Preliminary Clinical Experience Research Articles

Evaluating antitumor activity and response determinants to trastuzumab deruxtecan in pediatric solid tumors.

10049 Background: Trastuzumab deruxtecan (T-DXd) is an anti-HER2 antibody-drug conjugate (ADC) linked to a topoisomerase inhibitor FDA-approved for several indications, including the treatment of HER2+ breast and gastric cancer. Although HER2 amplification is uncommon in pediatric cancers, recent demonstration of T-DXd efficacy in HER2-low breast cancer patients prompted us to examine the potential clinical relevance of T-DXd in pediatrics by evaluating HER2 expression and activity of T-DXd in preclinical pediatric solid tumor models. Methods: Cell viability was assessed in a panel of histologically diverse pediatric solid tumor cell lines and 2 HER2-amplified adult cancer cell lines treated with T-DXd, payload (DXd), and a control IgG-ADC. HER2 protein expression in patient-derived xenograft (PDX) tumors was evaluated by immunohistochemistry (IHC) using 5 clinically validated anti-HER2 antibodies. RNAseq was performed on clinical (n=290) and PDX (n=184) tumors to determine relative expression of ERBB2. In vivo activity of T-DXd was evaluated in osteosarcoma (OS, n=10), Wilms tumor (WT, n=1) and malignant rhabdoid tumor (MRT, n=1) PDX models and a desmoplastic small round cell tumor (DSRCT) cell line xenograft model. Differences in tumor volume and time to disease progression was assessed and compared across treatments and models. Responses were correlated with HER2 expression by IHC. Results: In vitro, HER2-amplified control cell lines demonstrated a >30-fold reduction of IC50 when comparing T-DXd to ADC control. In contrast, the ADC control IC50 was nearly identical to T-DXd across all pediatric cancer cell lines, consistent with the absence of HER2 amplification in these models. We observed focal and membranous staining of HER2 by IHC in PDXs but was quite variable across antibodies tested: WT 0-17% HER2+ cases (n=6), MRT 0-40% (n=5), DSRCT 0-33% (n=24), OS 0-7% (n=30). ERBB2 gene expression was highest in DSRCT followed by WT, OS and MRT. In vivo efficacy studies demonstrated complete and partial responses in OS, WT, and DSRCT and improved disease control rates (OS: 67%, p=0.006, Mann-Whitney; WT: 100%; DSRCT: 100%). However, T-DXd and ADC control demonstrated similar activity in all tumor types with no consistent correlation between in vivo response and HER2 expression. Consistent with these preclinical studies, 4 patients with progressive DSRCT were treated with T-DXd via compassionate/off-label access with signs of clinical and radiographic responses. Conclusions: T-DXd shows significant preclinical antitumor activity across multiple pediatric solid tumors but little correlation with HER2 expression suggesting a mechanism of action similar to the clinical activity observed in HER2-low breast cancer. Xenograft efficacy studies and preliminary clinical experience with T-DXd in DSRCT patients warrant formal clinical trial investigation in this largely incurable disease.

Changing vistas of psychosis and antipsychotic drug dosing toward personalized management of antipsychotics in clinical practice.

To discuss current evidence on tapering antipsychotic drugs in view of changing vistas of psychosis, suggesting a provisional framework for safely tapering antipsychotic drugs to an optimal low dose, in collaboration with patients and their relatives, to promote functional recovery while preventing relapse. Paradigm shifts during recent years regarding the nature of psychotic disorders and the role of the dopamine system are discussed, including the positive effects of dopamine blockade in acute psychosis and the limitations and drawbacks of dopamine blockade regarding negative and cognitive symptoms after remission of positive symptoms. Recent advances in tapering strategies and upcoming ways to solve the dilemma between the need to prevent relapses with antipsychotics on the one hand and the need to minimize side effects by tapering these drugs on the other are presented. Modern tapering strategies appear to reduce relapse risk to acceptable levels and offer a feasible personalized option to find the least effective dose to treat and prevent positive symptoms without redundant side effects and functional incapacity. These findings need replication, and several trials that might provide more certainty are on their way. Preliminary evidence and clinical experience indicate that personalized dose reduction of antipsychotics is feasible and safe if carried out in close collaboration with patients and their relatives, according to a provisionally suggested framework presented here. These preliminary directions still must be confirmed, revised, and adjusted according to upcoming trial results. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Tailoring Radiation Therapy for Patients With Limited Cutaneous T Cell Lymphoma: Preliminary Clinical Experience With Subtotal Skin Electron Therapy.

