Case report: Slipped capital femoral epiphysis: a rare adverse event associated with FGFR tyrosine kinase inhibitor therapy in a child.

We report a case of slipped capital femoral epiphysis (SCFE), an on target skeletal toxicity of a pan-FGFR TKI inhibitor, erdafitinib. A 13-year-old boy was diagnosed to have an optic pathway/hypothalamic glioma with signs of increased intracranial pressure and obstructive hydrocephalus requiring placement of ventriculo-peritoneal (VP) shunt. Sequencing of the tumor showed FGFR1-tyrosine kinase domain internal tandem duplication (FGFR1-KD-ITD). He developed hypothalamic obesity with rapid weight gain and BMI >30. At 12 weeks of treatment with erdafitinib, he developed persistent knee pain. X-ray of the right hip showed SCFE. Erdafitinib was discontinued, and he underwent surgical pinning of the right hip. MRI at discontinuation of erdafitinib showed a 30% decrease in the size of the tumor, which has remained stable at 6 months follow-up. Our experience and literature review suggest that pediatric patients who are treated with pan-FGFR TKIs should be regularly monitored for skeletal side effects.

Plain film measurement error in acute displaced midshaft clavicle fractures.

BACKGROUND: Clavicle fractures are common and optimal treatment remains controversial. Recent literature suggests operative fixation of acute displaced mid-shaft clavicle fractures (DMCFs) shortened more than 2 cm improves outcomes. We aimed to identify correlation between plain film and computed tomography (CT) measurement of displacement and the inter- and intraobserver reliability of repeated radiographic measurements. METHODS: We obtained radiographs and CT scans of patients with acute DMCFs. Three orthopedic staff and 3 residents measured radiographic displacement at time zero and 2 weeks later. The CT measurements identified absolute shortening in 3 dimensions (by subtracting the length of the fractured from the intact clavicle). We then compared shortening measured on radiographs and shortening measured in 3 dimensions on CT. Interobserver and intraobserver reliability were calculated. RESULTS: We reviewed the fractures of 22 patients. Bland-Altman repeatability coefficient calculations indicated that radiograph and CT measurements of shortening could not be correlated owing to an unacceptable amount of measurement error (6 cm). Interobserver reliability for plain radiograph measurements was excellent (Cronbach α = 0.90). Likewise, intraobserver reliabilities for plain radiograph measurements as calculated with paired t tests indicated excellent correlation (p > 0.05 in all but 1 observer [p = 0.04]). CONCLUSION: To establish shortening as an indication for DMCF fixation, reliable measurement tools are required. The low correlation between plain film and CT measurements we observed suggests further research is necessary to establish what imaging modality reliably predicts shortening. Our results indicate weak correlation between radiograph and CT measurement of acute DMCF shortening.

CONTEXTE: Les fractures de la clavicule sont fréquentes, et le choix du traitement optimal ne fait pas l'unanimité. Selon la littérature récente, la fixation chirurgicale des fractures du tiers médial déplacées (FTMD) aiguës raccourcies de plus de 2 cm donnerait de meilleurs résultats. Nous avons voulu établir une corrélation entre la mesure du déplacement obtenue par radiographie simple et par tomodensitométrie (TDM) et la fiabilité inter- et intra-observateur des mesures radiographiques répétées. MÉTHODES: Nous avons obtenu les radiographies et les TDM de patients ayant subi une FTMD aiguë. Trois orthopédistes et 3 résidents ont mesuré le déplacement radiographique au temps zéro et 2 semaines plus tard. Les mesures par TDM ont permis d'identifier un raccourcissement absolu en 3 dimensions (en soustrayant de la longueur de la clavicule intacte celle de la clavicule brisée). Nous avons ensuite comparé le raccourcissement mesuré par radiographie au raccourcissement en 3 dimensions mesuré par TDM. La fiabilité inter- et intra-observateur a ensuite été calculée. RÉSULTATS: Nous avons ainsi analysé les fractures de 22 patients. Les calculs du coefficient de répétabilité de Bland et Altman ont indiqué qu'il était impossible d'établir des corrélations entre les mesures obtenues par radiographie et par TDM compte tenu de l'ampleur inacceptable de l'erreur de mesure (6 cm). La fiabilité inter-observateur a été excellente pour les mesures radiographiques (coefficient α de Cronbach = 0,90). De même, la fiabilité intra-observateur pour les mesures radiographiques calculée par test t pour échantillons appariés a indiqué une excellente corrélation (p > 0,05 chez tous les observateurs, sauf 1 [p = 0,04]). CONCLUSION: Pour que le raccourcissement devienne une indication de la FTMD, il faut disposer d'outils de mesure fiables. La faible corrélation que nous avons observée entre les mesures obtenues par radiographie et par TDM montre qu'il faut approfondir la recherche afin de déterminer quelle modalité permet de prédire de manière fiable le raccourcissement. Nos résultats démontrent une faible corrélation entre les mesures du raccourcissement obtenues par radiographie et par TDM dans la FTMD aiguë.

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction.

BACKGROUND: Immune modulation by the Celacade system (Vasogen Inc, Canada) decreases mortality and hospitalization in human heart failure. OBJECTIVES: To study the effects of Celacade in rats on acute cytokine expression after coronary artery ligation, cardiac dimensions following myocardial infarction (MI), and systolic and diastolic function of cardiac muscle in MI. METHODS: Celacade treatment was administered 14 days before coronary artery ligation and monthly after the surgery. Cytokine expression in cardiac tissue was measured on days 1 and 7 by ELISA in sham rats and in rats with MI (with or without Celacade treatment). Echocardiograms were obtained serially for 16 weeks. Force and sarcomere length (SL) were measured by strain gauge and laser diffraction in isolated right ventricle trabeculas at 16 weeks. The inotropic effect of pacing on force was quantified as F5 Hz/0.5 Hz. Diastolic dysfunction was quantified as the root mean square of spontaneous SL fluctuations. RESULTS: Celacade inhibited transforming growth factor beta-1 production in the infarct area on day 7 (191.6+/-22.6 pg/mg versus 275.4+/-30.1 pg/mg; P<0.05), but did not attenuate cardiac dilation in MI. Celacade restored positive inotropism of pacing in MI (F5 Hz/0.5 Hz in Celacade, 219.1+/-46.7%; MI, 148.1+/-27.1% [P<0.05 compared with 211.4+/-37.9% in sham]). Celacade reduced diastolic dysfunction in MI (root mean square of spontaneous SL fluctuations: 121+/-15% and 143+/-19% with Celacade versus 184+/-19% and 190+/-26% without Celacade at 26 degrees C and 36 degrees C, respectively) compared with sham (100%; P<0.05). CONCLUSIONS: Celacade reduces the increase of transforming growth factor beta-1 expression during the acute stage of MI in rats, but does not prevent chronic cardiac dilation. Celacade restores the positive inotropic effect of increased pacing rate in trabeculas from rat right ventricles with large MIs and reduces diastolic dysfunction.