Injection Site Research Articles

Efficacy of foam sclerotherapy with polidocanol for the management of oral venous malformations.

The present aimed to examine the effectiveness of polidocanol-based foam sclerotherapy for oral venous malformations (OVMs). The present study performed a retrospective analysis of patients with OVMs who underwent sclerotherapy using polidocanol. Patients achieving the complete resolution of OVM were categorized as having a complete response (CR), those with a reduction in size from the initial diagnosis were categorized as having a partial response (PR), those with no change in size as stable disease (SD), and those with an increase in size as progressive disease (PD). A total of 16 patients, comprising 4 males and 12 females, underwent treatment with polidocanol foam therapy, covering 22 affected areas. The treatment administered resulted in CR in 6 cases and PR in 10 cases, with no instances of SD or PD. Apart from localized injection site pain or swelling, there were no severe side-effects reported, such as circulatory dynamic changes or skin necrosis. On the whole, these findings underscore the effectiveness of foam sclerotherapy with polidocanol as a viable treatment for venous malformations in the oral and maxillofacial regions.

Monitoring Oxford-AstraZeneca COVID-19 vaccine Side Effects in Faridpur, Bangladesh: A Prospective Study

The Oxford-AstraZeneca COVID-19 vaccine is effective in preventing illness and death from COVID-19. In this study, we aimed to evaluate the safety of the Oxford-AstraZeneca COVID-19 vaccine in a population in Faridpur, Bangladesh. The study population included individuals who received both doses of the vaccine from Bangabandhu Sheikh Mujib Medical College Hospital in Faridpur. We followed up with these individuals via phone interviews one week and one month after each vaccination to gather information about side effects. We found that the overall incidence of systemic and injection site side effects after the first and second doses was 36.5% and 34.7%, and 68.2% and 61.3%, respectively, among the 2256 studies population. The most common systemic side effects were fatigue, fever, and muscle pain, while the most common injection site symptoms were tenderness, pain, and redness. These side effects generally resolve within 24-72 hours after vaccination. Only a small percentage of individuals (1.3% after the first dose and 0.5% after the second dose) sought medical attention for their side effects. We also found that individuals with a history of chronic disease and those who had a history of COVID-19 symptoms had a significantly higher likelihood of experiencing side effects. In conclusion, the Oxford-AstraZeneca COVID-19 vaccine was generally safe in this population, with a low incidence of side effects requiring medical attention. Bangabandhu Sheikh Mujib Med. Coll. J. 2024;3(1):16-21

Extensive Cerebral Venous Thrombosis following by COVID-19 Vaccine with Concomitant COVID-19 Infection

Coronavirus disease 2019 (COVID-19) vaccines have been introduced to the masses for just over two years. Majority reported adverse events post vaccination are minor side effect such as pain or inflammation at local injection site. Serious side effects such as thrombotic events or myocarditis are rarely reported. Cerebral venoussinus thrombosis (CVST) is a thrombotic complication that may occur within one to two weeks from vaccine administration. W illustrated a case from our centre involving a healthy young lady who presented with headache and an episode of seizure following by vaccination. She was concurrently diagnosed with CVST and COVID-19 infection later with the aid of neuroimaging. The patient's normal platelet count made the diagnosis of vaccine induced immune related thrombotic thrombocytopenia unlikely. While serious adverse events are reported, such as our case, this should not support the growing vaccine hesitancy among the public as its benefits still greatly outweigh its risk at this juncture.

The early safety profile of simultaneous vaccination against influenza and Respiratory Syncytial Virus (RSV) in patients with high-risk heart failure

The safety of simultaneous vaccination for Respiratory Syncytial Virus (RSV) and influenza in vulnerable high-risk heart failure (HF) patients remains unclear. In an open-label, prospective study, 105 patients received concurrent influenza (Vaxigrip Tetra, season 2023/2024, Sanofi) and RSV (Arexvy, GSK) vaccinations from September 15th to November 17th, 2023. Adverse events were collected on the fourth-day post-vaccination. Overall, the vaccination was well tolerated, with the most common reaction being injection site pain (63 %). General symptoms occurred in 33 % of patients, predominantly fatigue (23 %), myalgia (12 %), and headache (9 %). Grade 3 reactions were observed in 6 % of patients, and a few experienced temperature elevation or flu-like symptoms, managing them with antipyretics. Notably, there were no exacerbations of HF, hospitalizations, or deaths within a week post-vaccination. This study indicates the safety of simultaneous influenza and RSV vaccination in high-risk HF patients, with a low incidence of mild adverse events.

Clues to the Design of Aggregation-Resistant Insulin from Proline Scanning of Highly Amyloidogenic Peptides Derived from the N-Terminal Segment of the A-Chain.