Total skin electron beam therapy (TSEBT) is an effective treatment for managing cutaneous T-cell lymphoma (CTCL), but may result in unnecessary toxicity. With the production of a custom rolling shield holding a configurable stack of plastic slats to block uninvolved skin, we implemented a program for subtotal skin electron beam therapy (STSEBT). We report our preliminary experience with STSEBT vs. TSEBT to manage CTCL. A retrospective review of 32 CTCL patients who were treated at a single institution between February 28th, 2017, and May 25th, 2022, was completed. Of these cases, seven patients received STSEBT and 25 received TSEBT. Thirty-two patients underwent a course of STSEBT or TSEBT. The median follow-up was 465 days and the median age at diagnosis was 70.8 years. Stage distribution was as follows: one (3%) IA, 16 (50%) IB, 6 (19%) IIB, two (6%) IIIA, five (16%) IVA, and two (6%) IVB. The overall response rate was 96%. For patients receiving TSEBT (n=25), three (12%), 10 (40%), and 11 (44%) had a CR, NCR, and PR, respectively. For the patients receiving STSEBT, four (57.1%), three (42.9%), and zero (0%) had a CR, NCR, and PR, respectively. There was one patient (4%) with no response. Cumulative incidence of progressive skin disease requiring additional electron therapy at three months was 21.1% [IQR=8.6, 51.5%], 36.8% [IQR=20, 68%] at six months, and 57.9% [IQR=38.5, 87.1%] at one year. Low rates of toxicities were recorded. This analysis demonstrated that treatment of CTCL patients with low disease burden with STSEBT results in similar overall response and time to progression compared to treatment with TSEBT.

Rapid brain MRI for image-guided ventricular catheter placement in pediatric patients: protocol and preliminary clinical outcomes.

Neuronavigation is a useful adjunct for catheter placement during neurosurgical procedures for hydrocephalus or ventricular access. MRI protocols for navigation are lengthy and require sedation for young children. CT involves ionizing radiation. In this study, the authors introduce the clinical application of a 1-minute rapid MRI sequence that does not require sedation in young children and report their preliminary clinical experience using this technique in their pediatric population. All patients who underwent ventricular catheter placement at a children's hospital using a rapid noncontrast MRI protocol, standard MRI, or head CT from July 2021 to August 2023 were included. Type of procedure, etiology of hydrocephalus, ventricle configuration and size, morphology of ventricles, need for adjunctive intraoperative ultrasound, duration of procedure, accuracy of catheter placement, and need for proximal revision within 90 days were retrospectively recorded and compared across imaging modalities. Sixty-eight patients underwent 83 procedures: 21 underwent CT navigation, 29 standard MRI, and 33 rapid MRI. Patients who received standard MRI more often had tumor etiology, while those who underwent CT and rapid MRI had posthemorrhagic etiology (χ2 = 13.04, p = 0.042). Intraoperative ultrasound was required for 1 patient in the standard MRI group and 1 patient in the CT group. There was no difference in procedure time across groups (p = 0.831). On multivariable analysis, procedure time differed by procedure type, where external ventricular drain placement and proximal revision were faster (p < 0.001 and p < 0.028, respectively). Proximal revision due to obstruction within 90 days occurred in 3 cases (in the same patient with complex loculated hydrocephalus) in the rapid MRI group and 2 cases in the CT group. Although this study was not powered for statistical inference, the authors report on the clinical use of a 1-minute rapid MRI sequence for neuronavigation in hydrocephalus or ventricular access surgery. There were no instances in which intraoperative ultrasound was required as an adjunct for procedures navigated with rapid MRI, and intraoperative time did not differ from that of standard navigation protocols.

