Citations

Abstract Epilepsy neuroimaging assessment requires exceptional anatomic detail, physiologic and metabolic information. Magnetic resonance (MR) protocols are often time-consuming necessitating sedation and positron emission tomography (PET)/computed tomography (CT) comes with a significant radiation dose. Hybrid PET/MRI protocols allow for exquisite assessment of brain anatomy and structural abnormalities, in addition to metabolic information in a single, convenient imaging session, which limits radiation dose, sedation time, and sedation events. Brain PET/MRI has proven especially useful for accurate localization of epileptogenic zones in pediatric seizure cases, providing critical additional information and guiding surgical decision making in medically refractory cases. Accurate localization of seizure focus is necessary to limit the extent of the surgical resection, preserve healthy brain tissue, and achieve seizure control. This review provides a systematic overview with illustrative examples demonstrating the applications and diagnostic utility of PET/MRI in pediatric epilepsy.

Platelet-rich plasma (PRP) is a revolutionary treatment that harnesses the regenerative power of the body's own platelets to promote healing and tissue regeneration. While PRP therapy has emerged as a promising option for augmenting biologic healing in the shoulder, the complexity of shoulder disorders makes it difficult to draw definitive conclusions about the efficacy of PRP across different conditions and stages of disease. Our comprehensive review of twenty-four studies highlights the current state of PRP therapy in shoulder pathologies, revealing a wide variety of number of patients, control groups and results. Despite these challenges, the regenerative potential of PRP therapy is moderate in some conditions, with numerous studies demonstrating the positive effects. In conclusion, the authors of this study recommend the use of PRP therapy for adhesive capsulitis and rotator cuff repair of medium to large tears. However, they do not recommend the use of PRP for subacromial impingement or rotator cuff tears. It is up to the clinician's discretion to decide whether PRP therapy is appropriate for individual cases. However, there is still insufficient evidence to support the inclusion of PRP therapy in treatment protocols for other shoulder disorders. Therefore, further research is needed to fully explore the potential of PRP therapy in the treatment of various shoulder conditions.

Objective Perianal Crohn’s disease (pCD) occurs in up to 40% of patients with CD and is associated with poor quality of life, limited treatment responses and poorly understood aetiology. We performed a genetic association study comparing CD subjects with and without perianal disease and subsequently performed functional follow-up studies for a pCD associated SNP in Complement Factor B ( CFB ). Design Immunochip-based meta-analysis on 4056 pCD and 11 088 patients with CD from three independent cohorts was performed. Serological and clinical variables were analysed by regression analyses. Risk allele of rs4151651 was introduced into human CFB plasmid by site-directed mutagenesis. Binding of recombinant G252 or S252 CFB to C3b and its cleavage was determined in cell-free assays. Macrophage phagocytosis in presence of recombinant CFB or serum from CFB risk, or protective CD or healthy subjects was assessed by flow cytometry. Results Perianal complications were associated with colonic involvement, OmpC and ASCA serology, and serology quartile sum score. We identified a genetic association for pCD (rs4151651), a non-synonymous SNP (G252S) in CFB , in all three cohorts. Recombinant S252 CFB had reduced binding to C3b, its cleavage was impaired, and complement-driven phagocytosis and cytokine secretion were reduced compared with G252 CFB. Serine 252 generates a de novo glycosylation site in CFB. Serum from homozygous risk patients displayed significantly decreased macrophage phagocytosis compared with non-risk serum. Conclusion pCD-associated rs4151651 in CFB is a loss-of-function mutation that impairs its cleavage, activation of alternative complement pathway, and pathogen phagocytosis thus implicating the alternative complement pathway and CFB in pCD aetiology.