Insulin aggregation poses a significant problem in pharmacology and medicine as it occurs during prolonged storage of the hormone and in vivo at insulin injection sites. We have recently shown that dominant forces driving the self-assembly of insulin fibrils are likely to arise from intermolecular interactions involving the N-terminal segment of the A-chain (ACC1-13). Here, we study how proline substitutions within the pilot GIVEQ sequence of this fragment affect its propensity to aggregate in both neutral and acidic environments. In a reasonable agreement with in silico prediction based on the Cordax algorithm, proline substitutions at positions 3, 4, and 5 turn out to be very effective in preventing aggregation according to thioflavin T-fluorescence-based kinetic assay, infrared spectroscopy, and atomic force microscopy (AFM). Since the valine and glutamate side chains within this segment are strongly involved in the interactions with the insulin receptor, we have focused on the possible implications of the Q → P substitution for insulin's stability and interactions with the receptor. To this end, comparative molecular dynamics (MD) simulations of the Q5P mutant and wild-type insulin were carried out for both free and receptor-bound (site 1) monomers. The results point to a mild destabilization of the mutant vis à vis the wild-type monomer, as well as partial preservation of key contacts in the complex between Q5P insulin and the receptor. We discuss the implications of these findings in the context of the design of aggregation-resistant insulin analogues retaining hormonal activity.

Abstract 4135: First demonstration of magnetic particle imaging for sentinel lymph node identification

Abstract Sentinel Lymph Node (LN) biopsy involves the identification and surgical removal of the first LN(s) that drain from a primary tumor to evaluate for metastasis by histopathology [1]. For several tumor types, the standard of care is to manage the regional LN basin separately from the primary tumor. For head and neck cancer, melanoma, and complex breast cancer cases, pre-surgical imaging is required to determine the number and location of LN(s) to remove. Most sentinel LN biopsies are performed with nuclear imaging, which relies on short-lived radiotracers and can have poor image quality, making it challenging to identify sentinel LNs in complex anatomies. An alternative and non-inferior workflow uses a non-radioactive iron oxide magnetic tracer (ferucarbotran) with a magnetic probe [2], however this tool can only be used intraoperatively. In this abstract we introduce magnetic particle imaging (MPI) as a pre-surgical imaging technology that detects iron oxides with high sensitivity at mm-scale resolution [3]. Our objective is to demonstrate that MPI provides sensitive and quantitative tracking of ferucarbotran pharmacokinetics from four anatomical sites to primary draining LNs in mice. Methods: Ferucarbotran was administered intradermally to C57BL/6 mice at a standard clinical dose of 0.675 mg Fe/kg to the forepaw, hindpaw, or base of tail, or tongue (n = 4). Full-body 2D and 3D imaging was performed after 20 mins, 24 h, and 48 h, and 144 h using MOMENTUM imager (Magnetic Insight Inc.). MPI signal was quantified at the injection site and draining LNs. LNs of interest were extracted to verify MPI signals ex vivo then were processed for Perl’s Prussian iron staining. Results: After 20 minutes, MPI signal was seen at the injection site and primary LNs. The pharmacokinetics of ferucarbotran to LNs varied based on administration site. For hindpaw, signal was present in the popliteal LN (1.4% of tracer). For forepaw, ferucarbotran accumulated in the primary axillary LN (9%). For base of the tail, signal was observed in inguinal LN (2%). For tongue, MPI signal was detected in cervical LNs (14%). In all mice, MPI signal at the injection site decreased over time and signal in primary LNs persisted for at least 6 days. Conclusions: We demonstrated MPI is a quantitative, hotspot imaging technique for identifying primary LNs. As iron oxide tracer pharmacokinetics varies with injection site, this imaging technique could provide fundamental information required for surgical planning. Unlike nuclear imaging, persistence of MPI signal for several days provides tremendous flexibility in clinical workflow and introduces the potential for an image-guide delayed SLN biopsy [4] . This preclinical LN imaging is timely as our team is actively building and testing the world’s first large-bore, clinical-scale MPI scanner.[1] Leong SP, Clin Exp Metastasis (2022). [2] Alvarado MD, et al. Ann Surg Oncol (2019). [3] Sarnitas EU, et al. J Magn Reson (2014). [4] Karakatsanis A, et al. Ann Surg Oncol (2023). Citation Format: Olivia C. Sehl, A. Rahman Mohtasebzadeh, Kelvin Guo, Petrina Kim, Benjamin Fellows, Marcela Weyhmiller, Paula J. Foster, Patrick W. Goodwill, Joan M. Greve. First demonstration of magnetic particle imaging for sentinel lymph node identification [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4135.