Use of a Novel Buffered Hypertonic Saline Solution for Fluid Replacement and Resuscitation During Spinal Surgery in Adolescents.

During major orthopedic procedures, such as posterior spinal fusion (PSF), isotonic fluids, colloids, starches, or gelatins are commonly used to replace the preoperative fluid deficit and provide ongoing fluid resuscitation. Given recent concerns regarding the potential adverse physiologic effects of albumin solutions, we have modified our intraoperative practice to include the use of a novel 2% buffered hypertonic saline solution during major orthopedic procedures. We present our preliminary clinical experience with this novel fluid for intraoperative resuscitation and its impact on limiting the use of 5% albumin. A retrospective review was performed to identify patients who received 2% buffered hypertonic saline during PSF. The intraoperative course of these patients was compared to case-matched control patients who received standard care with isotonic fluids plus 5% albumin as an adjunct for intravascular resuscitation. The study cohort included 23 patients who received 2% buffered hypertonic saline and 25 in the case-matched control group. There was no difference in the volume of intraoperative isotonic crystalloid fluids, estimated blood loss, and urine output between the two groups. In the control cohort, 19 of 25 patients (76%) received 5% albumin compared to only six of 23 patients (26%, P = 0.0005) in the 2% buffered hypertonic saline group. The final pH was higher in the patients that received 2% buffered hypertonic saline than in the control group (7.40 ± 0.03 versus 7.36 ± 0.06, P = 0.0131). Additionally, the starting and final serum sodium values were higher in the patients that received 2% buffered hypertonic saline, although no difference was noted in the mean change from the starting value (average increase of 2 mEq/L in both groups). Use of a novel 2% buffered hypertonic saline solution for intraoperative resuscitation during major orthopedic procedures decreases the need for 5% albumin while avoiding the development of hyperchloremic metabolic acidosis which may occur with standard sodium chloride solutions.

A Metabolically Optimized, Noncytotoxic Low-Dose Weekly Decitabine/Venetoclax in MDS and AML

Abstract Purpose: Venetoclax (VEN) added to the hypomethylating agents (HMA) decitabine or azacitidine is the new standard of care for elderly patients with acute myeloid leukemia (AML) and is being evaluated in myelodysplastic syndrome (MDS). Current dosing of HMA/VEN relies on leukemia suppression through cytotoxicity which also impacts normal hematopoiesis. A regimen using once-weekly low-dose decitabine (LDDec) has demonstrated activity in myeloid malignancies. To overcome the severe myelosuppression often seen with HMA/VEN, we evaluated a once-weekly dosing regimen of VEN and LDDec in elderly and/or frail patients who were felt less likely to tolerate severe myelosuppression. Patients and Methods: This is a retrospective, single-center analysis of patients with AML, MDS, or chronic myelomonocytic leukemia treated with a once-weekly LDDec/VEN regimen. We also compare this regimen with a cohort treated with standard dosing HMA/VEN. Results: In a retrospective cohort of 39 patients, the overall response rate for patients receiving LDDec/VEN for first-line AML and MDS was 88% and 64%, respectively. In patients with TP53 mutations, the composite complete response rate was 71% and the median overall survival was 10.7 months. When compared with 36 patients receiving standard dose HMA/VEN, the LDDec/VEN patients had a longer time on therapy (175 vs. 78 days; P = 0.014) and a trend toward a higher rate of transfusion independence (47% vs. 26%; P = 0.33). Neutropenic fever occurred in 31% of patients, with a median of one hospitalization at any point during treatment. Conclusions: This preliminary clinical experience, although retrospective, provides proof-of-activity of noncytotoxic DNA methyltransferase 1–targeting by allowing frequent, sustained drug exposure often not possible with standard HMA/VEN regimens.

