs. 235 min). There were no reported adverse effects related to the research interventions. CONCLUSION: This pilot study suggests that the ESPB may be an effective opioid-sparing analgesic option for patients presenting to the ED with mechanical back pain. GOV IDENTIFIER: NCT05982483.

RéSUMé: CONTEXTE: Le bloc raboteux spina érectile guidé par ultrasons (ESPB), traditionnellement utilisé pour le contrôle de la douleur régionale thoracique, a été signalé comme une option analgésique efficace pour les maux de dos mécaniques, les coliques rénales et les fractures des côtes au service des urgences (ED). Cette étude pilote vise à comparer l'efficacité de l'ESPB au traitement analgésique habituel pour les patients présentant à l'urgence des douleurs dorsales mécaniques. MéTHODES: Un essai contrôlé randomisé prospectif en aveugle a été mené dans un hôpital communautaire canadien de mars 2020 à décembre 2022. Les patients adultes se présentant à l'urgence avec une douleur dorsale mécanique d'au moins 7 sur 10 sur l'échelle numérique d'évaluation de la douleur (NPRS) ont été randomisés pour recevoir soit la ESPB ou les soins habituels. Le critère de jugement principal était la différence dans la réduction du score NPRS à la sortie de l'urgence. Les critères de jugement secondaires comprenaient la durée du séjour à l'urgence, l'utilisation d'opiacés à l'urgence, les scores de suivi à l'INRP et au Brief Pain Inventory (BPI), les visites de retour à l'urgence liées à la douleur dorsale et l'utilisation continue d'opiacés. RéSULTATS: Au total, 30 patients ont été recrutés, dont 19 randomisés dans la cohorte de la DGPSE et 11 dans la cohorte de soins habituels. La réduction moyenne du NPRS à la sortie de l'urgence était significativement plus élevée dans le groupe ESPB que dans le groupe de soins habituels (5,4 vs. 2,2), avec une différence de 3,2 (intervalle de confiance à 95 % 1,4-5,1). La consommation d'opiacés aux urgences était plus faible dans le groupe ESPB. La ESPB a également entraîné une réduction significative de la durée du séjour aux urgences (160 min contre 235 min). Aucun effet indésirable lié aux interventions de recherche n'a été signalé. CONCLUSION: Cette étude pilote suggère que l'ESPB peut être une option analgésique efficace épargnant les opioïdes pour les patients se présentant à l'urgence avec des douleurs dorsales mécaniques.

Rapid, economical diagnostic classification of ATRT molecular subgroup using NanoString nCounter platform.

Background: Despite genomic simplicity, recent studies have reported at least 3 major atypical teratoid rhabdoid tumor (ATRT) subgroups with distinct molecular and clinical features. Reliable ATRT subgrouping in clinical settings remains challenging due to a lack of suitable biological markers, sample rarity, and the relatively high cost of conventional subgrouping methods. This study aimed to develop a reliable ATRT molecular stratification method to implement in clinical settings. Methods: We have developed an ATRT subgroup predictor assay using a custom genes panel for the NanoString nCounter System and a flexible machine learning classifier package. Seventy-one ATRT primary tumors with matching gene expression array and NanoString data were used to construct a multi-algorithms ensemble classifier. Additional validation was performed using an independent gene expression array against the independently generated dataset. We also analyzed 11 extra-cranial rhabdoid tumors with our classifier and compared our approach against DNA methylation classification to evaluate the result consistency with existing methods. Results: We have demonstrated that our novel ensemble classifier has an overall average of 93.6% accuracy in the validation dataset, and a striking 98.9% accuracy was achieved with the high-prediction score samples. Using our classifier, all analyzed extra-cranial rhabdoid tumors are classified as MYC subgroups. Compared with the DNA methylation classification, the results show high agreement, with 84.5% concordance and up to 95.8% concordance for high-confidence predictions. Conclusions: Here we present a rapid, cost-effective, and accurate ATRT subgrouping assay applicable for clinical use.

A kinome drug screen identifies multi-TKI synergies and ERBB2 signaling as a therapeutic vulnerability in MYC/TYR subgroup ATRTs.

BACKGROUND: Atypical Teratoid Rhabdoid Tumor (ATRT) is a rare, devastating, and largely incurable pediatric brain tumor. Although recent studies have uncovered three molecular subgroups of ATRTs with distinct disease patterns, and signaling features, the therapeutic profiles of ATRT subgroups remain incompletely elucidated. METHODS: We examined the effect of 465 kinase inhibitors on a panel of ATRT subgroup-specific cell lines. We then applied multi-omics analyses to investigate the underlying molecular mechanism of kinase inhibitor efficacy in ATRT subgroups. RESULTS: We observed that ATRT cell lines are broadly sensitive to inhibitors of the PI3K and MAPK signaling pathways, as well as CDKs, AURKA/B kinases, and PLK1. We identified two classes of multi-kinase inhibitors (MKIs) predominantly targeting receptors tyrosine kinase (RTKs) including PDGFR and EGFR/ERBB2 in MYC/TYR ATRT cells. The PDGFRB inhibitor, Dasatinib, synergistically affected MYC/TYR ATRT cell growth when combined with broad-acting PI3K and MAPK pathway inhibitors, including Rapamycin and Trametinib. We observed that MYC/TYR ATRT cells were also distinctly sensitive to various inhibitors of ERBB2 signaling. Transcriptional, H3K27Ac ChIPSeq, ATACSeq, and HiChIP analyses of primary MYC/TYR ATRTs revealed ERBB2 expression which correlated with differential methylation and activation of a distinct enhancer element by DNA looping. Significantly, we show the brain penetrant EGFR/ERBB2 inhibitor, Afatinib, specifically inhibited in vitro and in vivo growth of MYC/TYR ATRT cells. CONCLUSIONS: Taken together our studies suggest combined treatments with PDGFR and ERBB2-directed TKIs with inhibitors of the PI3K and MAPK pathways as an important new therapeutic strategy for the MYC/TYR subgroup of ATRTs.