Additional Treatment Research Articles

Parotid sialolithiasis - Long term follow-up analyzing surgical approaches.

Present follow-up data comparing transoral and transfacial parotid gland procedures for stone removal to offer insight addressing technical considerations and complications. Retrospective study of a consecutive series of surgical treatments for parotid sialolithiasis from 2013 to 2018 at an academic institution by one surgeon provided review of 16 transoral and 10 transfacial procedures supplemented by long-term follow-up through telephone or mail. Clinical and radiographic parameters, additional treatment, and persistence of symptoms were evaluated. Four of 10 patients treated with the transfacial approach had parotid-cutaneous fistulas addressed with transdermal scopolamine patches and pressure dressings (one also with intraductal steroid infusion) with closure at a median of 12.5 days. A fifth fistula failed to resolve at 23 days and was addressed with parotidectomy. All 8 patients who were contacted (median: 106 months) reported complete resolution of symptoms. None had facial weakness.Six of 16 patients treated by a transoral approach had persistent stone fragments at the conclusion of operation. Four of these 6 patients underwent subsequent procedures (two transoral, one transfacial, one parotidectomy). Among the 11 patients who responded to long-term follow-up (median: 107 months), one reported mild symptoms insufficient to request treatment. Larger stone size coupled with proximal location correlated with the conversion from transoral to include transfacial approach. Patients with retained stone remnants at the conclusion of transoral stone removal are more likely to require additional procedures that result in long-term favorable results. The transfacial approach to stone removal offers long-term favorable results following the common short-term complication of salivary fistula. OCEBM Level 4.

Effect of betahistine on pro-inflammatory cytokine expression in autoimmune inner ear disease and Meniere's disease patients.

Betahistine is a partial H1 receptor agonist and a potent H3 receptor antagonist commonly used for the treatment of MD and peripheral vertigo. The aim of this study was to investigate the impact of betahistine on the salt induced cytokine expression profiles of AIED and MD patients. Peripheral blood mononuclear cells (PBMCs) were obtained from 24 patients with autoimmune inner ear disease (AIED) or Meniere's disease (MD) during an acute exacerbation of hearing loss. These PBMCs were cultured with 80 mM NaCl or a combination of 80 mM NaCl and betahistine and IL-1β and IL-6 expression were measured by real time PCR and ELISA. In most patients, IL-1β expression in response to NaCl exceeded the unstimulated condition and this expression was abrogated by the addition of betahistine, which was statistically significant at p = .004. mRNA expression of IL-1β was not reduced when samples were treated with both salt and betahistine compared to samples treated with salt alone, inferring the mechanism of betahistine-mediated IL-1β suppression is post-translational. Similarly, IL-6 cellular release was augmented with salt exposure and reduced with co-culture of betahistine. Unlike IL-1 however, betahistine appeared to reduce IL-6 mRNA expression. We observe that betahistine abrogates salt-induced IL-1β expression, suggesting an additional treatment option for AIED and MD patients with inflammatory mediated disease. Level 4.

Flecainide to Prevent Atrial Arrhythmia after Patent Foramen Ovale Closure, the AFLOAT Study: A Randomized Clinical Trial.

The real incidence of atrial arrhythmia (AA) after patent foramen ovale (PFO) closure and whether this complication can be prevented remain unknown. This study assessed if flecainide is effective to prevent AA during the first 3 months after PFO closure, and if 6 months treatment by flecainide is more effective than 3 months to prevent AA after PFO closure. AFLOAT is a prospective, multicentre, randomized, open-label, superiority trial with a blind evaluation of all the endpoints (PROBE design). Patients were randomized in a 1:1:1 ratio after PFO closure to receive flecainide (150 mg once a day in a sustained-release (SR) dose) for 3 months, flecainide (150 mg od SR dose) for 6 months, or no additional treatment (standard-of-care) for 6 months. The primary endpoint was the percentage of patients with at least one episode AA (≥30s) recorded within 3 months after PFO closure on long-term monitoring with an insertable cardiac monitor (ICM). The secondary endpoint was the percentage of patients with at least one episode of AA (≥30s) recorded with ICM during the 3-6 months period after PFO closure. 186 patients were included (mean age 54 years, male 68.8%) and AA (≥30s) occurred in 53 (28.5%) patients during the 6-month follow-up; 86.8% of these AA events occurred in the first month after PFO closure. The primary outcome occurred in 33/123 (26.8%) and 16/63 (25.4%) patients receiving flecainide for at least 3 months or standard of care, respectively [Risk Difference (RD) 1.4%; 95% confidence interval (CI) -12.9% to 13.8%, NS]. The secondary endpoint occurred in 3/60 (5.0%), 4/63 (6.3%), and 5/63 (7.9%) patients receiving flecainide 6 months, 3 months or standard of care, respectively [RD -2.9%; 95% CI -12.7% to 6.9%, and RD -1.6%; 95% CI -11.8% to 8.6%, respectively]. In the first 6 months following successful PFO closure, AA (≥30s) occurred in 28.5% of cases, mostly in the first month after the procedure. Flecainide did not prevent AA after PFO closure.

