Adjunctive Therapy Research Articles

Enhancing Radiofrequency Ablation for Hepatocellular Carcinoma: Nano-Epidrug Effects on Immune Modulation and Antigenicity Restoration.

Radiofrequency ablation (RFA), a critical therapy for hepatocellular carcinoma (HCC), carries a significant risk of recurrence and metastasis, particularly owing to mechanisms involving immune evasion and antigen downregulation via epigenetic modifications. This study introduces a "nano-epidrug" named MFMP. MFMP, which is composed of hollow mesoporous manganese dioxide (MnO2) nanoparticles, FIDAS-5 as an MAT2A inhibitor, macrophage membrane, and anti-PD-L1 (aPD-L1), targets HCC cells. By selectively binding to these cells, MFMP initially reverses immune suppression via PD-L1 inhibition. After endocytosis, MFMP disassembles in the tumor microenvironment, releasing FIDAS-5 and Mn2+. FIDAS-5 prevents cGAS methylation, whereas Mn2+ aids STING pathway restoration. In addition, FIDAS-5 reduces m6A RNA modification, suppressing EGFR expression. These changes enhance HCC antigenicity to promote cytotoxic T cell recognition and cytotoxic killing. Furthermore, MFMP mediates immunogenic cell death in HCC by synergizing with RFA through cGAS DNA demethylation, EGFR mRNA demethylation, and TBK1 protein phosphorylation, thereby inhibiting recurrence and metastasis and enhancing immune memory. Thus, MFMP is a potential adjunctive therapy requiring clinical validation.

Preventive effects of nitric oxide donors in contrast-induced nephropathy in patients undergoing coronary artery angiography: an updated systematic review and meta-analysis of 13 randomized controlled trials.

Contrast-induced nephropathy (CIN) is associated with increased mortality and morbidity in patients undergoing coronary angiography (CAG) and percutaneous coronary intervention (PCI). We aimed to assess the latest evidence on the preventive effects of nitric oxide (NO) donors in CIN patients undergoing CAG/PCI. We conducted a comprehensive systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, Embase, and Cochrane searches until May 5th, 2024. Dichotomous data were pooled using risk ratio (RR), and continuous data were pooled using mean difference (MD), both with a 95% confidence interval (CI), using (R version 4.3). Our analysis included 13 RCTs encompassing 3,550 patients. NO donors were significantly associated with a decreased incidence of CIN compared to placebo either as an oral administration (RR: 0.33 with 95% CI [0.26, 0.42], P < 0.01) or IV infusions (RR: 0.56 with 95% CI [0.40, 0.78], P < 0.01). Moreover, NO donors were significantly associated with decreased serum creatinine levels compared to placebo either as an oral administration (MD: - 0.07 with 95% CI [- 0.10, - 0.04], P < 0.01) or IV infusions (MD: - 0.07 with 95% CI [- 0.09, - 0.04], P < 0.01). In terms of safety, NO donors were significantly associated with a decreased incidence of major adverse cardiac events (MACE) compared to placebo as an oral administration (RR: 0.64 with 95% CI [0.45, 0.89], P < 0.01). However, there was no significant difference between NO donors as IV infusions and placebo in MACE (RR: 0.68 with 95% CI [0.38, 1.21], P = 0.18). Finally, NO donors were significantly associated with a decreased incidence of all-cause mortality compared to placebo as an oral administration (RR: 0.58 with 95% CI [0.36, 0.94], P = 0.03). Nevertheless, there was no statistically significant difference in all-cause mortality between IV infusions of NO donors and placebo (RR: 1.84 with 95% CI [0.40, 8.52], P = 0.44). NO donors as adjunct therapy are associated with reduced incidence of CIN and decreased serum creatinine levels, either as an oral or IV administration. They were also associated with reduced incidence of MACE, all-cause mortality, and recurrent myocardial infarction as an oral administration, which makes this simple, low-cost intervention an important therapeutic option in patients undergoing CAG/PCI.

Personalized Adjunctive Hemoperfusion Therapy for Refractory Septic Shock Caused by Vibrio Cholerae in Thalassemia Patient

This case report describes a patient with Beta-thalassemia/hemoglobin E that developed Vibrio cholerae septicemia, leading to refractory septic shock with a maximum norepinephrine equivalent dose of 1.84 µg/kg/min and multi-organ failure. As the patient remained in refractory shock despite receiving proper antibiotics and organ support for 48 hours, adjunctive therapy including, HA330 hemoperfusion, was initiated. Shock reversal and significant reduction of inflammatory cytokines were achieved after two intervention sessions. The patient was discharged home, despite an initial predicted mortality rate of 85% based on Acute Physiology and Chronic Health Evaluation II (APACHE II).