Efficacy and Safety of Axiostat® Hemostatic Dressing in Aiding Manual Compression Closure of the Femoral Arterial Access Site in Patients Undergoing Endovascular Treatments: A Preliminary Clinical Experience in Two Centers.

Hemostasis of the femoral arterial access site by manual compression or a vascular closure device is critical to the safe completion of any endovascular procedure. Previous investigations evaluated the hemostatic efficacy at the radial access site of some chitosan-based hemostatic pads. This study aims to assess the efficacy and safety of a new chitosan-based hemostatic dressing, namely Axiostat®, in aiding manual compression closure of the femoral arterial access site in patients undergoing endovascular treatments. Furthermore, the outcomes were compared with evidence on manual compression alone and vascular closure devices. This investigation is a two-center retrospective analysis of 120 consecutive patients who had undergone, from July 2022 to February 2023, manual compression closure of the femoral arterial access site aided by the Axiostat® hemostatic dressing. Endovascular procedures performed with introducer sheaths ranging from 4 Fr to 8 Fr were evaluated. Primary technical success was achieved in 110 (91.7%) patients, with adequate hemostasis obtained in all cases of prolonged manual compression requirements. The mean time-to-hemostasis and time-to-ambulation were 8.9 (±3.9) and 462 (±199) minutes, respectively. Clinical success was achieved in 113 (94.2%) patients, with bleeding-related complications noted in 7 (5.8%) patients. Manual compression aided by the Axiostat® hemostatic dressing is effective and safe in achieving hemostasis of the femoral arterial access site in patients undergoing endovascular treatment with a 4-8 Fr introducer sheath.

Preliminary clinical observation of double C-arm digital subtraction angiography guidance during transjugular intrahepatic portosystemic shunt placement

BackgroundThis study aimed to investigate the safety, preliminary clinical experience, and technical advantages of double C-arm digital subtraction angiography -assisted portal vein puncture for transjugular intrahepatic portosystemic shunt.MethodsClinical data of 25 patients with portal hypertension caused by liver cirrhosis were retrospectively analyzed from January 2021 to June 2022. The fluoroscopy time, puncture time, mean portosystemic pressure gradient, dose area product, and intraoperative and postoperative complications were recorded.ResultsTransjugular intrahepatic portosystemic shunt was performed in all 25 patients, with a success rate of 100%. The fluoroscopy time, puncture time, and dose area product were 33.6 ± 8.5 min, 9.1 ± 5.7 min, and 126 ± 53 Gy·cm2, respectively. The mean portosystemic pressure gradient decreased from 22.5 ± 6.3 mmHg to 10.5 ± 2.3 mmHg (p < 0.01). No serious intraoperative and postoperative complications were found.ConclusionDouble C-arm digital subtraction angiography-assisted portal vein puncture is safe and feasible in transjugular intrahepatic portosystemic shunt operation. It can reduce the difficulty of the operation and possesses evident technical advantages.

A Synthetic Hybrid-scale Fiber Matrix for Complex Surgical Wounds: Consensus Guidelines

Based on their own clinical experience and review of the available peer-reviewed data, the authors developed a consensus opinion on the use of an SHSFM for open wounds. The matrix has features such as varying pore sizes and fibers (ie, hybrid-scale) and is indicated for the treatment of open wounds. This report describes the design and utility of the SHSFM, its mechanism of action, and the methods of application, as well as clinical outcomes. The authors discuss their own experience and review of the published literature, then describe their protocols and rationale for the use of the SHSFM. These consensus statements include recommendations regarding appropriate wounds for use of the SHSFM, use of other wound therapies in conjunction with the SHSFM, reapplication rates, preparation methods, and additional discussions of appropriate use. This report is not a literature review, but rather is a statement of preliminary clinical experience. The consensus statements indicate that the SHSFM may be used to treat a variety of wounds and can be used to stage wounds to closure via skin grafts or by secondary intention.