Limestone reaction in sandy soil: Rate effects, limestone type, moisture regime, and time

AbstractAn experiment was conducted in the greenhouse facilities of Embrapa Maize and Sorghum to evaluate the limestone reaction in sandy soil based on rates, limestone type, effective calcium carbonate equivalent (ECCE), and moisture regime over time. A factorial design of 4 × 2 + 3 was adopted, consisting of four limestone rates with 76% ECCE (0, 1, 2, and 4 Mg ha−1), two irrigation types (daily and monthly, simulating constant and intermittent moisture regime), and three additional treatments (three rates of “filler” limestone—99% ECCE—under monthly irrigation). Soil chemical characteristics were analyzed at 1, 2, 3, 6, and 12 months after treatment application. Soil fertility improved at the first month after treatment application, with emphasis on higher limestone rates, monthly moisture regime, and filler lime stone. The highest limestone rate did not increase the pH above 7.0. The recommended limestone rate was insufficient to elevate Ca + Mg levels to the adequate level for current production genotypes and systems, which demand higher standards. These outcomes reinforce the need for carrying out further studies and potential revision in liming recommendations for sandy soils.

Molecular classification and adjuvant treatment in endometrioid endometrial cancer with microcystic elongated and fragmented (MELF) invasion pattern.

To assess the characteristics, molecular classification, and role of adjuvant treatment in patients with endometrioid endometrial cancer (EEC) and microcystic elongated and fragmented (MELF) myometrial invasion pattern. This study included patients who were diagnosed with EEC with a MELF invasion pattern and underwent surgery from January 2019 to December 2023. We analyzed molecular classification, clinicopathological characteristics, and prognostic outcomes, including recurrence and adjuvant therapy. Out of 529 patients, 84 (15.9%) exhibited the MELF pattern, with 1 (1.2%) classified as POLE-mutation, 19 (22.6%) as mismatch repair deficient, 53 (63.1%) as no specific molecular profile, and 11 (13.1%) as p53-mutant subtype. Fifty (59.5%) patients with MELF invasion pattern received adjuvant chemotherapy (CT) ± external beam radiation therapy (EBRT), 19 (22.6%) received EBRT only, and 15 (17.9%) received no adjuvant treatment. Receiving adjuvant therapy was significantly associated with the risk level defined by the ESMO guideline for endometrial cancer (p = 0.002). With a median follow-up of 26 months (range: 1-59), the progression-free survival at 3-years for the MELF invasion patients was 91%. Seven patients with the MELF pattern experienced recurrence, of whom one was in stage IA (low risk, local recurrence) and did not receive any additional treatment, two were in stage IB (intermediate / high-intermediate risk, distant recurrence) and received EBRT only and the remaining four were in stage III to IV and had distant recurrence despite receiving adjuvant chemotherapy with or without EBRT. Among 43 intermediate- and high-intermediate-risk EEC patients, receiving CT ± EBRT was significantly associated with better DFS than without CT (p = 0.047). The presence of the MELF pattern in EEC should be incorporated into decision-making regarding adjuvant therapy. The use of adjuvant treatment should be tailored based on histology and molecular type.

The evidence for probiotics in the treatment of digestive disorders in the pediatric population.

Health claims for many probiotic-labeled products are poorly substantiated. This technical review addressed the clinical question: "Do probiotics have a role in the management of the following conditions in childhood?" Evidence supports efficacy for probiotic strains of Saccharomyces boulardii, Lactobacillus reuteri, and Lactobacillus rhamnosus GG for improving outcomes of acute gastroenteritis, of S. boulardii and L. rhamnosus GG for antibiotic-associated diarrhea, and of S. boulardii for Clostridium difficile diarrhea. For functional constipation and GERD, a role for probiotics is questionable as evidence of efficacy is either absent or marginal and as existing treatments are effective. For infantile colic and chronic abdominal pain, where existing treatments have limited efficacy and some important side effects, the use of probiotics, given their safety, is recommended, notwithstanding the evidence is low to moderate. While there is some evidence that probiotics could improve outcomes in the management of celiac disease, obesity, and, to a lesser extent, promotion of growth, their role is adjunctive as dietary management is fundamental. The evidence also supports an adjunctive role for probiotics in the treatment of Helicobacter pylori infection and ulcerative colitis. Decisions on probiotic prescription need to take into account disease tempo, severity, and burden, as well as probiotic strain and dose. Any potential advantage will have to be weighed against the complexity and costs of an additional treatment.