Abstract 3185: Glatiramer acetate enhances tumor retention and mitigates systemic toxicity of toll-like receptor 9 agonists as intratumoral immunotherapy

Abstract Pathogen-associated molecular patterns (PAMP) are conserved molecular structures produced by microorganisms that are recognized as foreign by receptors of the innate immune system. Unmethylated cytosine-guanine oligodeoxynucleotides (CpG ODNs) are a storied drug class from the PAMP family that ligates Toll-like receptor 9 (TLR9). CpG ODNs have shown promising antitumor effects in preclinical studies by inducing potent pro-inflammatory immune responses. However, there are still practical challenges that have hindered clinical success, including inefficient in vivo delivery and severe immune-related toxicities caused by systemic exposure to CpG. We previously identified that glatiramer acetate (GA), an FDA-approved, lysine-rich polypeptide, could be applied as a cationic drug delivery vector for CpG delivery proximal to the injection site while mitigating systemic release of pro-inflammatory cytokines. To dive into the mechanism and evaluate pharmacological efficacy in more pathological models that simulate colorectal carcinoma, we validated the biodistribution of GA-CpG complexes (or R4B) and explored their safety and antitumor immunity in multiple mouse colorectal carcinoma models. In the CT26 single tumor model, intratumoral R4B treatment displayed comparable antitumoral efficacy as CpG treatment. Genome-wide transcriptome analysis showed that R4B treatment elicited much more prominent immune system response pathways in both lesions and spleens. The biodistribution study proved that R4B localized and gradually released CpG around the injection site while ‘naked’ CpG diffused away from the injection site quickly. In the CT26 dual tumor-bearing model, intratumoral administration of R4B generated systemic immune efficacy that led to an abscopal effect on distant untreated cancers, comparable to treatment with CpG alone. Notably, R4B treatment accomplished these effects with greatly mitigated systemic pro-inflammatory cytokines compared to CpG alone. These data help further elucidate the noncanonical role of glatiramer acetate to serve as a nucleic acid delivery scaffold that potentiates the safety of CpG adjuvant for cancer immunotherapy. Citation Format: Huan Gong, Daniel J. Griffin, Chad E. Groer, Xiaoqing Wu, Moustafa M. Abdelaziz, Sa Wu, Liang Xu, Laird M. Forrest, Cory J. Berkland. Glatiramer acetate enhances tumor retention and mitigates systemic toxicity of toll-like receptor 9 agonists as intratumoral immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3185.

Abstract 3188: Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics

Abstract A novel, injectable chitosan-glycerol hydrogel was developed and characterized. Upon injection with co-formulated therapeutics, the gel vastly improved molecule retention at the injection site, as compared to molecule delivery in less viscous media. Methods. The hydrogel was formed through a centrifugation process. 70% deacetylated, medium viscosity chitosan was dissolved in 0.1M HCl. Glycerol was then added, followed by vortexing. Next, 1x PBS and 1M NaOH were added to neutralize the mixture, which induced gelation. After hydrogel centrifugation at 10,000 rpm for 5 minutes, a hydrogel was separated from precipitate. Several formulation parameters were tested, including chitosan:glycerol volume ratio, chitosan concentration, chitosan degree of deacetylation, and chitosan molecular weight. The retention of model therapeutics, formulated in hydrogel or saline vehicles, following injection in agar-based tumor phantoms was quantified via absorbance and fluorescence readings. To assess biocompatibility, a non-contact cell viability assay was performed utilizing 3T3 fibroblasts seeded in the bottom of transmembrane wells with hydrogels added to the upper chamber. After 48 hours, cells were collected and counted utilizing trypan blue. New Data. A hydrogel for intratumoral therapeutic delivery was constructed with several desirable qualities, including biocompatibility and injectability through a 25-gauge needle. Different relative glycerol to chitosan volumes, from 5 to 95 w/v % glycerol, were tested to determine a range of gelation conditions. Glycerol volume most significantly impacted gelation conditions independent of chitosan concentration, with gelation occurring between 70-85% relative volume glycerol. Increasing chitosan solution concentration and chitosan molecular weight increased the range of chitosan:glycerol ratios resulting in gelation. The hydrogel improved load retention at the agar tumor phantom injection site for various sizes of model therapeutics compared to less viscous solutions. Cytotoxicity testing of the hydrogel showed a statistically insignificant difference between the live:dead cell ratios of the experimental and negative control groups. Conclusion. An injectable, biocompatible hydrogel was created through the neutralization and centrifugation of a chitosan-glycerol solution. The hydrogel displays physiological pH, injectability through a 25-gauge needle, biocompatibility, and vastly improved therapeutic load retention at the injection site compared to less-viscous delivery media. Chitosan-glycerol hydrogels may be useful for intratumoral delivery and retention of immunomodulators within the tumor microenvironment. Citation Format: Robert L. Kobrin, Siena M. Mantooth, David A. Zaharoff. Chitosan-glycerol injectable gel for intratumoral retention of immunotherapeutics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3188.

Efficacy and Safety of Triamcinolone Acetonide Injections Following Rhinoplasty: A Systematic Review of Recommended Doses, Complications, and Outcomes.