Use of the National Institutes of Health pain education cases to frame an interprofessional activity with healthcare professional students

Creating authentic learning experiences in pain education is both challenging and important for healthcare educators. While didactic lecture about pain management is a common pedagogical approach, interactive experiences are less common due to the need for high level coordination. The purpose of this article is to share an interactive educational activity designed to build student understanding of treatment for persistent pain. Interprofessional (IP) groups discussed respective roles and responsibilities during a case-based care team meeting and created a comprehensive care plan for a patient experiencing pain using contemporary cases, based in practice. Students utilized knowledge obtained from their professional coursework and experience from preliminary clinical experience to share with other healthcare professional students their discipline-specific perspective on treating persistent pain. Through sharing of scope of practice information and discipline specific experience, the IP groups created an extensive and collaborative pain management plan. Outcomes of the activity included a presentation of the case, use of ISBAR (Identity, Situation, Background, Assessment, Recommendation) and assessment of their own learning and evaluation of the activity.

CFR-PEEK Pedicle Screw Instrumentation for Spinal Neoplasms: A Single Center Experience on Safety and Efficacy

(1) Background: Surgery for spinal metastases has gained a decisive role in modern oncological treatment. Recently, carbon-fiber-reinforced (CFR) polyethyl-ether-ether-ketone (PEEK) pedicle screw systems were introduced, reducing artifacts on imaging and showing less perturbation effects on photon radiation. Preliminary clinical experience with CFR-PEEK implants for spinal metastases exists. The aim of this monocentric study is to report on the safety and efficacy of CFR-PEEK pedicle screw systems for spinal neoplasms in a large cohort of consecutive patients. (2) Methods: We retrospectively analyzed prospectively the collected data of consecutive patients being operated on from 1 August 2015 to 31 October 2021 using a CFR-PEEK pedicle screw system for posterior stabilization because of spinal metastases or primary bone tumors of the spine. (3) Results: We included 321 patients of a mean age of 65 ± 13 years. On average, 5 ± 2 levels were instrumented. Anterior reconstruction was performed in 121 (37.7%) patients. Intraoperative complications were documented in 30 (9.3%) patients. Revision surgery for postoperative complications was necessary in 55 (17.1%) patients. Implant-related complications, such as intraoperative screw breakage (3.4%) and screw loosening (2.2%), were rare. (4) Conclusions: CFR-PEEK is a safe and efficient alternative to titanium for oncological spinal instrumentation, with low complication and revision rates in routine use and with the advantage of its radiolucency.

Evaluation of the apposition in unruptured aneurysms treated with flow diverters by optical coherence tomography: Preliminary clinical experience.

The risk of perioperative stroke and the rate of occlusion of long-term aneurysms in the treatment of unruptured aneurysms with flow diverters (FDs) are affected by stent apposition. Optical coherence tomography (OCT) may be an optional technique in evaluating apposition. To explore the feasibility of the OCT imaging technique in evaluating stent apposition in the clinical application of the FD for unruptured aneurysms. OCT and Vaso CT were used in patients with indications for surgery to treat unruptured aneurysms with the FDs, to evaluate the apposition of the FDs after fully released, and to analyze OCT images for FDs apposition and compare with corresponding Vaso CT images. A total of four patients were enrolled, and OCT found malapposition after FDs placement in all four patients, and the maximum gap between the stent and vascular wall ranged from 0.68 to 1.95 mm and the length of malapposition ranged from 1.80 to 7.40 mm. However, Vaso CT found malapposition only in two of the four patients and missed malapposition near aneurysm in all three patients treated by the FD combined with coiling and could not accurately evaluate the maximum gap and the length of the malapposition. The optical coherence tomography technique is a possible approach to evaluate apposition after the treatment of unruptured aneurysms by the FDs.