Characteristics of multiple esophageal squamous cell carcinomas detected in the surveillance after endoscopic resection.

Endoscopic resection (ER) of esophageal squamous cell carcinoma (ESCC) is an organ-preserving treatment; however, heterochronic carcinomas are often encountered. Most patients are treated using ER; however, for some, this is inadequate and requires additional treatment. We sought to identify the characteristics and frequency of lesions at high risk of metastasis during surveillance based on Lugol-voiding lesion (LVL) grading and esophagogastroduodenoscopy (EGD) intervals. Of the 1301 patients who underwent ER, 956 underwent surveillance EGD at our hospital for at least 1year (median, 59months). We analyzed identified multiple ESCCs to reveal the characteristic of high-metastasis-risk lesions, which was defined ESCC with submucosal or lymphovascular invasion. In the 956 patients, 444 multiple ESCCs were identified in 216 patients and the cumulative incidence of multiple ESCCs was 15.4% and 22.9% at 3 and 5years, respectively, while for high-risk lesions, it was 1.0% and 1.8%. The risk factors for high-metastasis-risk lesions were being female (odds ratio (OR):5.58, 95% confidence interval (CI):1.96-15.9), lesions located in the cervical/upper thoracic esophagus (OR: 4.81, 95% CI:1.80-12.8), and the presence of submucosal tumor (SMT)-like marginal elevation (OR:65.4, 95% CI:11.0-390). No significant differences in the frequency of high-risk lesions were found based on LVL grade at any EGD intervals. During endoscopic surveillance, attention should be given to the cervical/upper thoracic esophagus and lesions with SMT-like marginal elevation. The frequency of high-metastasis-risk lesions was not different by LVL grade or EGD intervals.

Effectiveness of PRP in Reduction of Localized Alveolitis in Young Adult Patients

ABSTRACT Background: Localized alveolitis, commonly known as dry socket, is a painful post-extraction complication that occurs when the blood clot at the site of the tooth extraction disintegrates. Platelet-rich plasma (PRP), an autologous concentration of platelets in plasma, has been proposed to enhance wound healing and reduce the incidence of alveolitis. Materials and Methods: This randomized controlled trial included 100 young adult patients aged 18-35 undergoing mandibular third molar extractions. The patients were randomly assigned to the PRP group (n = 50) or the control group (n = 50). In the PRP group, PRP was prepared from the patient’s blood and applied to the extraction site immediately after tooth removal. In the control group, no additional treatment was applied. The primary outcome was the incidence of localized alveolitis within 7 days post-extraction. Secondary outcomes included pain levels assessed using a visual analog scale (VAS) and wound healing evaluated clinically. Results: The incidence of localized alveolitis was significantly lower in the PRP group (6%) compared to the control group (20%) (P < 0.05). Patients in the PRP group reported lower pain scores on the VAS at 3 and 7 days post-extraction, with mean scores of 2.5 and 1.2, respectively, compared to 4.0 and 2.8 in the control group. Clinical evaluation showed enhanced wound healing in the PRP group, with fewer signs of inflammation and better epithelialization. Conclusion: The application of PRP significantly reduces the incidence of localized alveolitis and accelerates wound healing in young adult patients following mandibular third molar extractions. PRP is a promising adjunctive treatment that enhances postoperative recovery and patient comfort.

Complementary Superwetting Structures Treated by a Femtosecond Laser for Simultaneous Spontaneous Directional Transport of Water Droplets and Underwater Bubbles.

The control of fluid transport is crucial and has broad applications in the fields of intelligent systems and microfluidics. However, current studies usually focus on the spontaneous directional transport of a single type of fluid or require complex preparation processes. In this paper, the single femtosecond laser direct processing of complementary superwetting structures using polyimide/polytetrafluoroethylene is proposed, for the first time, to realize simultaneous spontaneous directional transport of water droplets and underwater bubbles without any additional energy or chemical treatment. The flexible laser fabrication enables the creation of diverse transport structures, facilitating the achievement of linear and curvilinear fluid transport on superwetting structures. In addition, relevant applications in self-transporting chemical reactions and bubble switching are presented. This technique provides a novel approach to fabricate patterned superwetting surfaces for applications in intelligent transport, microbiology, and chemistry.