A Comparative Evaluation of the Antimicrobial Properties of 50% Grape Seed Extract, N-acetyl Cysteine and 5.25% Sodium Hypochlorite against Enterococcus faecalis (ATCC 19433) – An In vitro Study

Abstract Introduction: Endodontic infections are complex and polymicrobial, presenting significant challenges in dental treatment. Eliminating bacteria is the main objective of endodontic preparation, ensuring a tight seal to prevent reinfection. A commonly isolated bacterium, Enterococcus faecalis, is Gram positive and facultative anaerobic. It thrives in low-nutrient environments, forming resilient biofilms. Due to its tissue dissolving properties and broad-spectrum antimicrobial, sodium hypochlorite (NaOCl) is the most sought after irrigant, but its cytotoxicity is a concern. Alternatives such as grape seed extract (GSE) and N-acetyl cysteine (NAC) are being explored for their potential antimicrobial effects and biocompatibility. Materials and Methods: Forty single-rooted, non-carious premolars extracted for orthodontic reasons were selected. Teeth were cleaned, sectioned and prepared, ensuring apical patency. Specimens were autoclaved and contaminated with E. faecalis (ATCC 19433) for 30 days. Four groups (n = 10) were formed: Group I – GSE 50%, Group II – NAC 200 mg/ml, Group III – NaOCl 5.25% and Group IV – sodium chloride (0.9%). Manufacturer’s instructions were followed precisely to prep the solutions, and root canals were treated using the Reciproc R25 instrument. Samples were collected before (F1) and after (F2) instrumentation and irrigation. Colony-forming units (CFUs) were quantified and analysis was done using two-way analysis of variance and Tukey’s honestly significant difference post hoc tests, with significance set at P &lt; 0.05. Results: NaOCl significantly reduced CFU counts, demonstrating superior antimicrobial efficacy compared to NAC and GSE (P &lt; 0.01). In comparison to negative control and GSE (P &lt; 0.01), NAC showed significant antimicrobial activity, but not significantly different from GSE (P &gt; 0.05). GSE displayed potential antimicrobial properties but was less effective than NaOCl and NAC. Conclusion: NaOCl remains the most effective irrigant; however, NAC and GSE also demonstrated significant antimicrobial properties and could serve as adjuncts in endodontic therapy. Further research is needed to optimise their formulations and validate clinical applications.

Efficacy and safety of tanshinone IIA in combination with mesalazine in the treatment of ulcerative colitis: a Systematic review and meta-analysis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by relapsing inflammation of the colon. Tanshinone IIA, a compound derived from traditional Chinese medicine, has demonstrated anti-inflammatory properties and may enhance treatment outcomes when combined with mesalazine. This study aims to determine the overall response rate of Tanshinone IIA in combination with mesalazine for the treatment of UC. We reviewed articles from the establishment of the databases until April 2023 in the PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP, and CBM databases. They included a randomized controlled trial in which the intervention group was given tanshinone IIA plus mesalazine (T + M), while the comparative group was given only mesalazine (M). We removed duplicates or similar papers; papers with no available full text or incomplete data; animal research; and review and systematic review articles. STATA 15.1 was used to analyze the data. The perceived total effectiveness rate of T + M was found to be higher than M and the difference was found to be significant (P = 0.000). Additionally, pooled results show that TNF-α (P = 0.000) and CRP (P = 0.000) levels in the T + M group were all significantly lower than that in the M group. Furthermore, MHC-II expression in the T + M group was minors compared to that of the M group (P = 0.001). However, there was no significant difference in the incidence of adverse events between the T + M and M groups (P = 0.700). This meta-analysis demonstrates that combining tanshinone IIA with mesalazine significantly enhances the overall treatment efficacy for ulcerative colitis compared to mesalazine alone. Tanshinone IIA also exhibits anti-inflammatory effects by reducing TNF-α, CRP levels, and MHC-II expression without notably increasing adverse events. Despite some limitations, these findings suggest that tanshinone IIA can be a promising adjunctive therapy for ulcerative colitis. Further large-scale, multi-center studies are needed to confirm these results and establish the long-term safety and effectiveness of this combination therapy.