Utility of Large Diameter Visible Trephine in Percutaneous Endoscopic Lumbar Interbody Fusion: A Technical Report

In this study, a large diameter visible trephine was designed and used in percutaneous endoscopic lumbar interbody fusion to increase endoscopic bone decompression efficiency. Large diameter visible trephine-related technical notes and preliminary clinical experience are described. A large diameter visible trephine was designed with normal diameter visible trephine as template. A total of 38 patients with lumbar degenerative diseases who underwent single-level percutaneous endoscopic lumbar interbody fusion with large or normal diameter visible trephine were included into a retrospective study. Operation time, bone decompression time, blood loss, intraoperative fluoroscopy, bone decompression fluoroscopy, and dura or nerve injury cases were recorded and analyzed statistically. Visual Analog Scale (VAS) scores and Oswestry Disability Index (ODI) were used to analyze the clinical outcomes of the 2 groups. The baseline data of the 2 groups were statistically similar. There was no significant difference in postoperative VAS and ODI scores between the 2 groups. Operation time and bone decompression time of large diameter visible trephine group were significantly shorter than that of normal diameter visible trephine group (P < 0.05). Intraoperative fluoroscopy times and bone decompression fluoroscopy times of large diameter visible trephine group were significantly more than that of normal diameter visible trephine group (P < 0.05). Blood loss of the 2 groups were not statistically different. There were no dura or nerve injury cases in the 2 groups. For percutaneous endoscopic lumbar interbody fusion, the large diameter visible trephine is a safe and efficient endoscopic bone decompression tool under fluoroscopic guidance.

Additive Manufacturing of Lithium Disilicate with the LCM Process for Classic and Non-Prep Veneers: Preliminary Technical and Clinical Case Experience.

Background: ceramic veneers, crowns, and other types of restorations are often made using either the press heating technique or the subtractive method. The advent of lithography-based ceramic manufacturing (LCM) allows for the manufacturing of such restorations in an additive way. Methods: this concept paper describes the first clinical experience in the application of LCM lithium disilicate restorations in vivo for the manufacturing of classic veneers for a patient with severe tooth wear. The applied restorations were analyzed in terms of their marginal fit in metrology software (Geomagic Control X, 3D Systems). Furthermore, the feasibility of 3D printing of non-prep veneers with a 0.1 mm thickness was tested. Results: the classic LCM lithium disilicate veneers were tried in the mouth cavity and demonstrated adequate esthetics and a sufficient marginal fit of 100 µm. Furthermore, the non-prep veneers with a 0.1 mm thickness could be successfully printed using LCM technology and also demonstrated an adequate fit on the model in vitro. Conclusions: the described technical approach of lithium disilicate 3D printing with LCM technology may pose a valid alternative to subtractive and analog manufacturing and be a game-changing option with the use of additive chairside ceramic fabrication.

Subcutaneous finger cardioverter-defibrillator in low weight paediatric patients: a case series.

Placement of traditional transvenous implantable cardioverter defibrillator (ICD) system in low-weight children is often difficult because of their vessel size, the elevated risk of lead malfunction and failure, children's growth and various anatomic constraints, creating the need for alternative solutions. Subcutaneous array leads combined with an abdominally placed ICD device can minimize the surgical approach. In this case series, we analyse the data behind indications for subcutaneous finger cardioverter defibrillator (SFCD) and discuss the preliminary clinical experience in low-weight children. We considered 4 consecutive children (mean age 3.9 years, range 3-5.5 years, mean body weight 17.6 Kg, range 14-23 Kg) who underwent SFCD implant from April 2016 to August 2020. All patients showed a good compliance to the device system with no complications (infections or skin erosions). No patients experienced in the observation period (mean time 44.5±21.5 months) sustained ventricular arrhythmias requiring shocks. No inappropriate shocks released by the device occurred. No significant changes were observed in LET (lowest energy tested) performed around 24 months of follow-up. All patients showed a good compliance and stable atrio-ventricular sensing and pacing thresholds. In smaller children in whom a transvenous approach is not feasible or not possible for anatomic reasons, the SFCD appears to be a safe method to prevent SCD with little surgical trauma and preservation of an intact vascular system, providing an adequate bridge to transvenous ICD or subcutaneous ICD implant late in the life.