EGS SO32 - Management of Spontaneous Oesophageal Perforations in the era of Endo-Vacuum Therapy- Preliminary Results of a Single-Institution Study

Abstract Background Spontaneous Oesophageal Perforation (SOP) is a rare gastro-intestinal surgical emergency with devastating morbidity and mortality. Given the rarity of the entity, there is no up-to-date evidence on outcomes in the context of centralized esophagogastric services neither consensus guidelines nor standardized treatment algorithms on how these should be optimally managed. Endoscopic Vacuum Therapy (EVT) has emerged as safe and effective option particularly in cases where major invasive surgery would otherwise be deferred. Herein, we sought to explore the effectiveness, patient benefit and related morbidity/mortality by exploring the strategy outcomes in SOPs prior to and during periods where EVT was available. Method A single-centre retrospective cohort study incorporating all consecutive patients (N=72) presented or transferred to our tertiary oesophagogastric unit for SOP management between 01/01/2009-31/12/2023 was undertaken. Patients with anastomotic leak post-surgery or perforation secondary to malignancy, iatrogenic, traumatic or food bolus were excluded. Primary study-outcomes were treatment type including non-operative, EVT after 01/01/2018 or other endoscopic therapy, surgical operation including laparotomy, thoracotomy, primary defect repair or over a T-tube, disconnection with oesophagostomy, stenting or other interventional radiology procedures and their rate of success or failure. Secondary outcomes were length of stay, 90-day complications requiring re-intervention or re-admission, 30-, 90-day, 1-year mortality. Results In 2009-2017 pre-EVT period, 25/72 patients were managed a) 18/25 surgically with thoracotomy and T-tube, b) non-surgical 7/25, four were palliated. 30-day, 90-day mortality were 4/25 and 2/25, 90-day morbidity Clavien-Dindo >IIIa 14/25 (56%), 90-day reintervention 8/25 (32%), median LOS 27 days. In 2018-2023 EVT period , 47/72 patients were treated with a) laparotomy, left thoracotomy, defect repair over t-tube, chest drainage in 18/47, b) non-surgical 15/47, c) endoscopy 6/47, d) EVT in 14/47. 30-day mortality was 6/47, 90-day mortality 2/47, 90-day morbidity Clavien-Dindo >IIIa 32/47 (68%), 90-day reintervention 26/47 (55.3%), median LOS 34 days. 1-year mortality was 5/25 and 3/47 respectively. Conclusion EVT therapy appears to be a feasible additional treatment modality in the management of spontaneous oesophageal perforations. Optimal patient selection, therapeutic endoscopic expertise, knowledge of the technique, multidisciplinary approach and team collaboration are essentials for favourable outcomes. Of note, management of oesophageal perforations in a dedicated UGI centre is directly related to patient outcomes and is recommended as soon as such a diagnosis is confirmed.

EGS SO30 - Management of Iatrogenic Oesophageal Perforations in the era of Endo-Vacuum Therapy- Preliminary Results of a Single-Institution Study

Abstract Background Iatrogenic oesophageal perforation (IOP) following diagnostic and therapeutic interventions at the oesophagus or adjacent organs are responsible for nearly half of oesophageal perforations. If not recognised within 24 hours of injury, then they are associated with devastating morbidity and mortality. Available treatment options encompass non-operative for early perforation without sepsis, endoscopic with endoclip/stent and surgical including primary repair, exclusion and diversion or oesophagectomy. Recently, Endoscopic Vacuum Therapy (EVT) has been introduced as safe and effective alternative approach. We sought to assess treatment outcomes in patients with IOPs prior to and during periods where EVT was available as treatment option. Method A single-centre retrospective cohort study incorporating all consecutive patients (N=30) presented or transferred to our tertiary oesophagogastric unit for IOP management between 01/01/2009-31/12/2023 was undertaken. Patients with anastomotic leak post-surgery or spontaneous perforation secondary to malignancy or benign pathology were excluded. Primary study-outcomes were treatment type including non-operative, EVT after 01/01/2018 or other endoscopic therapy, surgical operation including laparotomy, thoracotomy, primary defect repair or over a T-tube, disconnection with oesophagostomy, stenting or other interventional radiology procedures and their rate of success or failure. Secondary outcomes were length of stay, 90-day complications requiring re-intervention or re-admission, 30-, 90-day and 1-year mortality. Results In 2009-2017 pre-EVT period, 11/30 patients were managed a) non-surgically 7/11, b) endoclip 3/11 and stenting 1/11. 30-day and 90-day mortality were 1/11, 90-day morbidity Clavien-Dindo >IIIa 3/11 (27.3%), 90-day reintervention 8/11 (72.7%), median LOS 27 days. In 2018-2023 EVT period, 19/30 patients were treated with a) laparotomy, left thoracotomy, defect repair over t-tube, chest drainage in 5/19, b) non-surgical 7/19, c) IR NJT, stent or PEG in 6/19 d) EVT in 4/19. 30-day mortality was 0/19, 90-day mortality 1/19 (5.2%), 90-day morbidity Clavien-Dindo >IIIa 7/19 (36.8%), 90-day reintervention 9/19 (47.4%), median LOS 61 days. 1-year mortality was 0/19 for both. Conclusion EVT therapy appears to be a feasible additional treatment modality in the management of iatrogenic oesophageal perforations. Careful patient selection, therapeutic endoscopic expertise, knowledge of the technique, multidisciplinary approach and team collaboration are essentials for favourable outcomes. Of note, management of oesophageal perforations in a dedicated UGI centre is directly related to patient outcomes and is a sine qua non.

