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The cornerstone treatment for immune-mediated thrombotic thrombocytopenic purpura (iTTP) in children is a combination of therapeutic plasma exchange (TPE), corticosteroids, and rituximab. Caplacizumab is an anti-von Willebrand factor (VWF) NANOBODY molecule approved as a frontline therapy of iTTP for adults and children aged ≥12 years. Using caplacizumab in children aged <12 years remains a gray area based on recommendations but with no marketing authorization. We report the first case of a pediatric patient with iTTP successfully treated with a caplacizumab dose adjustment of 5 mg daily based on ADAMTS13 activity. We also review all published cases of iTTP in children aged <12 years treated with caplacizumab. This is a 7-year-old girl with clinical thrombotic microangiopathy, in the absence of diarrhea and kidney injury. With a French score of 2 and a PLASMIC score of 7 (high risk), the diagnosis of TTP was suspected and later confirmed by severely low ADAMTS13 activity (<5%). Immune-mediated TTP was distinguished from the congenital one due to the presence of a functional ADAMTS13 inhibitor. Daily TPE and intravenous corticosteroids were started on day 0 (D0). Rituximab was added on D4, and due to refractoriness under daily TPE, we considered off-label administration of caplacizumab from D12. A clinical answer, with a significant increase in the platelet count, was observed within 48 h. A complete ADAMTS13 recovery was reached on D62. No major adverse events were observed during the treatment. She was discharged from the hospital over 3 months ago with a platelet count still within normal ranges. In the literature, we identified a total of four case reports describing five iTTP patients aged <12 years treated with caplacizumab, with a 100% success and tolerability rate. These published data attest to the efficacy and safety of the systematic use of caplacizumab and rituximab as frontline therapy in pediatric iTTP under 12 years of age. Therefore, prospective data are needed to support commercial authorization of caplacizumab in this subpopulation. Close monitoring of ADAMTS13 activity is particularly of interest among children to limit the number of caplacizumab injections., Competing Interests: Caplacizumab treatment was financed by Sanofi. JK is a member of the advisory board of Takeda, a member of the Takeda group of companies, for the development of recombinant ADAMTS13, and of Ablynx, now part of Sanofi for the development of caplacizumab, and has received lecture fees from Takeda and Sanofi. All honoraria are paid to her employer, Insel Gruppe AG, Bern, Switzerland. PC is a member of Sanofi's advisory board and has received honoraria for participating in symposia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Chavaz, Cimasoni, Kremer Hovinga, Coppo and Ansari.)

In this single-center study of 61 allogeneic hematopoietic cell transplant (HCT) recipients receiving letermovir primary cytomegalovirus (CMV) prophylaxis for the first 100 days, we report 23% incidence of clinically significant CMV infection during the first 100 days after letermovir discontinuation, predominately in haploidentical HCT recipients, without any associations with CMV-DNAemia under letermovir., Competing Interests: Potential conflicts of interest. L.C., L.R., S.M.-L., A.-C.M., F.G., S.M., and C.v.D. report no conflicts of interest. Y.C. has received consulting fees from MSD, Novartis, Incyte, BMS, Pfizer, AbbVie, Roche, Jazz, Gilead, Amgen, Astra-Zeneca, and Servier; travel support from MSD, Roche, Gilead, Amgen, Incyte, AbbVie, Janssen, Astra-Zeneca, and Jazz. D.N. has received research support from MSD and Pfizer and consulting fees from MSD, Pfizer, Basilea, and Gilead. All other authors report no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Object: Preoperative image-based neuronavigation-assisted endoscopy during intracranial procedures is gaining great interest. This study aimed to analyze the precision of navigation-assisted endoscopy according to the navigation setup, the type of optic and its working angulation., Methods: A custom-made box with four screws was referenced. The navigation-assisted endoscope was aligned on the screws (targets). The precision on the navigation screen was defined as the virtual distance-to-target between the tip of the endoscope and the center of the screws. Three modifiers were assessed: (1) the distance D between the box and the reference array (CLOSE 13 cm - MIDDLE 30 cm - FAR 53 cm), (2) the distance between the tip of the endoscope and the navigation array on the endoscope (close 5 cm - middle 10 cm - far 20 cm), (3) the working angulation of the endoscope (0°-endoscope and 30°-endoscope angled at 90° and 45° with the box)., Results: The median precision was 1.3 mm (Q1: 1.1; Q3: 1.7) with the best setting CLOSE/close. The best setting in surgical condition (CLOSE/far) showed a distance-to-target of 2.3 mm (Q1: 1.9; Q3: 2.5). The distance D was correlated to the precision (Spearman rho = 0.82), but not the distance d (Spearman rho = 0.04). The type of optic and its angulation with the box were also correlated to the precision (Spearman rho =  - 0.37). The best setting was the use of a 30°-endoscope angled at 45° (1.4 mm (Q1: 1.0; Q3: 1.9))., Conclusion: Navigated-assisted endoscopy is feasible and offers a good precision. The navigation setup should be optimized, reducing the risk of inadvertent perifocal damage., (© 2022. The Author(s).)