Triamcinolone acetonide injections (TAIs) have been suggested to decrease complications following rhinoplasty. This systematic review aimed to assess the efficacy and safety of TAIs following rhinoplasty. We performed a systematic literature search on Medline, Embase, Google Scholar, and Cochrane Central Register of Controlled Trials from inception to May 2023, without any timeframe limitations. The following terms were used: (Triamcinolone OR steroid injections OR triamcinolone acetonide) AND (Skin thickness OR supratip edema OR supratip deformity OR Pollybeak deformity) AND (rhinoplasty OR external rhinoplasty). We included randomized controlled trials and observational studies (prospective, retrospective, and case series). In total, six of the 1604 articles met our inclusion criteria. A total of 1524 patients were included in this study. Our results included patient demographics, type of rhinoplasty, post-injection follow-up period, site of injection, type of syringe used, timing of the first dose, volume and concentration used, time interval between doses, response to the injection, and complications of injection. To our knowledge, this is the first systematic review to address this issue. Our results demonstrate the ease and safety of TAIs as a first-line treatment, with positive outcomes and limited complications. TAIs can be used early postoperatively to minimize the need for revision surgery. Despite the limited number of studies on TAIs, this study provides the best available evidence that can help surgeons decide when to use the injection, the intervals between doses, and the duration of use. Further randomized controlled trials are required to confirm our findings. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Abstract 3392: Generation and characterization of transgenic oncopig model for lung cancer

Abstract Lung cancer (LC) is the leading cause of cancer-associated death in the United States. Preclinical findings in small animal models do not translate into human clinics. There is an urgent need to develop relevant preclinical large animal models for LC. We describe a novel method to induce LC in transgenic pigs carrying Cre-inducible KrasG12D and TrP53R167H mutations (Oncopigs). The Oncopigs (n=12; 9 females, and 3 males) at 9 weeks of age were anesthetized and adenovirus (1 × 1011 PFU) carrying Cre recombinase gene (Ad-Cre) ± polybrene (1:100) ± IL-8 (5 ng/ml) was injected via flexible bronchoscopy with two techniques: (1) Bronchial lavage (n=6) and (2) Transbronchial needle injection (n=6) into different lung lobes. As controls, a combination of polybrene ± IL-8 was injected without AdCre into the contralateral lobes in the same pigs (n=8). Oncopigs were monitored via clinical monitoring, blood counts, basic metabolic panel, and contrast-enhanced computed tomography (CT) imaging for LC progression and metastasis at 3-, 4-, 7-, 10-, 16-, and 26 weeks post-intervention. All animals tolerated the injections with expected weight gains. Blood counts and metabolic panels remained normal during LC progression. At the site of injection/lavage, lung masses were detected on CT imaging at 3 weeks post-injections. However, a decrease in masses was observed on CT at 7 weeks post-intervention. The decrease in size of the lung masses coincided with increasing attenuation. No distant metastases were observed on CT imaging. Lavage-based lesions appeared to be more heterogeneous with surrounding inflammatory changes. Transbronchial-injection-based lesions appeared more consolidated and coin-shaped without surrounding inflammatory changes. Control injection sites did not show any mass growth on CT imaging. Immunohistochemistry analysis on lung tumors revealed increased pancytokeratin, trichrome, E-cad, Ki-67, IBA, and CD3 expression. Further, immunofluorescence revealed decreased E-Cad, CK-19, and Zo-1 expression, whereas increased expression of N-Cad, FN1, snail, CD44, α-SMA, and γ-catenin, was observed in the LC and metastatic tissue compared to normal. We successfully generated and characterized a novel transgenic Oncopig LC model. There is robust tumor production status post AdCre delivery. One of four Oncopigs had carcinomatous metastatic skin growth. The remaining 7 Oncopigs are monitored longitudinally for tumor growth and development of metastasis. Citation Format: Kirtan Joshi, Nagabhishek Sirpu, Amanda Schmelzle, Ravikanth Poonooru, Benjamin Nelson, Pradeep Subramanyam, Colleen Garrett, Mariana Sponchiado, Sarah Schlink, Samantha Gerb, Jesse Porter, Dae Kim, Jeffrey Kunin, Jeffrey Bryan, Timothy Hoffman, Bhanu Telugu, Jussuf Kaifi, Satyanarayana Rachagani. Generation and characterization of transgenic oncopig model for lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3392.

Abstract 1191: Personalized neoantigen DNA vaccine GNOS-PV02 and pembrolizumab as second-line treatment for advanced hepatocellular carcinoma