Preliminary Clinical Experience of Molnupiravir to Prevent Progression of COVID-19 in Kidney Transplant Recipients.

Recently, different therapeutic lines have been tried in the initial stage of the disease of COVID-19, including remdesivir and molnupiravir. There is scarce evidence on the efficacy and safety of molnupiravir in kidney transplant recipients (KTRs). ingle-center prospective cohort study' all adult KTRs diagnosed with COVID-19 and treated with molnupiravir or remdesivir from January to April 2022 were included. Nine KTRs with SARS-CoV-2 (Omicron variant) infection and mild symptoms received molnupiravir in an outpatient basis and were compared with a cohort of similar patients treated with remdesivir (n = 7). Three patients in the molnupiravir cohort were in the early posttransplant period and received a basiliximab (n = 2) or antithymocite globulin-based induction (n = 1). One of the patients had been treated with methylprednisolone bolus and antithymocite globulin for an episode of acute rejection in the previous months. They were all vaccinated with mRNA vaccines' and all but 1 had serological response. Only one of the patients experienced clinical worsening despite molnupiravir treatment and developed pneumonia requiring hospital admission. None of the patients suffered adverse effects attributed to molnupiravir' and no adjustment of tacrolimus dose was needed. None of the patients treated with remdesivir progressed in COVID-19 severity. Our study suggests that KTRs with SARS-CoV-2 infection under treatment with molnupiravir have a good clinical evolution with a probable lower risk for hospitalization and no adverse effects. At the renal level, molnupiravir was well tolerated, with no evidence of nephrotoxicity secondary to the drug nor interactions with the immunosuppressive therapy.

Preliminary Clinical Experience with a High-Definition Three Dimensional Exoscope for Spinal Surgery.

We retrospectively evaluated spinal surgeries performed using the high-definition three-dimensional exoscopic system, which became available at our institution in August 2020. Eleven patients (4 with cervical disease and 7 with lumbar disease) underwent surgery with the system. There were no surgical complications related to the system, and the results were satisfactory. The small, flexible camera of the exoscope allows the surgeon to view the surgical field from various angles, facilitating both the approach and technique. In addition, it allows the surgeon to operate in an upright position without strain on the head and neck. Although further surgical experience is needed, this system has the potential to improve the visualization of the surgical field in spinal surgery.

LGG-62. Weight change in pediatric patients treated with MEK inhibitors: a retrospective cohort study

BACKGROUND: MEK inhibition is an emerging treatment strategy in pediatric tumors characterized by activation of the Ras-Raf-MEK-ERK pathway, including low-grade glioma (LGG) and neurofibromatosis 1 (NF1)-associated tumors. Preliminary clinical experience suggests that MEK inhibitors (MEKi) may be associated with weight gain in children, which has not been a reported toxicity in adults. METHODS: 35 patients > 1 and < 21 years old treated at CHLA with MEKi between October 2013 and May 2019 were identified. Data was collected at t = 0 (baseline), t = 3 months, t = 6 months, t = 12 months, and t = 24 months, as well as pre- and post-treatment time points. Weight change was categorized as no change (change in Z-score [-0.25, +0.25]), weight gain (change in Z-score > 0.25), and weight loss (change in Z-score > -0.25). RESULTS: Weight gain and weight loss were seen in 11 (34.4%) and 8 (25%) patients, respectively, after 6 months on therapy. Weight gain reversed in 4 out of 5 patients with post-treatment data. There was no clear association between weight outcome and hypothesized covariates (including hypothalamic location and NF1 status). Notably, significant weight gain was seen across baseline weight spectrum, including patients who had underweight and severely overweight BMI percentiles at baseline. CONCLUSION: Our findings preliminarily suggest that MEK inhibition may be associated with clinically significant weight change, especially weight gain, in a subset of children and young adults. Reversal upon drug cessation suggests a causal relationship. Further prospective and mechanistic investigation is needed.

