High Safety Profile Research Articles

Comprehensive evaluation of the efficacy and safety of a new multi-component anti-aging topical eye cream.

The delicate periorbital region is susceptible to skin dehydration, wrinkles, and loss of elasticity. Thus, targeted and effective anti-aging interventions are necessary for the periorbital area. To evaluate the efficacy and safety of a new anti-aging eye cream formulated with the active complex (Yeast/rice fermentation filtrate, N-acetylneuraminic acid, palmityl tripeptide-1, and palmitoyl tetrapeptide-7). The cell viability and expressions of key extracellular matrix (ECM) components of the active complex were evaluated using a human skin fibroblast model. In the 12-week clinical trial, skin hydration, elasticity, facial photographs, and collagen density following eye cream application were assessed using Corneometer, Cutometer, VISIA, and ultrasound device, respectively. Dermatologists and participants evaluated clinical efficacy and safety at baseline, and after 4, 8, and 12weeks. PCR and immunofluorescent analyses revealed that the active complex significantly stimulated fibroblast proliferation (p<0.05) and markedly promote the synthesis of collagen and elastin. Clinical findings exhibited a substantial enhancement in skin hydration (28.12%), elasticity (18.81%), and collagen production (54.99%) following 12weeks of eye cream application. Dermatological evaluations and participants' assessments reported a significant improvement in skin moisture, roughness, elasticity, as well as fine lines and wrinkles by week 8. The new anti-aging eye cream, enriched with the active complex, demonstrates comprehensive rejuvenating effects, effectively addressing aging concerns in the periorbital area, coupled with a high safety profile.

The recombinant vaccine of Lactobacillus plantarum elicits immune protection against H1N1 and H9N2 influenza virus infection

Influenza A virus (IAV) causes annual epidemics and occasional pandemics, resulting in significant economic losses and numerous fatalities. Current vaccines, typically administered through injection, provide limited protection due to the frequent antigenic shift and drift of IAV strains. Therefore, the development of alternative broad-spectrum vaccine strategies is imperative. Lactic acid bacteria (LAB) represent promising candidates for vaccine engineering due to their low cost, high safety profile, and suitability for oral administration. In this study, we identified a strain of Lactobacillus plantarum (Lp) that is resistant to acid and bile salts and capable of colonizing the intestines of mice. Subsequently, we employed the RecE/T gene editing system to integrate headless hemagglutinins (mini-HA) into the genome of Lp, generating Lp-mini-HA-SP. Remarkably, immunization with Lp-mini-HA-SP elicited serum IgG antibody responses and conferred immune protection against H9N2 and H1N1 influenza virus challenges. Collectively, our findings offer a novel approach for the development of orally administered IAV vaccines and hold significant potential for future drug development endeavors.

Срединная кольпорафия как способ коррекции пролапса гениталий у пациенток пожилого и старческого возраста.

Introduction. The problem of genital prolapse (PG) remains relevant due to its high prevalence, reaching its maximum frequency in elderly women. When choosing surgical treatment of PG in the elderly and senile, it is necessary to take into account the presence of extragenital pathology and the somatic status of the patient. One of the methods of PG correction is median colporaphy, which has a high safety profile and a low recurrence rate. The aim of the study was to evaluate the results of median colporaphy in elderly and senile patients with genital prolapse. Materials and methods. The study included 40 women aged 65 years and older with symptomatic PG III-IV degree (POP-Q), who did not have sexual intercourse and did not seek it in the future, who underwent median colporaphy using the Lefor-Neugebauer technique in combination with colpoperineolevatoroplasty. The results of surgical treatment were evaluated according to the following criteria: duration of surgery, intra- and post- operative complications, assessment of the degree of PG before and after surgery, functional and anatomical results of surgery, duration of hospital stay, assessment of symptoms of PG before and after treatment. The follow-up period for patients is from 1 to 5 years after surgery. Results. The average duration of surgery is 41.5±9.6 minutes. The average volume of intraoperative blood loss was 55.5±20.1 ml. One intraoperative complication was registered – damage to the bladder wall. The average length of hospital stay is 5.6±1.0 days. No recurrence of PG was noted. Ac- cording to The Overactive Blade Questionnaire (OAB-q), there was an improvement in the average score from 9.9+6.0 to 7.3+2.7, which indicated a decrease in the severity of PG symptoms. The frequency of dysuric phenomena after surgery decreased by 2.2 times. Urinary disorders after surgery were detected in 15 (37.5%) patients; stress urinary incontinence – in 9 (22.5%) patients, in 6 (15.0%) – de novo, imperative urinary incontinence de novo – in 1 (2.5%) case. According to the Pelvic Floor Distress Inventory questionnaire (PFDI-20), there was a decrease in symptoms and func- tional disorders of the bladder and intestines in patients: a decrease in the number of points on the POPDI-6 scale from 62.1+18.9 to 1.4+3.7; CRAD-8 – from 18.0+14.8 points to 0.7+2.1; UDI-6 – from 29.9+23 to 7.1+10.2. According to an oral survey, all 40 (100%) patients would agree to undergo this operation again and not a single patient regretted the loss of sexual function. Conclusions. Median colporaphy is a safe and effective way to correct genital prolapse in elderly and senile women, including those with a burdened somatic status, who agree to give up vaginal intercourse. It is necessary to carefully inform patients about the irreversibility of vaginal obliteration and about the possible occurrence of dysuric phenomena after surgery.