Comparative Analysis of Sewage Sludge Characteristics After Natural Deposition, Accelerated Aging, and Composting

This study investigated treatment methods for urban wastewater sludge, specifically examining natural drying over five years, accelerated freeze–thaw–drying cycles, and composting with and without a zeolite additive. The findings reveal that composting effectively stabilized the sludge while retaining essential nutrients crucial for agriculture. Notably, with the addition of 2% zeolite by total mass, approximately 40% of the total nitrogen was preserved. Adequate aeration during composting maintained acceptable levels of phosphorus compounds, with the phosphorus content expressed as P2O5 showing significant retention compared with the natural drying methods. Composting also demonstrated a substantial reduction in petroleum hydrocarbon concentrations, which decreased from 30 mg/kg to 3 mg/kg, thereby showcasing its potential for processing contaminated sludge. The inclusion of zeolite enhanced the nitrogen retention by an additional 10–20% compared with the composting without zeolite, aligning with previous studies on its effectiveness. While composting and thermal treatments, like accelerated freeze–thaw cycles, influenced the physical properties of the sludge—such as reducing the moisture content and altering the volatile substance concentrations—they did not significantly affect the heavy metal levels. Natural drying over five years resulted in reduced metal quantities, which possibly reflected changes in the wastewater characteristics over time. Given that the heavy metal concentrations remained largely unchanged, additional treatment methods are recommended when the initial sludge contains high levels of these contaminants to ensure the safe use of the final product as fertilizer. This study underscored the significant role of biochemical and microbiological processes during composting and natural drying in transforming sludge properties. Future research should focus on establishing upper contamination thresholds and exploring microbiological safety measures to enhance the viability of sludge reuse in agriculture, balancing nutrient preservation with environmental safety.

Energy Band Alignment and Defect Synergistic Regulation Enable Air-Solution-Processed Kesterite Solar Cells With the Lowest VOC Deficit.

The major challenge in preparing high-performance Cu2ZnSn(S,Se)4 solar cells is the large open circuit voltage deficit (VOC-def). A new strategy utilizing the synergistic substitution of Ag and In dual cations has been proposed to simultaneously address the problems of undesirable interface band alignment and high-density detrimental bulk defects, obtaining decreased carrier recombination rate and increased minority carrier lifetime. The shorter In-S/Se bonds move the CBM higher by generating stronger repulsive force than the Sn-S/Se bonds, thus adjusting the interface band alignment. Ag substitution can effectively suppress Cu─Zn disorder, while Ag, In dual substitution can further passivate Sn-related defects and solve the issue of low carrier concentration in Ag single-substituted samples. Besides, the superior carrier property of In-Se materials significantly enhanced the device carrier lifetime and minority carrier diffusion length. The state-of-the-art air-solution-processed CZTSSe device without any addition treatment with 14.33% efficiency and 580mV VOC is obtained, possessing the lowest VOC-def value currently available in the CZTSSe field (VOC/VOC SQ = 64.7%). This work emphasizes the synergistic modulation of band alignment, defect level, grain growth, and carrier transportation by dual cation substitution, which paves a convenient and effective way to realize high-performance solar cells and photovoltaic devices.

