Treatment Options Research Articles

A vagus nerve dominant tetra-synaptic ascending pathway for gastric pain processing.

Gastric pain has limited treatment options and the mechanisms within the central circuitry remain largely unclear. This study investigates the central circuitry in gastric pain induced by noxious gastric distension (GD) in mice. Here, we identified that the nucleus tractus solitarius (NTS) serves as the first-level center of gastric pain, primarily via the vagus nerve. The prelimbic cortex (PL) is engaged in the perception of gastric pain. The lateral parabrachial nucleus (LPB) and the paraventricular thalamic nucleus (PVT) are crucial regions for synaptic transmission from the NTS to the PL. The glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry is necessary and sufficient for the processing of gastric pain. Overall, our finding reveals a glutamatergic tetra-synaptic NTS-LPB-PVT-PL circuitry that transmits gastric nociceptive signaling by the vagus nerve in mice. It provides an insight into the gastric pain ascending pathway and offers potential therapeutic targets for relieving visceral pain.

Current status of evaluation and treatment of early-stage remnant gastric cancer

Because of early diagnosis and improved prognosis, patients with gastric cancer are now surviving longer and remnant gastric cancer after gastrectomy is becoming more common. Remnant gastric cancer is traditionally considered a malignancy with a dismal outcome. However, recent advances in diagnostic and therapeutic strategies have improved outcomes. In recent years, the development of endoscopic therapy has provided us with new therapeutic ideas. Although with some drawbacks, such as limited working space, gastric fibrosis and staples under the suture line, endoscopic management is still an effective treatment option with potential long-term survival advantage. For gastrectomy patients, endoscopic surveillance should also be recommended, for prompt surveillance and detection in the early remnant gastric cancer. This review aims to provide an overview of remnant gastric cancer, especially focusing on its pathogenesis as well as new advances in the diagnosis and endoscopic treatment of early-stage remnant gastric cancer.

Abstract PR005: Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level

Abstract Liquid biopsies present a promising, minimally invasive procedure through which clinicians can assess and monitor disease status by interrogating circulating tumor cell (CTC) and immune cell phenotypes. In the case of Small-cell lung cancer (SCLC) – a type of lung cancer characterized by aggressive growth, dismal prognosis and limited treatment options - leveraging liquid biopsies and CTCs for evaluating disease status would be of great benefit, given that biopsies are scarce. Furthermore, SCLC CTC numbers are higher compared to other cancers, presenting a unique opportunity to utilize them for assessing SCLC therapy resistance and identifying new targetable markers. In this study, we leverage mass cytometry (i.e. CyTOF) to phenotype SCLC CTC phenotypes in longitudinal clinical specimens to assess therapy resistance at a personalized level. By using CyTOF - a multiplex cytometric approach that enables interrogation of 30-50 protein markers per single cell – we show that we are able to identify and analyze a significant number of CTCs and their heterogeneous expression profiles. To achieve this, we first optimized a CyTOF panel of ∼25-30 antibodies by using SCLC cell lines and blood specimens from healthy donors and SCLC patients. We show that by using this approach, we are able to identify and phenotype SCLC CTCs by using the combination of CD45 (negative expression) and CD56 positive expression with further validation achieved by TTF1 and SCLC subtype transcription factor expression (NEUROD1, POU2F3 and ASCL1). This approach avoids enriching for specific CTC epithelial phenotypes that express surface markers that fluctuate during epithelial- mesenchymal transition (EMT) (e.g. EpCAM, a common marker for isolating CTCs). For parallel immune profiling we assessed among others CD8/CD4 (T cells) and CD11b/HLA-DR (Myeloid-derived suppressor cells, MDSCs) expression. We then proceeded to interrogate CTC phenotypic differences in the naïve vs relapsed setting as well as dynamic changes in longitudinal blood specimens from SCLC patients by evaluating markers that describe immune suppression activity (PD-L1) and EMT status (E-Cadherin, Vimentin, MUC1, Twist and Slug). Importantly, we show that with our approach we can track in real time therapeutic targets that are currently being tested in clinical trials or have been recently FDA approved (e.g. pYAP and DLL3) and found that MUC1 and pYAP are significantly increased in CTCs detected in blood specimens of SCLC relapsed patients. Our immune profiling showed an increase of MDSC percentages and a decrease in the CD4/CD8 T cell ratio in the relapsed setting. Finally, when we used PHENOSTAMP, a previously developed reference EMT map for assessing EMT phenotypes in lung cancer clinical specimens, we observed an increase of EMT heterogeneity in CTCs in relapsed patients. Our study highlights the translational power of our approach in utilizing CyTOF for longitudinally tracking CTCs directly in SCLC patient liquid biopsies towards assessing therapy response and resistance at a personalized level. Citation Format: Loukia G Karacosta, Sayantan Bhattacharyya, Allison Stewart, Ashley Victorian, Ester F Lujan, Shafqat Ehsan, Subin Kim, Alberto Duarte, Runsheng Wang, Benedict Anchang, Jing Wang, Lauren Byers. Leveraging mass cytometry for phenotyping CTCs in SCLC liquid biopsies: Tracking therapy resistance at a personalized level [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr PR005.