Influence of regulatory peptides on neurogenic lower urinary tract dysfunction in multiple sclerosis. Data of one center

Objective: Cclinical evaluation of the effectiveness and safety of the effect of the regulatory polypeptide drug on neurogenic overactive bladder (OAB) in patients with multiple sclerosis (MS).Materials and methods: 41 patients with MS and urodynamically confirmed detrusor overactivity were included in a prospective, single-center, simple comparative clinical trial with sequential drug changes. The initial function of the lower urinary tract and its dynamic changes during therapy were studied by filling out a voiding diary and questionnaires using the EDSS, NBSS, SF-Qualiveen, I-QOL questionnaires. The control drug Solifenacin (patient group 1) is a specific competitive antagonist of muscarinic receptors of the M3 subtype, which causes detrusor contraction. The Study Drug (patient group 2) is a complex of regulatory polypeptides that have an organotropic effect on the bladder. Drug administration: control drug for 4 weeks, then an observation period of 4 weeks, after which - taking the Study Drug for 30 days. The results were monitored immediately after the end of taking the Study Drugs, after which they were compared with the initial data. Statistical analysis was carried out by the program “Statistica 10” (StatSoft Inc., USA), using non-parametric data analysis with median analysis, Wilcoxon test and Mann-Whitney U-test search. The results of differences were considered statistically significant if the probability of error was &lt;5% (p&lt;0.05).Results: Vvoiding diary: 14.6% and 24.4% of patients in groups 1 and 2, respectively, were freed from urinary incontinence; from nocturia —- 31.7% and 56.1% of patients for groups 1 and 2, respectively, the frequency of daily urination was normalized in 53.6% and 70.7% of patients in groups 1 and 2, respectively. NBSS questionnaire: decrease in the total questionnaire score by 29.2% and 47.4% for groups 1 and 2, respectively. SF-Qualiveen questionnaire: an increase in the overall assessment score by 42.3% for group 1 versus +66.5% for group 2. I-QOL questionnaire: improvement in quality of life by 56.0% and 80.4% for groups 1 and 2, respectively. The Study Drug has a higher safety profile compared to Solifenacin.Conclusion: Tthe effectiveness of the Study Drug in the correction of neurogenic OAB is higher in comparison with Solifenacin, which is reflected in a decrease in urgency, pollakiuria, the number of episodes of urinary incontinence and a significant improvement in the quality of life of these patients. The Study Drug demonstrates a high safety profile in the study.

Analysis of the Effect of Superselective Ophthalmic Artery Thrombolysis for Central Retinal Artery Occlusion

Introduction: The aim of the study was to investigate the clinical efficacy of superselective ophthalmic artery thrombolysis for central retinal artery occlusion (CRAO). Methods: Retrospective study of CRAO patients who attended the Department of Ophthalmology of Affiliated Hospital of Weifang Medical University from January 2022 to July 2023, 138 CRAO patients with onset time of 1–3 days were selected for the study. Among them, 86 patients refused thrombolytic treatment and chose to adopt traditional treatment, which was categorized as the control group; 52 patients adopted superselective ophthalmic artery thrombolytic treatment, which was categorized as the observation group. The visual acuity of the patients treated with traditional modality on the 4th day after the onset of the disease and the visual acuity of the patients treated with superselective ophthalmic artery thrombolysis on the 1st postoperative day were recorded, and the visual acuity improvement after different modalities of treatment was compared between the two groups. Results: In the control group, 77 (89.5%) of the treated patients had no improvement in visual acuity, 9 (10.5%) had improvement, 0 (0.0%) had significant improvement, and the total improvement was 9 (10.5%); in the observation group, 18 (34.6%) of the treated patients had no improvement in visual acuity, 21 (40.4%) had improvement, 13 (25.0%) had significant improvement, and the total improvement was 34 (65.4%). The total improvement rate of treatment in the observation group was 65.4%, which was significantly higher than the 10.5% in the control group, and the difference was statistically significant (p < 0.05). Conclusion: Superselective ophthalmic artery thrombolysis for patients with CRAO is clinically effective, promotes improvement in patient vision, and has a high safety profile.