The Efficacy of Ozonated Water in One-stage Full-mouth Disinfection amongst Chronic Periodontitis Patients: A Randomised Control Trial

Abstract Introduction: Periodontal disease, causing tooth-supporting structure damage due to bacterial build-up, is linked to various risk factors. Traditional treatment involved scheduled scaling and root planing. Full-mouth disinfection (FMD), introduced in 1995, involves comprehensive cleaning and chlorhexidine (CHX) application within 24 h to prevent bacterial spread. CHX, a potent antimicrobial, is widely used in FMD, but concerns about emerging resistance have led to the exploration of alternatives like ozonated water, which has shown promising antimicrobial properties and the potential to improve periodontal health. Materials and Methods: This is a randomised controlled trial involving 40 participants with Stage II or III periodontitis who were randomly grouped into two groups. Group A was advised to use 0.2% CHX solution, and Group B used a 10 μg concentration of ozonated water. Both the groups cleaned their dorsum of the tongue, rinsed their mouth, had a pharyngeal spray and had periodontal pockets irrigated using the respective solutions. Plaque index, papillary bleeding index, gingival index, relative attachment level and probing depth were measured at baseline, 3 months and 6 months. Results: Significant differences were found at baseline, 3-month and 6-month values of periodontal index, papillary bleeding index, probing depth, gingival index and relative attachment level amongst Group A and B participants. Differences were noted in between Groups A and B in the periodontal index at 6 months between CHX and ozonated water and between 3 and 6 months for probing depth. Around 68%, 70%, 66%, 68% and 63% improvements were noted in the periodontal index, probing depth, gingival index, papillary bleeding index and relative attachment loss amongst Group B. Conclusion: Ozonated water represents a promising adjunctive therapy for chronic periodontitis, demonstrating significant clinical efficacy in one-stage FMD protocols.

Cognitive Function in Individuals with Chronic Hypoparathyroidism - A Prospective Observational Study.

"Brain fog" is a frequently reported, distressing experience among individuals with chronic hypoparathyroidism, characterized by reduced concentration and reduced ability to perform day-to-day tasks. However, evidence linking chronic hypoparathyroidism to cognitive impairment is limited and inconsistent. This study aimed to explore cognitive function in these patients using a validated neurocognitive test battery, compare results with a matched healthy control group, and analyze the frequency of cognitive impairment based on normative data. The participants' cognitive performance was tested using a cognitive test battery, including the Trail Making Test A/B, the Color-Word Interference Test, and the California Verbal Learning Test. These tests were used to evaluate the cognitive domains of "attention and processing speed," "verbal learning and memory, " and "executive function." In total, 30 individuals with hypoparathyroidism and 30 healthy controls were included. 24 patients were women (80.0%), with a median age of 44.5±13.1 and a median disease duration of 8.7 years (±5.3). Individuals with chronic hypoparathyroidism showed poorer cognitive performance in "attention and processing speed" (F(1,57) = 8.65, p = 0.005*, η² = 0.13) compared to healthy controls. A significantly higher percentage of patients had cognitive deficits in both "attention and processing speed" (56.7% vs. 3.3%) and "executive function" (60.0% vs. 16.7%). This study provides evidence that cognitive dysfunction, particularly in "attention and processing speed" is common in chronic hypoparathyroidism. Recognizing cognitive impairment in these patients is crucial, especially when discussing workability. Neuropsychological training as an adjunct therapy strategy may be beneficial in managing these cognitive deficits.

Intravenous Immunoglobulin Therapy for Pyoderma Gangrenosum: A Multicenter Retrospective Analysis in 81 Patients.

Pyoderma gangrenosum (PG) is rare neutrophil skin disease causing painful, progressively enlarging ulcers. Among the treatment options, intravenous immunoglobulin (IVIG) is a therapy of first choice for paraneoplastic PG. Otherwise, it is used in therapy-refractory courses. To assess the efficacy and safety of IVIG therapy in patients with PG. A retrospective chart review for patients in five dermatologic wound centres in Germany was performed. Overall, 81 patients were included. IVIG was used as adjunct therapy with (methyl-) prednisolone and/or a steroid sparing therapy in 77 (95.1%) cases. Response to treatment (combined complete and partial, defined as tendency to heal and cessation of lesion progression, respectively) was 49.3% 1 month after initiation of IVIG. In total 18.8% had a complete response after 6 months. Statistically significantly higher response rates were observed in patients with diabetes mellitus and thyroid disease [odds ratio (OR) 3.49, confidence interval (CI) 1.13-10.80 and OR 6.64, CI 1.01-43.57, respectively]. Patients with solid malignancy tended to have better response (OR 4.36, CI 0.79-23.91). A higher IVIG dose was also associated with a tendency towards better response rates (OR 2.70, CI 0.84-8.63). In total, 1 (1.2%) severe adverse event (myocardial infarction with consequent death) was observed as well as three moderate adverse events, with two thromboembolic events (2.5%) and one acute kidney injury (1.2%). Other adverse events were mild or unlikely to be associated with IVIG therapy, with 14 events in 10 patients overall (12.3%). This multicentre retrospective study shows the important role of adjunctive IVIG therapy in patients with PG with recalcitrant courses. Identifying subgroups with a higher probability of response could improvefuture response rates and save patients from ineffective treatment and potential adverse events.