Abstract 4137339: Application of PLGA-PEG-PLGA Thermosensitive Hydrogel Loaded with Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Ginsenoside Rb3 in the Treatment of Acute Myocardial Infarction

Background: Ginsenoside Rb3 (GSRb3) is a traditional Chinese medicine monomer. We aim to investigate the effects of GSRb3 on the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and the reparative effects of PLGA-PEG-PLGA thermosensitive hydrogel loaded with hiPSC-CMs and GSRb3 (NP GSRb3 @Gel+iCM) on myocardial infarction (MI). Methods: 1. Western Blot, RT-qPCR, cell immunofluorescence staining, and CCK-8 assays were employed to assess the proliferative effects of different concentrations of GSRb3 on neonatal mouse primary cardiomyocytes (NCMs) and hiPSC-CMs. 2. Transcriptomic gene sequencing technology was utilized to investigate the mRNA expression changes of hiPSC-CMs induced by GSRb3; The NP GSRb3 @Gel+iCM was injected into the left ventricular myocardium of the MI mice; the same volume injections of hiPSC-CMs (iCM group) and PLGA-PEG-PLGA thermosensitive hydrogel loaded with GSRb3 (NP GSRb3 @Gel group) served as control; Additionally, MI model group without additional treatment and sham group were established. 3. At 4 weeks post-MI, echocardiography, Sirius Red/Fast Green staining and immunofluorescence staining were utilized to evaluate the heart function, infarction size and survival rate of transplanted hiPSC-CMs. Results: GSRb3 inhibit the apoptosis of NCMs while promote proliferation of NCMs and hiPSC-CMs significantly. After 4 weeks of treatment, the engraftment rate of hiPSC-CMs in NP GSRb3 @Gel+iCM group (36.7%) was 4.8 times that of iCM group (7.7%); Compared to the MI group, NP GSRb3 @Gel group and iCM group, NP GSRb3 @Gel+iCM group showed significant improvement in cardiac function; The myocardial repair effect in NP GSRb3 @Gel+iCM group was significantly superior to NP GSRb3 @Gel group and iCM group, with a 47% reduction in infarct size compared to MI group, and further reduction in left ventricular anterior wall thickness compared to NP GSRb3 @Gel group and iCM group. Conclusion: GSRb3 promotes the proliferation of hiPSC-CMs both in vitro and in vivo. NP GSRb3 @Gel+iCM significantly increase the engraftment of hiPSC-CMs, promote angiogenesis, reduce infarction size, inhibit left ventricular remodeling and improve cardiac function.

Effectiveness and safety of hydrogen inhalation therapy as an additional treatment for hypertension in real-world practice: a retrospective, observational study in China

AimTo evaluate the real-life effectiveness and safety of hydrogen inhalation (HI) therapy as an additional treatment in Chinese adults with hypertension.MethodsThis observational, retrospective clinical study included hypertensive patients receiving routine antihypertensives with or without HI initiation from 2018 to 2023. Participants were assigned to the HI group or non-HI group (control group) after propensity score matching. The changes in mean systolic blood pressure (SBP) level during the 24-week follow-up period in different groups were examined primarily. The secondary outcome was the changes in diastolic blood pressure (DBP) and blood pressure (BP) control rate during the study. Several subgroup and sensitivity analyses were performed to confirm the robustness of our main findings. Adverse event (AE) was also assessed in patients of both groups.ResultsIn total, we selected 2,364 patients into the analysis. Both mean SBP and DBP levels significantly decreased in the HI group compared to control group at each follow-up visit with the between group difference of −4.63 mm Hg (95% CI, −6.51 to −2.74) at week 8, −6.69 mm Hg (95% CI, −8.54 to −4.85) at week 16, −7.81 mm Hg (95% CI, −9.57 to −6.04) at week 24 for SBP, and −1.83 mm Hg (95% CI, −3.21 to −0.45) at week 8, −2.57 mm Hg (95% CI, −3.97 to −1.17) at week 16, −2.89 mm Hg (95% CI, −4.24 to −1.54) at week 24 for DBP. Patients in the HI group were more likely to attain controlled BP at the follow-up period with odds ratio of 1.44 (95% CI, 1.21–1.72) at week 8, 1.90 (95% CI, 1.59–2.27) at week 16, and 2.24 (95% CI, 1.87–2.68) at the end. The trends of subgroup and sensitivity analyses were mostly consistent with the main analysis. The incidences of AEs were similar between the HI group and control group with all p-value >0.05.ConclusionThe HI therapy is related to significant amelioration in BP levels with acceptable safety profile in Chinese hypertensive adults after 24 weeks of treatment, building a clinical ground for further research to evaluate the antihypertensive effect of HI therapy.