Abstract Su701: The Influence of Public Assistance Among Patients Who Received Extracorporeal Cardiopulmonary Resuscitation after Cardiac Arrest in Japan

Background: This study aimed to evaluate the influence of public assistance on patients with out-of-hospital cardiac arrest (OHCA) who received extracorporeal cardiopulmonary resuscitation (ECPR) in Japan. Methods: We conducted a secondary analysis of data from the SAVE-J II study, a retrospective, multicenter registry study involving 36 participating institutions in Japan. Patients with cardiac arrest who received ECPR were divided into two groups depending on whether or not they had received public assistance. The primary outcome was 30-day survival. Secondary outcomes were as follows: 30-day favorable neurological outcomes (cerebral performance category scores 1-2); survival at discharge; favorable neurological outcome at discharge; number of intensive care unit, hospital, ventilator, and extracorporeal membrane oxygenation days; medical expenses; proportion of percutaneous coronary intervention; target temperature management; mechanical circulatory support (MCS) device use; and withdrawal of life-sustaining therapy. Results: Of 2,157 patients registered in the SAVE-J II study, 1,885 patients were enrolled in this study; 99 patients (5.3%) received public assistance and 1,786 patients (94.7%) did not. Multivariable logistic regression analysis did not show a significant difference in 30-day survival (OR 1.22, 95% CI 0.77-1.95, p=0.40). The log-rank test for the Kaplan-Meiercurve on 30-day survival did not demonstrate a significant difference (p=0.46). Except for the use of MCS devices, there were no significant differences in secondary outcomes. Conclusions: The use of public assistance did not influence the prognoses of OHCA patients receiving ECPR. Treatment option during hospitalization may be affected by the use of public assistance.

Chronic airway diseases: a new frontier in interventional pulmonology

As medical science has advanced, the incidence of central airway lesions, traditionally the primary focus of interventional pulmonology, has decreased significantly. However, the large population suffering from chronic airway diseases, coupled with unmet treatment needs and a high demand for new technologies and methods, has greatly driven the innovation and application of interventional respiratory techniques. The development and clinical application of techniques such as lung volume reduction, targeted lung denervation, pulsed electric field technology, bronchial thermoplasty, and regenerative medicine for chronic airway diseases are providing new treatment options. Chronic airway diseases are becoming a new frontier in interventional pulmonology.

The Discourse Surrounding Polycystic Ovary Syndrome on TikTok: A Social Media Analysis

Background/Objectives: Individuals are turning increasingly towards online resources, such as TikTok, to educate themselves on their medical conditions. Polycystic ovary syndrome (PCOS) is a prominent example, as women report dissatisfaction with the diagnosis process and treatment options. This study aims to provide a content analysis of the quality of PCOS health information on TikTok. Methods: A total of 325 TikTok videos were screened. Pertinent data, including likes, comments, shares, and views, along with video content concerning symptoms, interventions, and provider interactions were analyzed. Two reviewers independently used a modified DISCERN criteria to assess the quality of information for each video. A logistic regression was also utilized to model the probability of healthcare professionals creating educational videos. Results: A total of 238 videos met the eligibility criteria for analysis. Videos had a median of 468,400 views (Q1 = 146,400, Q3 = 1,100,000) and 18,000 likes (Q1 = 5631, Q3 = 65,100). The mean modified DISCERN scores were 3.6 ± 0.9 for physicians (n = 23), 2.0 ± 1.1 for non-physician healthcare providers (n = 52), and 1.0 ± 0.2 for non-healthcare professionals (n = 141) (p < 0.001). Healthcare professionals were 10.9 times more likely to create educational videos in comparison to non-healthcare professionals (p < 0.001). Conclusions: TikTok videos related to PCOS attract considerable engagement but provide low-quality information. Most videos were made by non-healthcare professionals, who discussed treatment options with limited or no research. Healthcare providers should be aware of the impacts on patients’ preconceived notions and help to improve patient education.