The Inhibitory Effect of Hedera helix and Coptidis Rhizome Mixture in the Pathogenesis of Laryngopharyngeal Reflux: Cleavage of E-Cadherin in Acid-Exposed Primary Human Pharyngeal Epithelial Cells

Laryngopharyngeal reflux disease (LPRD) is a prevalent upper airway disorder characterized by inflammation and epithelial damage due to the backflow of gastric contents. Current treatments, primarily proton pump inhibitors (PPIs), often show variable efficacy, necessitating the exploration of alternative or adjunctive therapies. This study investigates the therapeutic potential of a mixture of Hedera helix and Coptidis rhizome (HHCR) in mitigating the pathophysiological mechanisms of LPRD. Using an in vitro model of human pharyngeal epithelial cells exposed to acidic conditions, we observed that acid exposure significantly increased the expression of adenosine A3 receptor (adenosine A3) and matrix metalloproteinase-7 (MMP-7), leading to E-cadherin cleavage and compromised epithelial integrity. Treatment with the HHCR mixture effectively suppressed adenosine A3 expression and MMP-7 activity, thereby reducing E-cadherin cleavage and preserving cellular cohesion. These results highlight the HHCR mixture’s ability to modulate the adenosine A3–MMP-7–E-cadherin pathway, suggesting its potential as a valuable adjunctive therapy for LPRD, particularly for patients unresponsive to conventional PPI treatment. This study provides new insights into the molecular interactions involved in LPRD and supports further clinical evaluation of HHCR as a complementary treatment option.

Clinical Impact and Safety Profile of Intravenous Lacosamide Administration as Adjunctive Therapy for Neonatal Seizures.

The aim of this retrospective descriptive study was to evaluate the clinical impact and safety profile of lacosamide in neonates with symptomatic refractory seizures.Patients diagnosed with symptomatic refractory seizures who received lacosamide were included in the study. Follow-up assessments were conducted until 24 months of age, during which data on lacosamide dosage, duration of exposure, concurrent treatments, and potential side effects were collected. A total of eight patients were enrolled, with lacosamide administered as a third- or fourth-line treatment for symptomatic refractory seizures. Following loading dose, 62.5% of the patients achieved complete remission of seizure activity without recurrence. In the remaining cases, a reduction in seizure frequency was observed. No adverse effects attributable to lacosamide were reported.In conclusion, lacosamide may be effective in achieving seizure remission in newborns with symptomatic refractory seizures, and all patients demonstrate excellent tolerance. Brief exposure to lacosamide was sufficient, and no adverse effects were observed up to 24 months of age. However, randomized controlled trials are necessary to confirm these findings.

Does adjunctive phototherapy have better outcomes than adjunctive antibiotic therapy for the management of peri-implantitis?