Abstract Background: PD-1 inhibitors have modest efficacy as monotherapy in hepatocellular carcinoma (HCC). A personalized therapeutic cancer vaccine (PTCV) tailored against neoantigens identified in an individual’s tumor may enhance responses to PD-1 inhibitors through the induction of tumor-specific immunity. Here, we present results from a single-arm Phase Ib/2a trial evaluating a DNA plasmid (GNOS-PV02) encoding up to 40 neoantigens co-administered with plasmid-encoded IL-12 (pIL12) in combination with pembrolizumab (PEMBRO) in patients (pts) with advanced HCC.Methods: Pts were eligible for study therapy upon progression or intolerance with a 1L tyrosine kinase inhibitor (TKI). The PTCV [GNOS-PV02 (1mg) and pIL12 (0.34mg)] was administered intradermally via in vivo electroporation Q3w x 4 doses, and Q9w thereafter. PEMBRO was administered at 200mg IV Q3w. The primary endpoints were safety and immunogenicity. To evaluate the secondary endpoint of ORR per RECIST 1.1 by investigator review with a null hypothesis of an ORR of 16.9% (KN-240, Finn et al ASCO 2019), 36 pts were included to provide 80% power to reject the null hypothesis at the one-sided 0.10 level, assuming the true ORR rate of 33.1%. The data cut date was August 18, 2023.Results: Among the 36 enrolled pts who received at least one dose of treatment, there were no DLTs or treatment-related grade ≥3 events. The most common treatment-related adverse events were injection site reactions, observed in 41.6% of pts. ORR (mITT) per RECIST 1.1 was 30.6% (11/36; 9 confirmed and 2 unconfirmed) with 8.3% (3/36) of pts achieving a CR. This achieved statistical significance with a one-sided p-value = 0.031 (1-sided 90% CI 20.4%-100%) The mOS was 19.9 months. ctDNA changes correlated with radiographic responses and preceded them. A complete molecular response (100% ctDNA clearance) was detected in 7 pts including the 3 radiographic CRs, and 4 additional pts who continue to show durable tumor control (3PR, 1 SD). Immunological analyses confirmed the induction of neoantigen-specific T cell responses by IFNγ-ELISpot in 19/22 (86.4%) evaluable pts, and pts with a larger ELISpot response showed a trend towards longer OS. Multi-parametric cellular profiling and single-cell analysis revealed active, proliferative, and cytolytic vaccine-specific CD4+ and CD8+ effector T cells in the blood of immunized pts. In 14/14 (100%) of pts with paired pre- and on-treatment blood and tumor biopsies, we identified by TCRβ bulk sequencing expanded T cell clones in the peripheral blood that also trafficked into the tumor. Conclusions: Our results show that a PTCV plus PEMBRO is well tolerated and has clinical activity in pts with advanced HCC, and support the PTCV mechanism of action based on the induction of anti-tumor T cells in peripheral blood and tumor. A confirmatory phase 3 clinical study assessing OS is planned. Citation Format: Mark Yarchoan, Edward J. Gane, Thomas U. Marron, Renzo Perales-Linares, Jian Yan, Neil Cooch, Daniel Shu, Elana J. Fertig, Luciane T. Kagohara, Gabor Bartha, Josette Northcott, John Lyle, Sarah Rochestie, Joann Peters, Jason Connor, Elizabeth Jaffee, Alfredo Perales-Puchalt, David B. Weiner, Ildiko Csiki, Niranjan Y. Sardesai. Personalized neoantigen DNA vaccine GNOS-PV02 and pembrolizumab as second-line treatment for advanced hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1191.

Abstract 5005: Safety and tolerability of multi-epitope HER2 peptide vaccines in combination with trastuzumab emtansine in HER2-positive breast cancer patients with residual disease after neoadjuvant chemotherapy

Abstract Background: Residual disease after neoadjuvant chemotherapy (NAC) in breast cancer (BC) confers poor outcomes. Trastuzumab emtansine (T-DM1) is approved for HER2+ patients with residual disease after NAC. However, many patients still develop recurrence. H2NVAC is a multi-epitope CD4 helper T cell activating vaccine that includes a pool of 4 degenerate HER2-derived HLA-DR epitopes admixed with GM-CSF. Our previous phase I trial showed that this vaccine was safe and generated robust, long-lasting T and B cell immune responses. Method: We conducted a safety run-in phase of H2NVAC in combination with T-DM1 in stage II-III HER2+ BC with residual disease after NAC. Patients were treated with H2NVAC and T-DM1 for 6 cycles, followed by 2 boosters at 3 and 12 months. Dose-limiting toxicity (DLT) was defined as any grade (G) ≥ 3 toxicity occurring within 21 days after the first vaccination. Results: 20 patients were enrolled (median age 51; 27-69 years), including 80% White and 15% Black. 90% had hormone receptor-positive disease. There was no DLT observed in the safety run-in cohort. All adverse events (AEs) during the DLT period were grades 1 and 2, with fatigue being the most common (60% G1, 5% G2), followed by peripheral sensory neuropathy (55% G1, 5% G2), and injection site reaction (50% G1). Across all treatment cycles, the 10 most common AEs that were at least possibly related to treatment in all cycles are summarized in the table below. The injection site reaction was the most common AE, with 85% G1 and 15% G2. Conclusion: H2NVAC, in combination with T-DM1, was safe, with a favorable side effect profile. There was no DLT observed. The most common AE was injection site reaction, with the majority being G1. A multicenter, randomized, placebo-controlled, phase II trial of H2NVAC vs. placebo in combination with trastuzumab emtansine is currently ongoing through the ACCRU consortium (NCT04197687). Adverse Events Grades 1 2 N % N % Injection site reaction 17 85.0 3 15.0 Aspartate aminotransferase increase 13 65.0 Alanine aminotransferase increase 9 45.0 Fatigue 7 35.0 2 10.0 Peripheral sensory neuropathy 7 35.0 2 10.0 Alkaline phosphatase increase 8 40.0 Nausea 7 35.0 1 5.0 Arthralgia 7 35.0 Myalgia 5 25.0 1 5.0 Platelet count decrease 6 30.0 Citation Format: Saranya Chumsri, Sharmila Giri, Andy J. Ness, David W. Hillman, Nadine Norton, Davitte Cogen, Brian M. Necela, Aziza Nassar, Donald W. Northfelt, Pooja Advani, Rohit Rao, Kostandinos Sideras, Alvaro Moreno-Aspitia, Brenda J. Ernst, Kathryn J. Ruddy, Matthew P. Goetz, Keith L. Knutson. Safety and tolerability of multi-epitope HER2 peptide vaccines in combination with trastuzumab emtansine in HER2-positive breast cancer patients with residual disease after neoadjuvant chemotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5005.