Abstract 4136627: Development of a biomarker to predict refractory cases in Kawasaki disease patients -towards the development of diagnostic kit-

Introduction: Kawasaki disease (KD), which is the most common multisystem vasculitis with unknown causes in childhood, causes coronary artery lesions (CALs). Treatment with a high dose of intravenous immunoglobulin (IVIG) is the most effective therapy for the acute phase of KD. However, some very severe cases need several additional treatments and are at risk for CALs. Several scoring systems that have tried to predict IVIG-resistant patients failed in multiethnic populations. Aims: To develop the most effective biomarker for predicting refractory cases and determine the cut-off value for the development of the diagnostic kit. Methods: Multicenter, prospective, observational study was conducted at 49 hospitals in Japan between September 2017 and December 2023. The subjects consisted of 1310 KD patients, including Group 1 (n=50); treatment-resistant cases that required additional treatment of 3rd line or more (defined as refractory cases), and Group 2 (n=1260); cases that completed the treatment with 1st or 2nd line. Tenascin C (TN-C), Pentraxin 3 (PTX3), and Procalcitonin (PCT) values, which were selected by systematic review and a pilot study, were measured before initial treatment in each group. The cut-off value of the biomarker, which had the highest area under the curve (AUC), was determined. Results: All three biomarker values were significantly higher in Group 1 than Group 2 (p<0.01). Median [Interquartile range] in Group 1 vs Group 2 and AUC were PTX3; 44.6 [32.3-67.9] vs 12.2 [6.9-26.9]ng/ml, AUC=0.83, PCT; 4.3 [1.9-7.8] vs 0.6 [0.2-1.9]ng/ml, AUC=0.81, TN-C; 182 [122-222] vs 123 [94-163]ng/ml, AUC=0.71. PTX3 showed the highest AUC with the cut-off value of 31.7ng/ml [95% confidence interval; 31.7-34.9]. Group 1 could be predicted by PTX3 with the sensitivity of 80%, the specificity of 82%, the positive predictive value of 13% and the negative predictive value of 99%. Conclusions: It may be possible to predict refractory KD cases with high sensitivity and specificity by PTX3 value before initial treatment, and possibly develop a diagnostic kit using PTX3 value for prediction of refractory cases.

Life After EBPs: Characterizing Subsequent Engagement in Evidence-Based Psychotherapy After Completion of an Initial Trauma-Focused EBP in a National Sample of VA Patients.

Many Veterans who complete prolonged exposure (PE) or cognitive processing therapy (CPT) report residual symptoms, but it is unclear how to best address the mental health needs of these individuals. Examining patterns of mental health service utilization following completion of these two treatments may provide insight into how to best serve this group of individuals. In a large cohort of Veterans (N = 12,514) who sought treatment in the Veterans Health Administration during Fiscal Years 2015-2019, logistic regression models were used to assess the odds of initiating an additional course of trauma-focused (i.e., PE or CPT) or depression-focused psychotherapy in the year following completion of PE or CPT based on demographic, psychiatric, and treatment effectiveness-related variables. Approximately 9% of Veterans engaged in either trauma-(6%) or depression-(3%) related psychotherapy in the year following discharge from PE or CPT. Factors associated with increased odds of trauma-focused treatment initiation included having a sleep disorder diagnosis (OR = 1.23), a substance use disorder diagnosis (OR = 1.27), or experiencing military sexual trauma (OR = 1.64). Factors associated with increased odds of depression-focused treatment initiation included having a depression diagnosis (OR = 2.02). This study suggests that certain subgroups of Veterans who engage in PE or CPT (e.g., Veterans with comorbid sleep or substance use problems) are more likely to seek additional evidence-based treatment and may require augmentations to maximize clinical benefits, either during the initial course of treatment or subsequent to PTSD treatment.

Abstract 4144560: Phase 2 Open-label, Single-arm, Multi-center Clinical Trial to Evaluate the Efficacy and Safety of Camostat Mesylate in Patients with Protein-losing Enteropathy after Fontan Operation-Preliminary Outcome

Introduction: Protein-losing enteropathy (PLE) is a multifaceted condition that profoundly affects the systemic health and quality of life of Fontan patients. Despite medical progress, the treatment of PLE remains a significant challenge. This study investigates the efficacy and safety of Camostat Mesylate for managing PLE patients who have undergone the Fontan operation. Hypothesis: We hypothesize that Camostat Mesylate will enhance the gut environment, resulting in increase of serum albumin levels and decrease of stool alpha-1 antitrypsin levels in PLE patients following Fontan operation. Methods: This phase 2, multicenter, open-label, single-arm trial included patients over 4 years old diagnosed with PLE following Fontan operation. Camostat Mesylate was added to conventional treatments, with follow-up assessments at 1, 3, and 6 months, and a final evaluation one month after discontinuation. Efficacy was measured by changes in serum albumin, stool alpha-1 antitrypsin levels, and PLE symptoms such as diarrhea, edema, weight changes, and ascites. Results: Nineteen patients were enrolled in the study, of whom fifteen patients completed follow-up as per protocol. The median age was 15 years (interquartile range, 12.0-21.3). The median time between the Fontan operation and PLE diagnosis was 2.4 years. Serum albumin levels increased from 2.5 to 2.6 g/dL (p=0.504), and stool alpha-1 antitrypsin levels decreased significantly from 280.0 to 172.1 mg/dL (p=0.033). Notably, patients with diarrhea at baseline showed substantial improvement in both parameters, with increased serum albumin levels from 1.8 to 2.2 g/dL and decreased stool alpha-1 antitrypsin levels from 220.3 to 80.2 mg/dL. No serious adverse events were reported during study period. Conclusions: Camostat Mesylate demonstrated safety and efficacy, reducing stool alpha-1 antitrypsin in PLE patients after Fontan operation, especially those with diarrhea at baseline. Therefore, Camostat Mesylate could be considered as an additional treatment option for patients with PLE following Fontan operation. Key words: Camostat mesylate; protein-losing enteropathy; Fontan operation Source of Funding: This research was funded by SNUH Lee Kun-hee Child Cancer&Rare Disease Project, Republic of Korea.