Elsevier's Scopus, Web of Science and Pubmed through Medline identified 431 articles, which were reduced to 206 when duplicates were removed. 8 articles were screened, and 1 excluded after reading the full-text, leaving 7 studies. 6 of these were randomised controlled trials, and 1 a non-randomised controlled clinical trial. Studies selected were either blinded, double-blinded, split-mouth clinical studies, comparative or controlled clinical studies, or randomised controlled trials in humans. There were no limitations on year of publication or language of studies. Most studies had a control of mechanical debridement (MD) with adjuvant antibiotics; 1 was surgical therapy. The test group was MD with adjuvant phototherapy. Exclusions were in vitro reports, animal studies, treatment with sole laser therapy, treatment with no additional antimicrobial therapy alongside MD. Pre-prints, reviews, abstracts, opinion articles, editorials, case reports and case series were also excluded. Data were extracted electronically by a single author and a senior librarian from the 3 databases. Titles and abstracts of articles were screened by the author if they contained Medical Subject Headings either in free terms or with Boolean operators. Full text studies that met the inclusion criteria were included. Data were also searched manually in 6 journals. For missing or conflicting information, the author of the article was contacted for clarification. Data extracted were country of origin of article, study design, sample size, research groups, diagnostic criteria, frequency of intervention, follow-up visits, and outcome of parameters which included clinically: plaque index (PI), probing depth (PD), bleeding on probing (BOP) and radiographically: crestal bone loss (CBL). Additional data on lasers were also collected, although not all studies had complete data on this. RevMan was used for statistical analysis. Inconsistencies were evaluated using I2 value > 50% and Cochrane's Q test, with a P value < 0.05 considered. Standard Mean Differences (SMD) were calculated and Confidence Interval was set at 95%. A random effects model was used for each meta-analysis. PI had no statistical difference, with high heterogeneity. PD had no statistical difference, with no heterogeneity. BOP had a statistically significant difference and a high level of heterogeneity, favouring adjunctive phototherapy. MBL had statistically non-significant differences between control and test groups, and no heterogeneity. The findings from the systematic review differed from the meta-analysis, suggesting that application of adjuvant phototherapy was equally as effective as adjunctive antibiotic therapy in outcomes such as PI, PD, BOP and MBL. The meta-analysis found that implants treated with adjuvant phototherapy had superior outcomes in relation to BOP only.

OGC SO31 - Treatment of cachexia in gastric cancer: A literature review exploring the use of natural anti-inflammatory products and their derivatives

Abstract Background Gastric cancer is a major cause of global cancer-related mortality, with 5-year survival rates of 7% in advanced disease. Cancer cachexia, characterised by irreversible skeletal muscle loss driven by systemic inflammation, contributes to approximately 20% of cancer-related deaths. Cachexia differs from malnutrition in that it cannot be fully reversed with nutritional support alone. Current treatments that focus on nutritional support, psychological counselling and anti-inflammatory medication are lacking in efficacy. Natural dietary supplements and their derivatives such as fatty acids, probiotics, amino acids, curcumin, ginger and resveratrol, may offer additional therapeutic benefits in managing gastric cancer cachexia. Method A comprehensive literature review was conducted to evaluate the efficacy of natural anti-inflammatory products in managing gastric cancer cachexia. The review focused on widely studied compounds including omega-3 fatty acids, probiotics, amino acids, curcumin, fucoidan, epigallocatechin-3-gallate (EGCG), resveratrol and ginger, assessing their impact on inflammation, muscle mass preservation, and overall patient outcomes. Results Natural anti-inflammatory compounds demonstrate efficacy in mitigating cancer cachexia by reducing systemic inflammation and muscle wasting. Essential fatty acids from nuts, seeds, and fish oil decrease pro-inflammatory cytokines and improve chemotherapy tolerance. Probiotics reduce gut dysbiosis and may enhance chemotherapy tolerance. Essential amino acids may promote muscle anabolism and reduce catabolism. Curcumin, fucoidan, EGCG and ginger exhibit anti-inflammatory properties, with some improving appetite and reducing nausea. While promising, these compounds need further clinical trials to validate their efficacy and safety in cancer cachexia management. Conclusion Natural anti-inflammatory products hold promise as adjunctive therapies in management of gastric cancer cachexia. While preclinical evidence is encouraging, robust clinical trials are essential to confirm their efficacy and safety. Integrating these compounds with conventional treatments may offer a comprehensive approach to addressing the complex metabolic and inflammatory challenges of cancer cachexia, potentially improving patient outcomes. Future research should focus on understanding mechanisms, optimising dosages, and overcoming bioavailability challenges.

Overcoming immunosuppression in cancer: how ketogenic diets boost immune checkpoint blockade.

Immune checkpoint blockade (ICB) is now part of the standard of care in the treatment of many forms of cancer, yet it lacks efficacy in some patients, necessitating adjunct therapies to support the anti-tumor immune response. Ketogenic diets (KDs), i.e., high-fat low-carbohydrate diets, have been shown to have antiproliferative and immunomodulatory effects in various preclinical cancer studies. Here, we review current knowledge of the complex interplay of KDs and the anti-tumor immune response in the context of ICB therapy, to update our understanding of diet-induced immunometabolic reprogramming in cancer. Preclinical cancer studies have revealed increased activation of and infiltration by tumor-fighting immune cells, especially CD8+ T cells, but also M1 macrophages and natural killer cells, in response to a KD regimen. In contrast, immune-suppressive cells such as regulatory CD4+ T lymphocytes, M2 macrophages, and myeloid-derived suppressor cells were reported to be decreased or largely unaffected in tumors of KD-fed mice. KDs also showed synergism with ICB therapy in several preclinical tumor studies. The observed effects are ascribed to the ability of KDs to improve immune cell infiltration and induce downregulation of immune-inhibitory processes, thus creating a more immunogenic tumor microenvironment. The studies reviewed herein show that altering the metabolic composition of the tumor microenvironment by a KD can boost the anti-tumor immune response and diminish even immunotherapy-resistant as well as immunologically "cold" tumors. However, the exact underlying mechanisms remain to be elucidated, requiring further studies before KDs can be successfully implemented as an adjunct tumor therapy to improve survival rates for cancer patients.