Superparamagnetic iron oxide nanoparticle enhanced percutaneous microwave ablation: Ex-vivo characterization using magnetic resonance thermometry.

Percutaneous microwave ablation (pMWA) is a minimally invasive procedure that uses a microwave antenna placed at the tip of a needle to induce lethal tissue heating. It can treat cancer and other diseases with lower morbidity than conventional surgery, but one major limitation is the lack of control over the heating region around the ablation needle. Superparamagnetic iron oxide nanoparticles have the potential to enhance and control pMWA heating due to their ability to absorb microwave energy and their ease of local delivery. The purpose of this study is to experimentally quantify the capabilities of FDA-approved superparamagnetic iron oxide Feraheme nanoparticles (FHNPs) to enhance and control pMWA heating. This study aims to determine the effectiveness of locally injected FHNPs in increasing the maximum temperature during pMWA and to investigate the ability of FHNPs to create a controlled ablation zone around the pMWA needle. PMWA was performed using a clinical ablation system at 915MHz in ex-vivo porcine liver tissues. Prior to ablation, 50uL 5mg/mL FHNP injections were made on one side of the pMWA needle via a 23-gauge needle. Local temperatures at the FHNP injection site were directly compared to equidistant control sites without FHNP. First, temperatures were compared using directly inserted thermocouples. Next, temperatures were measured non-invasively using magnetic resonance thermometry (MRT), which enabled comprehensive four-dimensional (volumetric and temporal) assessment of heating effects relative to nanoparticle distribution, which was quantified using dual-echo ultrashort echo time (UTE) subtraction MR imaging. Maximum heating within FHNP-exposed tissues versus control tissues were compared at multiple pMWA energy delivery settings. The ability to generate a controlled asymmetric ablation zone using multiple FHNP injections was also tested. Finally, intra-procedural MRT-derived heat maps were correlated with gold standard gross pathology using Dice similarity analysis. Maximum temperatures at the FHNP injection site were significantly higher than control (without FHNP) sites when measured using direct thermocouples (93.1±6.0°C vs. 57.2±8.1°C, p=0.002) and using non-invasive MRT (115.6±13.4°C vs. 49.0±10.6°C, p=0.02). Temperature difference between FHNP-exposed and control sites correlated with total energy deposition: 66.6±17.6°C, 58.1±8.5°C, and 20.8±9.2°C at high (17.5±2.2kJ), medium (13.6±1.8kJ), and low (8.8±1.1kJ) energies, respectively (all pairwise p<0.05). Each FHNP injection resulted in a nanoparticle distribution within 0.9±0.2cm radially of the injection site and a local lethal heating zone confined to within 1.1±0.4cm radially of the injection epicenter. Multiple injections enabled a controllable, asymmetric ablation zone to be generated around the ablation needle, with maximal ablation radius on the FHNP injection side of 1.6±0.2cm compared to 0.7±0.2cm on the non-FHNP side (p=0.02). MRT intra-procedural predicted ablation zone correlated strongly with post procedure gold-standard gross pathology assessment (Dice similarity 0.9). Locally injected FHNPs significantly enhanced pMWA heating in liver tissues, and were able to control the ablation zone shape around a pMWA needle. MRI and MRT allowed volumetric real-time visualization of both FHNP distribution and FHNP-enhanced pMWA heating that was useful for intra-procedural monitoring. This work strongly supports further development of a FHNP-enhanced pMWA paradigm; as all individual components of this approach are approved for patient use, there is low barrier for clinical translation.