Competing Interests: L’auteure n’a déclaré aucun conflit d’intérêts en relation avec cet article.

Objective: Intracranial minimally invasive procedures imply working in a restricted surgical corridor surrounded by critical structures, such as vessels and cranial nerves. Any damage to them may affect patient outcome. Neuronavigation systems may reduce the risk of such complications. In this study, the authors sought to compare standard neuronavigation (NV) and augmented reality (AR)-guided navigation with respect to the integrity of the perifocal structures during a neurosurgical approach using a novel model imitating intracranial vessels., Methods: A custom-made box, containing crisscrossing hard metal wires, a hidden nail at its bottom, and a wooden top, was scanned, fused, and referenced for the purpose of the study. The metal wires and an aneurysm clip applier were connected to a controller, which counted the number of contacts between them. Twenty-three naive participants were asked to 1) use NV to define an optimal entry point on the top, perform the smallest craniotomy possible on the wooden top, and to use a surgical microscope when placing a clip on the nail without touching the metal wires; and 2) use AR to preoperatively define an ideal trajectory, navigate the surgical microscope, and then perform the same task. The primary outcome was the number of contacts made between the metal wires and the clip applier. Secondary outcomes were craniotomy size, and trust in NV and AR to help avoid touching the metal wires, as assessed by a 9-level Likert scale., Results: The median number of contacts tended to be lower with the use of AR than with NV (AR, median 1 [Q1: 1, Q3: 2]; NV, median 3 [Q1: 1, Q3: 6]; p = 0.074). The size of the target-oriented craniotomy was significantly lower with the use of AR compared with NV (AR, median 4.91 cm2 [Q1: 4.71 cm2, Q3: 7.55 cm2]; and NV, median 9.62 cm2 [Q1: 7.07 cm2; Q3: 13.85 cm2]). Participants had more trust in AR than in NV (the differences posttest minus pretest were mean 0.9 [SD 1.2] and mean -0.3 [SD 0.2], respectively; p < 0.05)., Conclusions: The results of this study show a trend favoring the use of AR over NV with respect to reducing contact between a clip applier and the perifocal structures during a simulated clipping of an intracranial aneurysm. Target-guided craniotomies were smaller with the use of AR. AR may be used not only to localize surgical targets but also to prevent complications associated with damage to structures encountered during the surgical approach.

Objective: Augmented reality (AR) in cranial surgery allows direct projection of preregistered overlaid images in real time on the microscope surgical field. In this study, the authors aimed to compare the precision of AR-assisted navigation and standard pointer-based neuronavigation (NV) by using a 3D-printed skull in surgical conditions., Methods: A commercial standardized 3D-printed skull was scanned, fused, and referenced with an MR image and a CT scan of a patient with a 2 × 2-mm right frontal sinus defect. The defect was identified, registered, and integrated into NV. The target was physically marked on the 3D-printed skull replicating the right frontal sinus defect. Twenty-six subjects participated, 25 of whom had no prior NV or AR experience and 1 with little AR experience. The subjects were briefly trained in how to use NV, AR, and AR recalibration tools. Participants were asked to do the following: 1) "target the center of the defect in the 3D-printed skull with a navigation pointer, assisted only by NV orientation," and 2) "use the surgical microscope and AR to focus on the center of the projected object" under conventional surgical conditions. For the AR task, the number of recalibrations was recorded. Confidence regarding NV and AR precision were assessed prior to and after the experiment by using a 9-level Likert scale., Results: The median distance to target was statistically lower for AR than for NV (1 mm [Q1: 1 mm, Q3: 2 mm] vs 3 mm [Q1: 2 mm, Q3: 4 mm] [p < 0.001]). In the AR task, the median number of recalibrations was 4 (Q1: 4, Q3: 4.75). The number of recalibrations was significantly correlated with the precision (Spearman rho: -0.71, p < 0.05). The trust assessment after performing the experiment scored a median of 8 for AR and 5.5 for NV (p < 0.01)., Conclusions: This study shows for the first time the superiority of AR over NV in terms of precision. AR is easy to use. The number of recalibrations performed using reference structures increases the precision of the navigation. The confidence regarding precision increases with experience.