Abstract 4136234: Increased Reactive Oxygen Species using [18F]ROStrace PET and Dihydroethidium Staining in Myocardial Infarction Reperfusion injury

Introduction: Patients with reperfusion injury following myocardial infarction (MI) are at a higher risk of heart failure. Reactive oxygen species (ROS) activity can further damage cardiomyocytes and compromise heart function. Imaging methods are needed to assess ROS in vivo to investigate targeted adjunctive therapies. Our group developed a novel ROS-activated PET radiotracer [18F]ROStrace to fill this gap. In this study, we measured [18F]ROStrace fractional uptake rate (FUR) and for the first time compared it with histologic assessment of infarct and myocardium specimens. We hypothesized that [18F]ROStrace FUR was increased in the infarct and that [18F]ROStrace FUR was supported by [18F]ROStrace analogue dihydroethidium (DHE) staining. Methods: MI was induced in five swine, followed by reperfusion after 90 minutes. In vivo LGE CMR imaging and [18F]ROStrace and [82]Rb PET were performed at ~3-4 days after infarction. A terminal procedure was then performed. DHE and 4′,6-diamidino-2-phenylindole (DAPI) staining was done. Two swine received injections of DHE in the right and left coronary arteries to assess ROS. ROS activity was determined from [18F]ROStrace by computing the [82]Rb myocardial blood flow (MBF) corrected FUR. The linear relationship between infarct and MVO size, and MBF-corrected [18F]ROStrace FUR were calculated using the Pearson’s r. Results: There was a strong and positive correlation between infarct and MVO size (r=0.9, p=0.04). The MBF-corrected ROStrace FUR at baseline was 0.07±0.06 ml/g, infarct was 0.15 ± 0.05 ml/g, and remote was 0.09 ± 0.05 ml/g. We observed a significant difference between ROS in the infarct and remote region (p=0.01), which is also seen in the increased DHE staining in the infarct. We also observed increased DAPI staining in the infarct region compared to free wall due to the presence of inflammatory cells, thus increasing the number of nuclei. Conclusion: [18F]ROStrace is increased in the infarct during the subacute period post-MI compared to healthy and remote myocardium and supported by histological assessment. This work may lead to the use of in vivo [18F]ROStrace PET to support development of therapeutic strategies targeting ROS to reduce MI.

Abstract 4137065: Efficacy and Safety of Extracorporeal CPR in Out-of-Hospital Cardiac Arrest Survival and Neurological Integrity: a Meta-Analysis of Randomized Controlled Trials

Introduction: Out-of-hospital cardiac arrest (OHCA) remains a significant public health challenge, with conventional cardiopulmonary resuscitation (CPR) often yielding limited success. Extracorporeal CPR (eCPR) has emerged as a potential adjunctive therapy to improve outcomes in OHCA patients. Purpose: To evaluate the efficacy and safety of eCPR compared to conventional CPR in OHCA. Methods: A comprehensive search of Cochrane CENTRAL, PubMed, Ovid Medline, and Web of Science databases was conducted independently until November 10, 2023. Randomized controlled trials (RCTs) comparing eCPR with conventional CPR in OHCA were included. Primary efficacy outcome was defined as survival to hospital discharge, while primary safety outcome was assessed for bleeding events. Summary effect measures of the primary outcomes were obtained by pooling the data with an inverse variance–weighted random-effects model. A sensitivity analysis was performed regarding whether the conclusions reached might differ substantially if a single study was omitted. Statistical analyses were performed with “meta” package in R (version 4.3.2) and Revman 5.4. Results: Four unique RCTs involving 435 patients were included in the analysis. ECCPR was associated with a significantly higher rate of survival at 1 month with good neurological outcome (Risk Ratio [RR] 1.55, 95% Confidence Interval (CI) 1.06 to 2.27, I 2 : 0%) but comparable at survival to hospital discharge (RR 1.10, 95% CI 0.16 to 7.30, I 2 : 47%) compared to conventional CPR. Furthermore, no significant differences were observed between eCPR and conventional CPR groups in survival rates at 3 months (RR 1,33, 95% CI 0.92 to 1.94, I 2 : 64%), survival at 6 months with good neurological outcome (RR 1.39, 95% CI 0.97 to 1.99, I 2 : 0%), and survival at 6 months (RR 2.79, 95% CI 0.33 to 23.28, I 2 : 63%). eCPR demonstrated a statistically significant elevation in bleeding events compared to conventional CPR (RR 4.25, 95% CI 2.37 to 7.64, I 2 : 0%). Sensitivity analysis revealed that none of the studies significantly influenced the pooled risk estimate to any great extent. Conclusion: eCPR shows beneficial results in improving short-term survival and neurological outcomes at 1-month post-OHCA. However, it is associated with an elevated risk of bleeding when compared to conventional CPR. Further investigations are imperative to delineate the specific patient populations that stand to gain the most benefit from ECPR intervention.