Psychological well-being of women with uterine infertility before considering uterus transplantation as a treatment option.

While uterus transplantation offers a promising treatment option for women with uterine factor infertility (UFI), the potential for graft failure and lack of organ availability could have subsequent psychological repercussions for women. Exploring baseline psychological well-being for women with UFI who could become uterine transplant recipients is essential to identify specific psychological challenges to be considered prior to transplantation. UFI can be congenital uterine absence, namely Mayer-Rokitansky-Küster-Hauser syndrome (MRKH), or acquired uterine absence (hysterectomy). To analyse baseline psychological well-being among women with UFI. A survey including demographic data and two internationally validated psychological questionnaires, Depression, Anxiety and Stress Scale (DASS-21),13 and Fertility Quality of Life (FertiQoL), was disseminated to women with UFI. Data from these instruments was compared between groups and then to data that uses these tools in the general infertility population. The study included 39 women (mean age 29.54 years). Higher scores for moderate symptoms of depression, anxiety, and stress were reported for the entire UFI cohort. More women with congenital UFI showed 'severe' symptoms for depression/anxiety, compared to women with acquired UFI. Women with acquired UFI showed poorer FertiQoL scores compared to both women with congenital UFI and to the general infertility population scores in previously published data. Clinicians should consider accessing increased psychological support for women with UFI when discussing fertility options including uterine transplant, and they may need to tailor this support depending on whether the patient has congenital or acquired UFI.

Phyto-pharmaceuticals as a safe and potential alternative in management of psoriasis: a review.

Psoriasis is a chronic autoimmune skin disease with a worldwide prevalence of 1-3 % results from uncontrolled proliferation of keratinocytes and affects millions of people. While there are various treatment options available, some of them may come with potential side effects and limitations. Recent research has shown that using bioactive compounds that originate from natural sources with a lower risk of side effects are relatively useful in safe management psoriasis. Bioactive compounds are molecules that are naturally available with potential therapeutic efficacy. Someof bioactive compounds that have shown promising results in the management of psoriasis include curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, etc., possess anti-inflammatory, antioxidant, immunomodulatory, and anti-proliferative properties, with capabilities to suppress overall pathogenesis of psoriasis. Moreover, these bioactive compounds are generally considered as safe andare well-tolerated, making them potential options for long-term use in the management of various conditions linked with psoriasis. In addition, these natural products may also offer a more holistic approach to treat the disease, which is appealing to many patients. This review explores the bioactive compounds in mitigation of psoriasis either innative or incorporated within novel drug delivery. Moreover, recent clinical findings in relation to natural product usage have been also explored.

Loncastuximab tesirine in previously treated diffuse large B-cell lymphoma: A plain language summary of the LOTIS-2 study.