Abstract Background: Head and Neck (HNSCC) and Ovarian cancer (OC) are two indications for which immunotherapy had limited impact so far. Current treatments achieve high rates of initial success through surgery and adjuvant chemo/radiotherapy, but patients (pts) remain at high risk of relapse in both indications. Immune stimulation using a vaccine is a promising strategy to a clinically meaningful improvement. Herein we report phase I data of TG4050, a vaccine engineered to carry a pt tailored antigen payload, in pts with HNSCC (NCT04183166) or OC (NCT03839524). Methods: Tumor specific variants are identified using next generation sequencing of tumor and normal samples whereby immune relevant mutations are predicted using a machine learning algorithm factoring in parameters known to affect immunogenicity including MHC binding, level of expression, prevalence across clones, and antigen processing. DNA sequences of the mutations of interest, typically 30 per pt, are cloned in a viral vector (Modified Vaccinia Virus Ankara). Following curative intent treatment, HNSCC pts in complete remission were randomized to an immediate vaccination arm to receive weekly doses of TG4050 for 6 weeks followed by a maintenance period of one dose every 3 weeks for up to 20 doses or to a delayed vaccination arm where the same vaccination regimen is initiated at relapse. OC pts received the vaccine upon onset of signs of relapse. PBMC were collected at Baseline and after 6 doses of vaccine. Primary endpoint was vaccine safety and secondary endpoints included feasibility, immunogenicity. Results: 18 pts received TG4050 (5 OC and 13 HNSCC) treatment with no related grade ≥ 3 adverse events. Tumor mutational burden (TMB) was on average 3.00±0.98 and 2.43±0.69 mutations per megabase for HNSCC and OC respectively. Despite this low TMB, all pts had sufficient cancer specific neoantigens to design a vaccine. Ex-vivo ELISPOT was completed for 7 pts at the time of submission. A mean of 44% of selected mutations were associated with a reactive T cell responses either spontaneously or after TG4050 stimulation ranging from 6 to 22 mutations per pt. Vaccination induced a stimulation of T cell response in all tested pts on an average of 10 targeted mutations, induction of de novo responses was seen in all 7 tested pts and amplification of pre-existing response in 6/7 pts. None of the evaluable HNSCC pts receiving TG4050 immediately after first line treatment had relapse after a median follow-up of 7 months while 2 pts had relapse in the delayed vaccination arm. Furthermore, in OC pts treated at early relapse, TG4050 has normalized disease markers (ctDNA and/or CA-125) for 2/4 pts with stable disease for 9 and 11 months. Conclusion: TG4050 treatment is feasible and immunogenic in pts with low to moderate TMB. It is effective in inducing T cell responses and first signs of antitumor activity are encouraging for the continuation of development. Citation Format: Ana Lalanne, Camille Jamet, Christian H. Ottensmeier, Jean-Pierre Delord, Christophe Le Tourneau, Matthew S. Block, Gerardo Colon-Otero, Keith L. Knutson, Annette Tavernaro, Gisele Lacoste, Benoit Grellier, Xavier Noiriel, Thierry Huss, Bernard Burtin, Yoshiko Yamashita, Kousuke Onoue, Kazuhide Onoguchi, Brandon Malone, Olivier Lantz, Oliver Baker, Naoko Yamagata, Yuki Tanaka, Eric Quemeneur, Maud Brandely, Kaidre Bendjama. Feasibility and immunogenicity of adjuvant TG4050, a patient tailored cancer vaccine in head and neck and ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB205.

Abstract Objectives There have been recent advances assessing copeptin levels in adults with suspected disorders of vasopressin release. Very limited data exits on copeptin levels in children and infants, especially in a critically-ill hospitalized population where hyper- and hypo-natremia are very common. Our objective is to describe the institutional experience assessing copeptin levels in hospitalized infants and children with hyper- or hypo-natremia. Methods We performed a single-center retrospective case series of all infants, children, and adolescents who had an ultrasensitive plasma copeptin level obtained between 2019-2021. Results A total of 29 critically ill patients (6 infants) were identified with 38 % of patients having copeptin levels after neurosurgical procedures for tumors or trauma. Approximately 13/17 children with hypernatremia had central diabetes insipidus (central diabetes insipidus) to diagnose CDI, A copeptin level ≤ 4.9 pmol/L resulted in an 88 % sensitivity (95 % CI 47–99 %), and 66 % specificity (95 % CI 30–93 %). Amongst those with hyponatremia levels were more variable, 8/12 children had syndrome of inappropriate antidiuresis (SIAD) with copeptin levels ranging 4.7–72.6 pmol/L. Conclusions While difficult to conclude due to multiple limitations, this case series highlights that typical copeptin cutoffs used to diagnose DI in adults in an ambulatory setting may also translate to a critically-ill pediatric population. Large prospective studies are needed to confirm this observation. In addition, postoperative copeptin levels could potentially be utilized as an additional marker to predict permanent from transient DI, but much larger studies are needed. Further work is needed to establish normative copeptin levels in infants and patients with SIAD.