No immunological interference or concerns about safety when seasonal quadrivalent influenza vaccine is co-administered with a COVID-19 mRNA-1273 booster vaccine in adults: A randomized trial

ABSTRACT The objective of the study was to assess the safety and immunogenicity of mRNA-1273 COVID-19 booster vaccination when co-administered with an egg-based standard dose seasonal quadrivalent influenza vaccine (QIV). This was a phase 3, randomized, open-label study. Eligible adults aged ≥ 18 years were randomly assigned (1:1) to receive mRNA-1273 (50 µg) booster vaccination and QIV 2 weeks apart (Seq group) or concomitantly (Coad group). Primary objectives were non-inferiority of haemagglutinin inhibition (HI) and anti-Spike protein antibody responses in the Coad compared to Seq group. 497/498 participants were randomized and vaccinated in the Seq/Coad groups, respectively. The adjusted geometric mean titer/concentration ratios (95% confidence intervals) (Seq/Coad) for HI antibodies were 1.02 (0.89–1.18) for A/H1N1, 0.93 (0.82–1.05) for A/H3N2, 1.00 (0.89–1.14] for B/Victoria, and 1.04 (0.93–1.17) for B/Yamagata; and 0.98 (0.84–1.13) for anti-Spike antibodies, thus meeting the protocol-specified non-inferiority criteria. The most frequently reported adverse events in both groups were pain at the injection site and myalgia. The 2 groups were similar in terms of the overall frequency, intensity, and duration of adverse events. In conclusion, co-administration of mRNA-1273 booster vaccine with QIV in adults was immunologically non-inferior to sequential administration. Safety and reactogenicity profiles were similar in both groups (clinicaltrials.gov NCT05047770).

Fluoroscopic Guided Lumbar Erector Spinae (ESP) Field Blocks: A New Technique and Radiographic Analysis

IntroductionLumbar Erector Spinae (ESP) field blocks have become a common postoperative treatment for surgical pain. The use of long-acting medications like liposomal bupivacaine (Exparel) has become a major component of multi-modal postsurgical pain control. Traditionally ESP injections have been performed using ultrasound (U/S) guidance by an anesthesiologist. Spine surgeons have begun to utilize these liposomal injections in their procedures for post-operative pain management. Our study describes a fluoroscopic guided ESP field block technique which provides reproducible muscular coverage and pain control for spine surgery. Material and MethodsSixty patients undergoing single level lumbar fusion were treated preoperatively with bilateral fluoroscopically guided lumbar erector spinae ESP field blocks with liposomal bupivacaine. We looked at two different injection locations involving the ESP or multifidus muscle fascial planes. The injections contained Iohexal, which was used to evaluate the coverage area of the injection. The levels of coverage were recorded, and post-operative pain control was measured immediately, postoperatively, and at 24 hours. ResultsFluoroscopic field blocks at the L3-4 level were found to provide at least four levels of vertebral coverage rostral-caudally in both ESP and MF fascial planes. Pain was well controlled in both injection sites. ConclusionSurgeon-administered fluoroscopic guided ESP field blocks provided a reliable and consistent pattern of coverage with good postoperative pain control. This technique can be easily adopted by spine surgeons.

A randomized, blind, parallel controlled phase I clinical trial to evaluate the safety and preliminary immunogenicity of 23-valent pneumococcal polysaccharide vaccine in healthy people aged 2 years and older

BackgroundDespite some progress in pneumococcal immunization, the global burden of pneumococcal infection remains high, and pneumococcal disease remains a public health concern. Studies in China and abroad have found that 23-valent pneumococcal polysaccharide vaccine (PPV23) vaccination can effectively prevent invasive pneumococcal disease. This phase Ⅰ clinical study assessed the safety and immunogenicity of a PPV23 vaccine candidate. MethodsAll subjects were randomly assigned to receive one dose intramuscular injection of experimental vaccine or control vaccine at a ratio of 1:1. The incidence of any adverse events was observed within 30 min, 0–7 days and 8–28 days post vaccination and the incidence of abnormal blood biochemical and blood routine indicators were tested on the 4th day post vaccination, the incidence of serious adverse events (SAEs) at 6 months post vaccination was recorded. Blood samples were collected prior to vaccination and on the 28th day post vaccination, and serum antibodies were detected by enzyme linked immunosorbent assay (ELISA). ResultsThe most common adverse reaction was pain at the injection site, followed by erythema. There was no significant difference of the incidence of systemic adverse reactions between the two vaccine groups. The adverse reactions observed in the trial were all common vaccination-related reactions, and no serious adverse reactions were observed. Compared to pre-vaccination, the (geometric mean concentrations) GMCs of IgG (immunoglobulin G) specific antibody against each serotype were all increased in the experimental group and the control group, there were statistical differences in seroconversion rates of serotypes 4 and 20 between the two vaccine groups. ConclusionThis clinical study showed good safety of the PPV23 vaccine candidate produced by Ab&b Biotechnology Co., Ltd.JS had good safety after vaccination in people aged 2 years and older. At the same time, good immunogenicity was also demonstrated.