Preliminary Clinical Surgical Experience with Temporary Simultaneous Use of an Endoscope during Exoscopic Neurosurgery: An Observational Study.

The use of an endoscope in exoscopic transcranial neurosurgery for skull-base lesions has not yet been investigated. Thus, this study aimed to investigate the advantages, disadvantages, and safety of “simultaneous temporary use of an endoscope during exoscopic surgery” (exo-endoscopic surgery (EES)). Consecutive exo-endoscopic surgeries performed by experienced neurosurgeons and assistants were analyzed. Surgical complications and time were compared with previous consecutive microsurgeries performed by the same surgeon. A questionnaire survey was conducted on 16 neurosurgeons with experience in both “temporary simultaneous use of endoscope during microscopic surgery” (micro-endoscopic surgery (MES)) and EES. EES was performed in 18 of 76 exoscopic surgeries, including tumor removal (n = 10), aneurysm clipping (n = 5), and others (n = 3). There were no significant differences in operative time, anesthesia time, or complications from microsurgery by the same operator. According to the questionnaire survey results, compared with MES, EES had a wider field of view due to its lack of an eyepiece, was easier when loading and unloading instruments into and out of the surgical field, and was more suitable for the simultaneous observation of two fields of view. Overall, 79.2% of surgeons indicated that EES may be better suited than MES to simultaneously observe two fields of view.

Preliminary clinical experience of the novel transcatheter aortic valve system Prizvalve® for the treatment of severe aortic stenosis

Objective: To evaluate the safety and efficacy of transcatheter aortic valve implantation (TAVI) with the novel Prizvalve® system in treating severe aortic stenosis. Methods: This is a single-center, prospective, single-arm, observational study. A total of 11 patients with severe aortic stenosis with high risk or inappropriate for conventional surgical aortic valve replacement (SAVR) were included, and TAVI was achieved with the Prizvalve® system between March 2021 and May 2021 in West China Hospital. Transthoracic echocardiography (TTE) was performed immediately after prosthesis implantation to evaluate mean transaortic gradient and maximal transaortic velocity. The device success rate was calculated, which was defined as (1) the device being delivered via the access, deployed, implanted and withdrawn, (2) mean transaortic gradient<20 mmHg (1 mmHg=0.133 kPa) or a maximal transaortic velocity<3 m/s post TAVI, and without severe aortic regurgitation or paravalvular leak post TAVI. TTE was performed at 30 days after the surgery, and all-cause mortality as well as the major cardiovascular adverse events (including acute myocardial infarction, disabling hemorrhagic or ischemic stroke) up to 30 days post TAVI were analyzed. Results: The age of 11 included patients were (78.1±6.3) years, with 8 males. A total of 10 patients were with NYHA functional class Ⅲ or Ⅳ. Devices were delivered via the access, deployed, implanted and withdrawn successfully in all patients. Post-implant mean transaortic gradient was (7.55±4.08) mmHg and maximal transaortic velocity was (1.78±0.44) m/s, and both decreased significantly as compared to baseline levels (both P<0.05). No severe aortic regurgitation or paravalvular leak was observed post TAVI. Device success was achieved in all the 11 patients. No patient died or experienced major cardiovascular adverse events up to 30 days post TAVI. Mean transaortic gradient was (9.45±5.07) mmHg and maximal transaortic velocity was (2.05±0.42) m/s at 30 days post TAVI, which were similar as the values measured immediately post TAVI (both P>0.05). Conclusions: TAVI with the Prizvalve® system is a feasible and relatively safe procedure for patients with severe aortic stenosis and at high risk or inappropriate for SAVR. Further clinical studies could be launched to obtain more clinical experience with Prizvalve® system.