The present study examines connections between patient expectations and health-related quality of life. We explore a key distinction between expectations about general health and expectations for functional improvement. Patients were 1444 individuals with multiple conditions experiencing chronic pain who were seeking treatment at the Gastein Healing Gallery in Böckstein, near Bad Gastein, Austria. In addition to measures of expectations, patients completed measures of pain, mental and physical health, life satisfaction, fatigue, and sleep problems. Structural equation models were used to fit a latent variable model where both expectation variables were used to predict health-related quality of life. Results showed that expectations regarding potential functional improvement resulting from treatments at the Gastein Healing Gallery were associated with improved health-related quality of life. Expectations about general health improvements related to treatment were not associated with health-related quality of life. To facilitate optimal healing, clinicians may decide to emphasize expectations about functional recovery when discussing treatment methods similar to those offered at the Gastein Healing Gallery, and in so doing, health-related quality of life may benefit.

OBJECTIVE Infuse bone graft is a widely used osteoinductive adjuvant; however, the simple collagen sponge scaffold used in the implant has minimal inherent osteoinductive properties and poorly controls the delivery of the adsorbed recombinant human bone morphogenetic protein–2 (rhBMP-2). In this study, the authors sought to create a novel bone graft substitute material that overcomes the limitations of Infuse and compare the ability of this material with that of Infuse to facilitate union following spine surgery in a clinically translatable rat model of spinal fusion. METHODS The authors created a polydopamine (PDA)–infused, porous, homogeneously dispersed solid mixture of extracellular matrix and calcium phosphates (BioMim-PDA) and then compared the efficacy of this material directly with Infuse in the setting of different concentrations of rhBMP-2 using a rat model of spinal fusion. Sixty male Sprague Dawley rats were randomly assigned to each of six equal groups: 1) collagen + 0.2 µg rhBMP-2/side, 2) BioMim-PDA + 0.2 µg rhBMP-2/side, 3) collagen + 2.0 µg rhBMP-2/side, 4) BioMim-PDA + 2.0 μg rhBMP-2/side, 5) collagen + 20 µg rhBMP-2/side, and 6) BioMim-PDA + 20 µg rhBMP-2/side. All animals underwent posterolateral intertransverse process fusion at L4–5 using the assigned bone graft. Animals were euthanized 8 weeks postoperatively, and their lumbar spines were analyzed via microcomputed tomography (µCT) and histology. Spinal fusion was defined as continuous bridging bone bilaterally across the fusion site evaluated via µCT. RESULTS The fusion rate was 100% in all groups except group 1 (70%) and group 4 (90%). Use of BioMim-PDA with 0.2 µg rhBMP-2 led to significantly greater results for bone volume (BV), percentage BV, and trabecular number, as well as significantly smaller trabecular separation, compared with the use of the collagen sponge with 2.0 µg rhBMP-2. The same results were observed when the use of BioMim-PDA with 2.0 µg rhBMP-2 was compared with the use of the collagen sponge with 20 µg rhBMP-2. CONCLUSIONS Implantation of rhBMP-2–adsorbed BioMim-PDA scaffolds resulted in BV and bone quality superior to that afforded by treatment with rhBMP-2 concentrations 10-fold higher implanted on a conventional collagen sponge. Using BioMim-PDA (vs a collagen sponge) for rhBMP-2 delivery could significantly lower the amount of rhBMP-2 required for successful bone grafting clinically, improving device safety and decreasing costs.