This article provides a plain-language summary of the results of a clinical trial called the LOTIS-2 study.The LOTIS-2 study included 145 participants with an aggressive type (one that forms, grows, or spreads quickly) of non-Hodgkin lymphoma called diffuse large B-cell lymphoma (a type of blood cancer), or DLBCL for short, whose disease came back or did not respond after 2 or more previous treatments. The LOTIS-2 study was conducted from August 2018 to September 2022.Participants received loncastuximab tesirine, also referred to as Lonca, for up to 1year, or longer if the treatment was working, and their health was monitored. The primary purpose of the LOTIS-2 study was to find out if participants' lymphoma shrank partially or completely after receiving Lonca. A total of 145 participants who were treated with Lonca lived a median (meaning the middle value in a set of numbers) of 9.5months after starting Lonca treatment. The lymphoma shrank partially or completely in nearly half of participants and shrank completely in 1 in 4 participants. Among participants whose disease either shrank partially or completely in response to Lonca treatment, responses happened relatively quickly, with a median time to response (the time between starting treatment and when the participant's lymphoma either partially or completely shrank) of 41days. In these participants, the lymphoma did not grow or come back for a median of 13.4months. Researchers estimated that 83% of participants whose disease shrank completely remained disease free for at least 1year.Nearly all participants had a side effect from Lonca treatment. The most common side effects were abnormal liver tests (increased gamma-glutamyl transferase), decreased white blood cells (neutropenia), and decreased platelets (thrombocytopenia). One in 4 participants had their treatment stopped due to side effects. The most common side effects that resulted in participants needing to stop Lonca treatment were abnormal liver tests (increased gamma-glutamyl transferase), swelling in the arms or legs (peripheral edema), swelling in an individual spot (localized edema), and fluid around the lungs (pleural effusion). These results show that Lonca is a treatment option with controllable side effects for many patients with DLBCL whose disease did not respond or came back after 2 or more previous treatments. For participants whose lymphoma completely shrank while taking Lonca, those responses to treatment occurred quickly and lasted for over a year.

Abstract 4136023: Eligibility and Barriers of Mavacamten Therapy in Patients with Hypertrophic Cardiomyopathy: A Retrospective Analysis

Background: Hypertrophic Cardiomyopathy (HCM) is a common genetic heart disorder characterized by the thickening of the myocardium. Mavacamten has emerged as a novel medication for targeted therapy in HCM patients, but its adoption faces multiple hurdles. This study aims to evaluate the eligibility of HCM patients for Mavacamten treatment based on certain clinical criteria and to promote consideration of potential barriers patients face in obtaining this medication. Methods: We conducted a retrospective analysis of 115 HCM patients at Truman Medical Center that included demographic data, clinical characteristics, and treatment histories. Patient eligibility for Mavacamten was determined based on ejection fraction (EF) > 55%, symptomatic obstructive HCM, and intolerance to first-line therapy (beta-blockers, calcium channel blockers). Statistical analysis was performed using standard deviation and mean comparisons to estimate the proportion of eligible patients. Results: Out of 115 patients, 96 patients have an EF>55%. 76 patients (66.1%) have a clinical heart failure diagnosis. 94 patients (81.7%) are taking beta-blockers. 49 patients (42.6%) have uncontrolled hypertension indicated by blood pressure >140. Considering these factors, 49 (42.6%) met the clinical criteria for Mavacamten treatment. Of these patients eligible to receive Mavacamten treatment, only one patient was actively taking Mavacamten. The most common obstacles to receiving the drug included lack of insurance coverage, high medication cost, and limited awareness among healthcare providers regarding new treatment options. Conclusion: While a considerable proportion of HCM patients qualify for Mavacamten based on clinical criteria, external factors significantly impede access to this potentially life-altering treatment. Efforts should address this treatment gap through raising awareness to healthcare professionals and improving insurance coverage. This will enhance patient access to Mavacamten, ultimately improving outcomes in HCM management. This study summarizes the eligibility and obstacles to Mavacamten in a sample of HCM patients, emphasizing the need for systemic changes to facilitate access to advanced therapies.

Efficacy and safety of DTG plus 3TC for prophylaxis of perinatal transmission of HIV infection in pregnant women who have detectable viral load after 14 weeks of gestation: A pilot study (PREGNANCY)

Abstract Background The prevention of perinatal HIV transmission depends on the safe and effective use of antiretroviral therapy (ART). Simplifying treatment reduces drug exposure for both mother and child. We evaluated the safety and efficacy of DTG/3TC for antiretroviral-naïve pregnant women living with HIV (PWLHIV). Methods This proof-of-concept trial enrolled ART-naïve pregnant women over 15 years old with HIV infection and a gestational age between 14 and 28 weeks. Participants received a fixed-dose combination of DTG/3TC. Baseline HIV genotyping was performed. Participants were monitored at baseline, every 4 weeks, and at delivery. Infants were assessed at birth, 4 weeks, and 6 weeks of age. Outcomes included the proportion of women achieving an undetectable HIV-1 plasma viral load (<50 copies/mL) at delivery, therapy modification frequency, perinatal HIV transmission rate, and adverse events. Results Between January 2019 and March 2021, 20 women were enrolled. At baseline, the median CD4 cell count was 401.6 ± 113.6 cells/μL, increasing to 690.2 ± 266 cells/μL at delivery. Median viral load was 9,514 copies/mL. All women achieved an undetectable viral load after an average of 40 days. No cases of perinatal HIV transmission were detected. No therapy modifications were necessary during the study, and no adverse events were related to the ART. Conclusion In this pilot trial, DTG/3TC demonstrated safety and efficacy, with all participants achieving viral suppression before delivery. There were no cases of perinatal HIV transmission and no drug-related adverse events. DTG/3TC can be an option for initial treatment of drug-naïve PWLHIV.