Accuracy of sentinel node mapping in Marjolin ulcer: Comparison of three different injection techniques

BackgroundMarjolin ulcer is a specific type of squamous cell cancer that can benefit from the use of lymphoscintigraphy.The purpose of this study was to evaluate 3 different injection techniques for sentinel node biopsy in patients with Marjolin ulcer. MethodsForty-eight patients with Marjolin ulcer (27 male and 21 female) ranging in age from 24 to 85 years were included in our study. Intratumoral (IT), peritumoral (PT) and periscar (PS) tissue injections of radiotracer were done in 9, 10, and 29 patients respectively. Injections were done 2–4 h before surgery. Lymphoscintigraphy was done for mapping the lymphatic drainage. During surgery, lymphatic mapping and sentinel node biopsy was performed using a handheld gamma probe. After harvesting sentinel nodes, regional lymph node dissection was done. ResultSentinel node detection rate was higher in the PS group as compared to the IT and PT groups (89.6% vs. 50% and 22.2%) respectively. False negative rate was 0%. Pathologically involved sentinel nodes were detected in 16% of the included patients of our study which led to management change. None of the patients with pathologically non-involved sentinel nodes developed regional lymph node recurrence. ConclusionLymphatic mapping and sentinel node biopsy is feasible in Marjolin ulcer with high detection rate and low false negative cases which by detection of regional lymph node involvement can potentially change the management of patients. Injection site may be an important factor influencing the success of the procedure and injection of the mapping material in the peri-scar normal skin proximal to the lesion is the best technique.

A novel hybrid BonT-A and hyaluronic acid cannula-based technique for eyelid ptosis and periorbital rejuvenation.

Eyelid ptosis is characterized by an inferior displacement of the upper eyelid when the eye assumes its primary position. Besides its aesthetic implications, ptosis can also adversely affect visual acuity. This study aimed to evaluate the simultaneous administration of IncobotulinumtoxinA (IncoBonTA) and hyaluronic acid effect in eyelid ptosis and ocular rejuvenation. A novel, non-surgical technique for eyelid ptosis management involving IncoBonTA and hyaluronic acid the co-administration within a single syringe, and applied using a cannula. The dual action of IncoBonTA and hyaluronic acid in conjunction with the exact injection sites approaches improves overall aesthetic outcomes but also optimizes the restoration of eyelid functionality in palpebral ptosis. The functional balance achieved among the contributory muscles-primarily the orbicularis oculi (OO) and its antagonists, the frontal muscle and levator palpebrae superioris (LPS), yields to both, cosmetic and functional.

Botulinum Toxin Injections to Manage Sequelae of Peripheral Facial Palsy.

Long-standing facial palsy sequelae cause functional, aesthetic, and psychological problems in patients. Botulinum toxin is an effective way to manage them, but no standardized recommendations exist. Through this non-systematic review, we aimed to guide any practitioner willing to master the ins and outs of this activity. We reviewed the existing literature and completed, with our experience as a reference center, different strategies of botulinum toxin injections used in facial palsy patients, including history, physiopathology, facial analysis, dosages, injection sites, and techniques, as well as time intervals between injections. The reader will find all the theorical information needed to best guide injections according to the patient's complaint, which is the most important information to consider.

Effectiveness and safety of immune response to SARS‑CoV‑2 vaccine in patients with chronic kidney disease and dialysis: A systematic review and meta‑analysis.

The coronavirus disease 2019 (COVID-19) vaccination is the most effective way to prevent COVID-19. However, for chronic kidney disease patients on long-term dialysis, there is a lack of evidence regarding the efficacy and safety of the immune response to the vaccine. The present meta-analysis explores the efficacy and safety of COVID-19 vaccine in the immune response of patients with chronic kidney disease (CKD) undergoing dialysis. PubMed, Web of Science, Science Direct, and Cochrane Library databases were systematically searched from January 1, 2020, to December 31, 2022. Data analysis was performed using REVMAN 5.1s and Stata14 software. Baseline data and endpoint events were extracted, mainly including age, sex, dialysis vintage, body mass index (BMI), vaccine type and dose, history of COVID-19 infection, seropositivity rate, antibody titer, pain at injection site, headache and other safety events. The meta-analysis included 33 trials involving 81,348 patients. The immune efficacy of patients with CKD and dialysis was 80% (95 CI, 73-87%). The seropositivity rate of individuals without COVID-19 infection was 76.48% (3,824/5,000), while the seropositivity rate of individuals with COVID-19 infection was 80.82% (1,858/2,299). The standard mean difference of antibody titers in CKD and dialysis patients with or without COVID-19 infection was 27.73 (95% CI, -19.58-75.04). A total of nine studies reported the most common adverse events: Pain at the injection site, accounting for 18% (95 CI, 6-29%), followed by fatigue and headache, accounting for 8 (95 CI, 4-13%) and 6% (95 CI, 2-9%), respectively. COVID-19 vaccine benefitted patients with CKD undergoing dialysis with seropositivity rate ≥80%. Adverse events such as fatigue, headache, and pain at the injection site may occur after COVID-19 vaccination but the incidence is low.