Efficacy of Intravenous Ferric Carboxymaltose in Heart Failure Patients with Iron Deficiency Anemia: A Meta-analysis of 6271 Patients.

Iron deficiency is prevalent among heart failure patients and is associated with worse clinical outcomes, including decreased quality of life and functional capacity. This condition often results in a higher incidence of hospitalization and mortality. Iron supplementation, particularly with intravenous ferric carboxymaltose (FCM), has shown potential benefits as an adjunct therapy in heart failure management. This study aims to evaluate the efficacy of FCM in the treatment of patients with heart failure and iron deficiency anemia, with a focus on its impact on mortality and hospitalization rates. A comprehensive search was conducted in PubMed, Web of Science, and Scopus databases from their inception until 1st December 2023. Meta-analysis was performed using RevMan 5.4, employing a random-model effect. The results were reported as risk ratios (RRs), standard mean differences (SMDs), and 95 % confidence intervals (CIs). The meta-analysis included 13 studies with a total of 6271 patients. Ferric carboxymaltose administration resulted in a significant improvement in the 6-minute walk distance (SMD: 1.45; 95 % CI: 0.55, 2.36; p = 0.002), quality of life, as assessed by the Kansas City Cardiomyopathy Questionnaire (KCCQ) (SMD: 1.49; 95 % CI: 0.87, 2.11; p < 0.00001), the rate of first hospitalization for heart failure or cardiovascular death (RR: 0.91; 95 % CI: 0.84, 0.98; p = 0.02). However, FCM did not show a significant impact on the risk of cardiovascular death (RR: 0.90; 95 % CI: 0.77, 1.05; p = 0.17), the need for intervention due to worsening heart failure (RR: 0.41; 95 % CI: 0.04, 4.51; p = 0.47), or all-cause mortality rates (RR: 0.89; 95 % CI: 0.69, 1.16; p = 0.28). While FCM treatment in patients with heart failure and iron deficiency anemia significantly improves functional capacity and quality of life, it has no notable effect on mortality rates or the likelihood of hospitalization. These findings highlight the need for further research to explore comprehensive treatment strategies that address both the symptomatic and survival aspects of heart failure management in this patient population.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) as treatment for nicotine cessation in psychiatric populations: a systematic review.

Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation. Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science,Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria. Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)]. The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and preventionof NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD.

SURG-48. LASER INTERSTITIAL THERMAL THERAPY REMODELS THE TUMOR IMMUNE LANDSCAPE IN A MOUSE GLIOMA MODEL

Abstract BACKGROUND Laser interstitial thermal therapy (LITT), a minimally invasive surgical technique for tumor ablation, is increasingly being used to treat primary and recurrent glioma. While the primary goal of using LITT has been to destroy tumor tissue, little is known about the impact of LITT on the overall immune response. To investigate changes in the tumor immune landscape, we utilized a mouse model of LITT and applied it to a poorly immunogenic mouse model of glioma. METHODS SB28 glioma cells were implanted in the right frontal lobe of C57BL/6 mice, and on day 7, an optical fiber is inserted into the tumor, paired with a thermocouple for real-time temperature monitoring. A 30W laser was activated in pulses to maintain a peri-lesional temperature of 44C for 150-180 seconds. The tumor and LITT-associated immune response was analyzed by multiparameter flow cytometry, single cell RNA-seq, and multiplex immunofluorescence. RESULTS LITT (versus sham control) triggered an increase in neutrophils in the tumor during the acute phase at day 3 following treatment. Total immune cell numbers increased over time in both sham- and LITT-treated mice, but there was a significant increase at post-LITT day 7 in select adaptive immune cell populations including type 1 conventional dendritic cells, NK cells, and gamma delta T cells. Monocytes/macrophages comprised the majority of the immune infiltrate, and multiplex immunofluorescence revealed these populations localized to the perimeter of the LITT lesion. scRNA-seq also revealed enrichment of a Fabp5- and Gpnmb-expressing macrophage subset following LITT. CONCLUSIONS LITT modifies the tumor immune infiltrate with increases in neutrophils as well as select adaptive cell and macrophage subsets. Future studies will explore adjunct therapies to further augment the immune response in the setting of LITT.