Abstract 4138545: Mitral Valve Replacement is associated with favourable Functional and Clinical Outcome as compared with Restrictive Mitral Annuloplasty in Patients with Severe Ischemic Mitral Regurgitation. A prospective longitudinal analysis

Background: Restrictive mitral annuloplasty (RMA) and chordal-sparing mitral valve replacement (MVR) are common options for treatment of chronic severe ischemic mitral regurgitation. Research question: in patients with severe ischemic mitral regurgitation the most effective surgical approach remains controversial Aim: to test whether MVR provides superior clinical and functional outcomes compared with RMA. Methods: a prospective longitudinal analysis on 187 patients (age: 66 ± 9 year; EF:35 ± 8 %) undergoing MVR or RMA and CABG for severe ischemic mitral regurgitation. Six-minute walking test and echocardiography were performed at preoperative baseline, at 1 year and at a median FU of 5 year (interquartile range: 2.9). Brain natriuretic peptide levels were also obtained. Mitral regurgitation was defined through a comprehensive and integrative approach. Recurrent mitral regurgitation was defined as a vena contracta ≥ 3 mm at follow-up, in patients with no persistent regurgitation at discharge. The primary outcome was a 5-year composite of all-cause mortality and rehospitalization for heart failure. Survival analysis was performed with Kaplan-Meier method. Cox regression analysis was used to verify any independent predictor of composite end-point Results: Baseline preoperative data were similar between the two group. Mitral valve replacement was performed in 49% of patients (n=92) and RMA in 51 % (n=95). At 5 year patients referred to prostheses showed significant improvement in six-minute walking test as compared to RMA (MVR: 290 ± 70 meters vs MRA: 165± 56 meters) (p > 0.01) ( Figure 1 ). The brain natriuretic peptide values did not differ between the two group at 1 year whereas were significantly lower in the MVR group at 5 years (MVR: 135 pg/ml; interquartile range:100 vs RMA: 486 pg/ml; interquartile range: 68 (p<0.01) ( Figure 2 ). At 5 years freedom from all-cause death and rehospitalization for heart failure was higher in the MVR group as compared to RMA (84 ±8.9% vs 61 ±12%, p<0.01) ( Figure 3 ). According to the Cox analysis recurrent mitral regurgitation was found to be a predictor of clinical outcome (HR:5.4, 95% CI:1.3-23.2, p= 0.023). Conclusions: In patients with severe ischemic mitral regurgitation referred for surgery, chordal- sparing MVR and CABG may improve functional capacity, clinical outcome and brain natriuretic peptide levels, compared with RMA and CABG. The impact of these findings remains to be defined by larger studies on longer term

Total Contact Casting Remains an Effective Modality for Treatment of Diabetic Foot Ulcers.