ANGI-12. THE IMPACT OF STANDARD-OF-CARE TREATMENT ON THE RELATIONSHIP BETWEEN CELL DENSITY AND SOX2 POSITIVITY IN GLIOBLASTOMA PATIENTS AT AUTOPSY

Abstract INTRODUCTION Sex-determining region Y-box 2 (SOX2) staining highlights pluripotent cells and provides an early sign of tumor cell invasion in glioblastoma patients. This infiltration can often occur at the single cell level and can occur in the absence of lower resolution histological tumor features such as hypercellularity. This study assessed the impact of standard treatment regimens on the relationship between cellularity and SOX2+% at death using autopsy samples as ground truth. METHODS A total of 36 IDH-wildtype glioblastoma patients were included for this study (23M/13F, mean age=61.9). Tissue samples from both suspected tumor invasion and suspected normal tissue were collected for each patient, which were then stained for SOX2, digitized at 40X resolution, and segmented into positive staining nuclei percentage using a color deconvolution algorithm. These samples were then aligned to the MRI using in-house MATLAB-based software, where manually defined control points placed on areas of architectural similarity are used to compute a transform that corrects for nonlinear shrinkage of the tissue sample due to post-mortem processing. The association between SOX2+% and cell density was then computed per subject, and compared between patients who received SOC (radiation and temozolomide) treatment following surgery (as well as additional treatment per case, n=31) and patients who opted for no additional treatment following surgery (n=5). RESULTS Patients who received no additional treatment showed substantially higher correlation between cell density and SOX2+% than patients who had received SOC (t=2.90, p=0.006). No association with overall survival was observed (r=0.17, p=0.329). CONCLUSIONS These results indicate a decoupling between hypercellularity and SOX2+% associated with standard GBM treatments, indicating that radiation and other treatments induce a more heterogenous tumor microenvironment that could lead to single-cell tumor invasion beyond gross histological markers of tumor presence.

Cost minimization analysis of treatments for metastatic HER2-positive breast cancer in Peru: Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injections.

The main objective of this study is to determine whether the employment of fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection (PH FDC SC; and Phesgo as brand name) to treat metastatic HER2-positive breast cancer patients would minimize costs compared to the traditional treatment of separate intravenous doses of pertuzumab and trastuzumab in Peru. To achieve this, we used EsSalud (the social security health insurance) data and assessed it through a mixed strategy, which consisted of a quantitative and a qualitative approach. The first one aimed to calculate the direct (non-drug consumables, drugs, and healthcare professionals) and indirect costs of both treatments to develop a comparison, whilst the second aimed to validate information and internalize the procedure in an EsSalud context. Overall, we found that the usage of PH FDC SC would be cost saving in EsSalud's context. Specifically, we found three main advantages. Firstly, PH FDC SC generates a savings of 62% in non-drug consumables, which helps alleviate the healthcare system budget constraint. Secondly, its adoption frees up 61 hours of treatment and observation time for a single patient per year, which in turn increases the attention capacity of the healthcare system in terms of nursing hours and chemotherapy couches. Thirdly, the reduction of clinic time supposes an advantage for the patient in the form of increased productivity and well-being. Hence, the adoption of this drug would improve the quality of life of patients while reducing costs and pressure on the healthcare system. This is aligned with the strategy of prioritizing the appropriate breast cancer treatment within the National Cancer Care Plan. In this regard, we also found that the savings produced from switching from the traditional intravenous treatment to the subcutaneous one would allow EsSalud to afford full annual costs of 2 additional treatments, but without increasing their budget. This would cover 7% of the gap of 29 patients who do not have access to full treatment.