Effects of Nigella sativa on disease activity, T lymphocytes and inflammatory cytokine profiles in pediatric systemic lupus erythematosus: A randomized controlled trial

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, requiring long-term treatment that can have side effects, particularly in pediatric patients. Nigella sativa (NS) has shown potential for improving SLE symptoms due to its anti-inflammatory and immunomodulatory effects. The aim of this study was to investigate the immunomodulatory effect of N. sativa oil (NSO) on disease activity, T lymphocyte activity and inflammatory cytokine profiles in pediatric SLE patients. A randomized, double-blinded, placebo-controlled clinical trial was conducted at Saiful Anwar Hospital in Malang, Indonesia, from January 2022 to January 2023. Pediatric patients with SLE were randomly assigned to receive either one gram of NSO or a placebo containing starch in capsule form as adjunct therapy alongside their SLE primary treatment. Blood samples were collected before treatment and after eight weeks of daily capsules. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K); flow cytometry was used to identify T helper lymphocytes, and serum cytokine levels were measured using ELISA. The statistical analysis tests were performed to compare the outcomes between groups at baseline or after the treatment, and within-group comparisons before and after the study period, as appropriate. A total of 32 patients were included in the study. A significant decrease in the SLEDAI-2K score was observed at post-treatment in both the NSO and placebo groups (p&lt;0.001 and p=0.025, respectively). The percentage of T helper 17 (Th17) cells was significantly reduced in both the NSO and placebo groups post-treatment compared to pre-treatment (p=0.026 and p=0.034, respectively). Conversely, the post-treatment percentage of regulatory T (Treg) cells increased significantly in both groups. A significant reduction in interleukin (IL)-2 levels was observed in the NSO and placebo groups at post-treatment compared to pre-treatment (p=0.006 and p=0.046, respectively). Additionally, there were increases in IL-4 and IL-6 serum levels in both groups at post-treatment compared to pre-treatment (p&lt;0.05). This study highlights that although disease activity was not significantly different between NSO and placebo groups, NSO could affect the inflammatory cytokine profiles in pediatric SLE patients.

Renoprotective Effects of Brown-Strain Flammulina velutipes Singer in Chronic Kidney Disease-Induced Mice Through Modulation of Oxidative Stress and Inflammation and Regulation of Renal Transporters

Cisplatin, widely used in chemotherapy, acts through mechanisms such as oxidative stress to damage the DNA and cause the apoptosis of cancer cells. Although effective, cisplatin treatment is associated with considerable side effects including chronic kidney disease (CKD). Studies on brown-strain Flammulina velutipes Singer (FVB) have shown its significant antioxidant and immunomodulatory effects. High-performance liquid chromatography (HPLC) confirmed that the FVB extract contained gallic acid and quercetin. This study investigated whether FVB extract can improve and protect against cisplatin-induced CKD in mice. C57BL/6 mice were used as an animal model, and CKD was induced through intraperitoneal cisplatin injection. FVB was orally administered to the mice for 14 consecutive days. N-acetylcysteine (NAC) was administered in the positive control group. Organ pathology and serum biochemical analyses were conducted after the mice were sacrificed. Significant dose-dependent differences were discovered in body mass, kidney mass, histopathology, renal function, inflammatory factors, and antioxidant functions among the different groups. FVB extract reduced the severity of cisplatin-induced CKD in pathways related to inflammation, autophagy, apoptosis, fibrosis, oxidative stress, and organic ion transport proteins; FVB extract, thus, displays protective physiological activity in kidney cells. Additionally, orally administered high doses of the FVB extract resulted in significantly superior renal function, inflammatory factors, antioxidative activity, and fibrotic pathways. This study establishes a strategy for future clinical adjunctive therapy using edible-mushroom-derived FVB extract to protect kidney function.