Total contact casting (TCC) is used to promote wound closure in diabetic foot ulcers (DFUs); however, this technique is underused today. This study aims to further evaluate the efficacy of TCC in a large cohort, including patients with peripheral artery disease (PAD). This was a retrospective analysis of patients with DFUs who underwent TCC from 2017 to 2021. PAD was defined as absence of pedal pulse or ABI <0.9. Demographic data, DFU characteristics, and peripheral arterial intervention were evaluated. Outcomes included complete healing, healing time, and rate of major amputation. Subgroup analysis was performed on patients undergoing peripheral intervention. 152 patients underwent TCC. Mean age was 58.8 ± 12.1years, 79.6% were male, and 26.3% had PAD. Mean DFU size was 8.27 ± 9.9cm2, with mean depth 0.61 ± 0.49cm. 112 patients had palpable pedal pulses on the affected extremity (73.7%). Average ABI was 1.12 ± 0.22 (n = 90). Complete healing was observed in 122 (80.3%) patients, with average healing time of 81.5 ± 57.1days. Thirteen (8.6%) patients eventually required amputation (3 major). When compared to patients with healed DFUs, those without healing had higher rates of amputation (39.1% vs 3.1%, P < .001), intervention (43.4% vs 17.8%, P = .006), and noncompliance (39.1% vs 20.2%, P = .046). Thirty-three patients underwent revascularization, undergoing angioplasty (81.8%), atherectomy (63.6%), stent (15.2%), and/or bypass (9.1%). Interventions were performed in aortoiliac (3.0%), femoropopliteal (45.5%), and tibial (72.7%) segments. Twenty-two (66.7%) patients who underwent revascularization completely healed. Patients requiring revascularization were more likely to have previous intervention (57.6% vs 13.4%, P < .0001) and incompressible vessels (36.4% vs 7.6%, P < .00001), with lower ABIs (0.94 ± 0.25 vs 1.17 ± 0.18, P = .0008) compared to patients without intervention. TCC remains an effective option for treatment of DFUs, as most were completely healed. Patients with PAD may benefit from TCC and revascularization, however, healing rates are lower in this cohort, necessitating the need for close observation.

Abstract 4125106: Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis; A Meta-Analysis.

Background: Internationally, drug-coated balloons have emerged as a new treatment approach in In-Stent Restenosis (ISR) offering localized drug delivery to inhibit neointimal growth without the need for additional stent layers. However, their use has not been assessed or approved in the United States. Paclitaxel-coated balloons (PCBs) are gaining traction as alternatives for in-stent restenosis patients. Yet, their safety and effectiveness compared to uncoated balloons remain uncertain. This meta-analysis seeks to systematically assess PCBs' safety and efficacy for ISR treatment by comparing them to uncoated balloons. Research Question: Are paclitaxel-coated balloons (PCBs) superior to uncoated balloons (UCBs) in terms of safety and efficacy for the treatment of coronary in-stent restenosis (ISR)? Aims: Systematically assess the safety and efficacy of paclitaxel-coated balloons (PCBs) compared to uncoated balloons (UCBs) for the treatment of coronary in-stent restenosis (ISR). Methods: A comprehensive literature review was conducted utilizing multiple databases up to May 2024, focusing on randomized controlled trials comparing PCB vs UCB in patients with coronary in-stent restenosis. Six randomized controlled trials with a total of 1,347 patients who completed 1-year follow-up were included. Dichotomous data were calculated as odds ratios (ORs) and 95% confidence intervals (95% CI). P&lt;0.05 was considered to indicate a statistically significant difference. The primary outcomes included Target Lesion Revascularization (TLR), Myocardial Infarction (MI), Stent Thrombosis (ST) and Total Mortality (TM). Results: Compared with patients who underwent UCB angioplasty, those in the PCB group exhibited a clear superiority in TLR [odds ratio (OR), 0.21; 95% CI [ 0.11,0.41]; P&lt;0.00001], and MI [odds ratio (OR), 0.55; 95% CI [0.33,0.91]; P&lt;0.02]. ST was numerically lower in the PCB arm without statistical significance (OR, 0.21; 95% CI [0.03,1.48]; P=0.11). TM was also numerically lower with PCB without reaching statistical significance (OR, 0.60; 95% CI [0.32,1.11]; P=0.10). Conclusion: This meta analysis supports that PCBs are associated with superior outcomes when compared with UCBs in the management of ISR. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis as demonstrated by superior outcomes in target lesion revascularization and recurrent myocardial infarction.

Abstract 4119611: Catheter ablation approach and outcome in HIV+ patients with atrial fibrillation: a systematic review and meta-analysis

Background: Catheter ablation has emerged as an effective treatment option for atrial fibrillation (AF) in the general population. However, limited data exist on the outcomes of catheter ablation in patients infected with the Human Immunodeficiency Virus (HIV+) with concomitant AF. Objectives: This systematic review and single arm meta-analysis aims to comprehensively evaluate the literature on catheter ablation approach and outcome in HIV+ patients with AF. Methods: A systematic search of PubMed, Embase, and Cochrane Central Register of Controlled Trials was conducted following PRISMA guidelines.Studies meeting the intervention of catheter ablation for AF in HIV+ patients, using radiofrequency, cryoballoon, or pulsed field ablation techniques, were included and data were collected and synthesized using proportion meta-analysis techniques. Statistical analysis was carried out using R software. Results: Three studies met the inclusion criteria, involving 89 HIV+ patients, with an average age of 51.5 years, of whom 83.1% were men, undergoing catheter ablation. Two studies performed received isolation of the pulmonary vein (PV) + posterior wall and superior vena cava. And one study evaluated only the isolation of the pulmonary veins. Of these patients, 43.8% had paroxysmal AF and 56.1% had persistent AF. In two studies reporting freedom from atrial arrhythmias, all patients (62) experienced recurrence of atrial arrhythmias within 5 years of follow-up. Freedom from repeat ablation was 6.26% (Figure 1A). The rate of Pulmonary Vein Trigger was 31.28% (Figure 1B), while the rate of Non-Pulmonary Vein Trigger (non-PV) was 76.64% (Figure 1C). Conclusion: In this systematic review and meta-analysis assessing outcomes of ablation in HIV patients with AF, we observed a similar prevalence of paroxysmal and persistent AF. Furthermore, contrary to the non-HIV+ patients, a high incidence of non-pulmonary vein triggers of AF was noted in this population.

Machine learning model reveals the role of angiogenesis and EMT genes in glioma patient prognosis and immunotherapy.

Gliomas represent a highly aggressive class of tumors located in the brain. Despite the availability of multiple treatment modalities, the prognosis for patients diagnosed with glioma remains unfavorable. Therefore, further exploration of new biomarkers is crucial to enhance the prognostic assessment of glioma and to investigate more effective treatment options. In this research, we utilized multiple machine learning techniques to assess the significance of genes related to angiogenesis and epithelial-mesenchymal transition (EMT) in the context of prognosis and treatment for glioma patients. The random forest algorithm highlighted the significance of CALU, and further analysis indicated that the effect of CALU on glioma progression may be regulated by MYC. Different machine learning approaches were employed in our investigation to uncover crucial genes associated with angiogenesis and EMT in glioma. Our findings verify the connection between these genes and the prognosis of patients with glioma, as well as the results of immunotherapeutic interventions. Notably, through experimental verification, we identified CALU as a new prognostic marker for glioma, and inhibiting the expression of CALU can impede the progression of glioma.

Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience

Introduction: Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure. Aim: To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients. Methods: Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed. Results: A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV Conclusion: Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.

Analysis of the Prevalence of Bacterial Pathogens and Antimicrobial Resistance Patterns of Edwardsiella piscicida in Largemouth Bass (Micropterus salmoides) from Guangdong, China

To gain insights into the prevalence and antimicrobial resistance patterns of major bacterial pathogens affecting largemouth bass (Micropterus salmoides) in the Pearl River Delta (PRD) region, Guangdong, China, a study was conducted from August 2021 to July 2022. During this period, bacteria were isolated and identified from the internal organs of diseased largemouth bass within the PRD region. The antimicrobial resistance patterns of 11 antibiotics approved for use in aquaculture in China were analyzed in 80 strains of Edwardsiella piscicida using the microbroth dilution method. The results showed that 151 bacterial isolates were obtained from 532 samples, with E. piscicida (17.29%, 92/532), Aeromonas veronii (4.70%, 25/532), and Nocardia seriolae (2.26%, 12/532) being the main pathogens. Notably, E. piscicida accounted for the highest proportion of all isolated bacteria, reaching 60.92% (92/151), and mainly occurred from November to April, accounting for 68.48% (63/92) of the cases. The symptoms in largemouth bass infected with E. piscicida included ascites, enteritis, and hemorrhaging of tissues and organs. The drug sensitivity results showed that the resistance rates of all E. piscicida strains to ciprofloxacin, all sulfonamides, thiamphenicol, florfenicol, enrofloxacin, doxycycline, flumequine, and neomycin were 96.25%, 60–63%, 56.25%, 43.75%, 40%, 32.5%, 16.25%, and 1.25%, respectively. In addition, 76.25% (61/80) of these strains demonstrated resistance to more than two types of antibiotics. Cluster analysis revealed 23 antibiotic types (A–W) among the 80 isolates, which were clustered into two groups. Therefore, tailored antibiotic treatment based on regional antimicrobial resistance patterns is essential for effective disease management. The findings indicate that in the event of an Edwardsiella infection in largemouth bass, neomycin, doxycycline, and flumequine are viable treatment options. Alternatively, one may choose drugs that are effective as determined by clinical drug sensitivity testing.

Melasma Management: A Comprehensive Review of Treatment Strategies Including BTX-A.

Botulinum toxin A (BTX-A) is a widely utilized protein derived from the bacterium Clostridium botulinum, known for its effectiveness in treating various medical conditions involving muscle spasticity, involuntary muscle movements, and pain disorders. Beyond its therapeutic applications, BTX-A is also commonly used in cosmetic procedures to address dynamic wrinkles, hyperhidrosis, sebum production, pore size, and overall skin texture. While the use of neurotoxins like BTX-A for treating conditions such as UVB-induced hyperpigmentation, specifically melasma, is an emerging area of interest, it is not yet a widely recognized treatment for this dermatologic condition. This literature review serves to provide a consolidated overview of the current therapeutic implications of BTX-A treatment for melasma and explore its proposed mechanisms of action. This review aims to provide a comprehensive analysis of the current evidence base for the efficacy of BTX-A treatment on melasma. To gain a comprehensive understanding on the current theories regarding BTX-A treatment on melasma, a literature review was conducted on all the available information using PubMed. A combination of keywords was used to maximize the search results, including "botulinum toxin," "melasma," "melanogenesis," "neurotoxin," "cholinergic system," "BTX-A," and "UV-induced melasma." The search was not restricted by date, allowing for the inclusion of articles offering historical context and those providing the most recent findings. Ninety-eight articles were reviewed to provide a consolidated update on the effectiveness of botulinum toxin A in reducing the appearance of melasma and potential mechanisms of action involved in doing so. Melasma is a challenging dermatologic condition due to its chronicity and various intrinsic and extrinsic factors that influence its pathogenesis. While current treatment options for melasma include topical, oral, and light-based therapies, recent studies suggest that BTX-A may hold potential as a viable treatment modality for melasma. Despite the mechanism of action remaining unclear, it is hypothesized that BTX-A inhibition of Ach receptors on melanocytes could play a role in the reduction of melanogenesis. BTX-A treatment in melasma-affected skin demonstrates statistically significant reduction in hyperpigmented lesions associated with melasma.

Clinical Evidence Regarding Spermidine–Hyaluronate Gel as a Novel Therapeutic Strategy in Vestibulodynia Management

Background: Vestibulodynia (VBD) represents a summation and overlapping of trigger factors (infections, hormonal disturbances, allergies, genetic aspects, psychological vulnerability, and others) with broad individual variability. As there are no standard treatment options for VBD, the disease is still in need of appropriate therapeutic tools. Objectives: A prospective observational trial was performed to confirm the efficacy of a topical gel containing a spermidine–hyaluronate complex (UBIGEL donna™) as either a stand-alone or companion treatment through a multicenter study on a large sample population. Methods: For women with VBD (n = 154), the treatment consisted of approximately two months (4 + 4 weeks) of applications according to the posology of UBIGEL. Evaluation of symptoms was performed on relevant clinical endpoints: dyspareunia and vulvovaginal pain/burning by a visual scale (VAS); vestibular trophism by a vestibular trophic health (VeTH) score; vulvoscopy through a cotton swab test; and the level of hypertonic pelvic floor by a physical graded assessment of levator ani hypertonus. Results: A total of 154 patients treated with UBIGEL donna™ showed significant improvements across all five evaluated parameters, including pain, dyspareunia, swab test results, muscle hypertonicity, and vestibular trophism. Pain and dyspareunia scores decreased by 46.5% and 33.5%, respectively, while significant improvements were also observed in the other parameters (p &lt; 0.0001). These improvements were consistent across various stratifications, including age and disease duration. Conclusions: The findings of the present study suggest that UBIGEL donna™ is effective in alleviating pain and dyspareunia, as well as reducing vestibular hypersensitivity in women with VBD. Although UBIGEL donna™ alone cannot serve as a comprehensive substitute for all recommended therapies, we suggest that multimodal therapy strategies may be crucial for attaining substantial improvement in any aspect of the condition.