Impact of thoracic paravertebral block and sufentanil on outcomes and postoperative cognitive dysfunction in thoracoscopic lung cancer surgery

BACKGROUND Postoperative pain management and cognitive function preservation are crucial for patients undergoing thoracoscopic surgery for lung cancer (LC). This is achieved using either a thoracic paravertebral block (TPVB) or sufentanil (SUF)-based multimodal analgesia. However, the efficacy and impact of their combined use on postoperative pain and postoperative cognitive dysfunction (POCD) remain unclear. AIM To explore the analgesic effect and the influence on POCD of TPVB combined with SUF-based multimodal analgesia in patients undergoing thoracoscopic radical resection for LC to help optimize postoperative pain management and improve patient outcomes. METHODS This retrospective analysis included 107 patients undergoing thoracoscopic radical resection for LC at The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital between May 2021 and January 2023. Patients receiving SUF-based multimodal analgesia (n = 50) and patients receiving TPVB + SUF-based multimodal analgesia (n = 57) were assigned to the control group and TPVB group, respectively. We compared the Ramsay Sedation Scale and visual analog scale (VAS) scores at rest and with cough between the two groups at 2, 12, and 24 h after surgery. Serum levels of epinephrine (E), angio-tensin II (Ang II), norepinephrine (NE), superoxide dismutase (SOD), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), tumor necrosis factor-α (TNF-α), and S-100 calcium-binding protein β (S-100β) were measured before and 24 h after surgery. The Mini-Mental State Examination (MMSE) was administered 1 day before surgery and at 3 and 5 days after surgery, and the occurrence of POCD was monitored for 5 days after surgery. Adverse reactions were also recorded. RESULTS There were no significant time point, between-group, and interaction effects in Ramsay sedation scores between the two groups (P &gt; 0.05). Significantly, there were notable time point effects, between-group differences, and interaction effects observed in VAS scores both at rest and with cough (P &lt; 0.05). The VAS scores at rest and with cough at 12 and 24 h after surgery were lower than those at 2 h after surgery and gradually decreased as postoperative time increased (P &lt; 0.05). The TPVB group had lower VAS scores than the control group at 2, 12, and 24 h after surgery (P &lt; 0.05). The MMSE scores at postoperative days 1 and 3 were markedly higher in the TPVB group than in the control group (P &lt; 0.05). The incidence of POCD was significantly lower in the TPVB group than in the control group within 5 days after surgery (P &lt; 0.05). Both groups had elevated serum E, Ang II, and NE and decreased serum SOD levels at 24 h after surgery compared with the preoperative levels, with better indices in the TPVB group (P &lt; 0.05). Marked elevations in serum levels of VEGF, TGF-β1, TNF-α, and S-100β were observed in both groups at 24 h after surgery, with lower levels in the TPVB group than in the control group (P &lt; 0.05). CONCLUSION TPVB combined with SUF-based multimodal analgesia further relieves pain in patients undergoing thoracoscopic radical surgery for LC, enhances analgesic effects, reduces postoperative stress response, and inhibits postoperative increases in serum VEGF, TGF-β1, TNF-α, and S-100β levels. This scheme also reduced POCD and had a high safety profile.

Cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs, manifested as urticaria and/or angioedema, anaphylaxis

BACKGROUND: The main mechanism of drug hypersensitivity to non-steroidal anti-inflammatory drugs is associated with inhibition of cyclooxygenase type 1, which leads to cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs from various subgroups of different chemical structures. Clinically, cross-hypersensitivity usually manifests in the form of urticaria and/or angioedema. AIM: To characterize a group of patients with cross-hypersensitivity to non-steroidal anti-inflammatory drugs manifesting as urticaria / angioedema / anaphylaxis. MATERIALS AND METHODS: To achieve this aim a prospective single-center study was conducted. Patients with a presumptive diagnosis of drug hypersensitivity to non-steroidal anti-inflammatory drugs (n=307) were consulted. A group of patients (n=237) with high probability of such reactions was identified, of which cross-hypersensitivity manifested as urticaria / angioedema / anaphylaxis was observed in 127 patients. This group was divided into 2 phenotypes: a group with concomitant chronic urticaria (n=67) and without it (n=60). We assessed demographic data, drug triggers, clinical manifestations, concomitant atopy, and compared these indicators between both groups. Selected patients underwent a drug provocation test with selective or predominantly selective non-steroidal anti-inflammatory drugs and paracetamol. RESULTS: Cross-hypersensitivity reactions manifested as urticaria / angioedema / anaphylaxis is the most common phenotype of immediate-type drug cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs (75.6%). Women develop this condition 2.5 times more frequently than men, and are more likely to develop cross-drug hypersensitivity with concomitant chronic urticaria with the onset of approximately 16 years later than men. Mild manifestations of cross-hypersensitivity (urticaria/angioedema) develop more frequently than severe ones (anaphylaxis). Angioedema in children, urticaria in adults with concomitant chronic urticaria and angioedema in adults without concomitant chronic urticaria are it's main manifestations. The most frequent non-steroidal anti-inflammatory drugs triggers are metamizole, acetylsalicylic acid and propionic acid derivatives. Non-steroidal anti-inflammatory drugs with the lowest risk of developing drug hypersensitivity are coxibs, paracetamol, and to a lesser extent ― meloxicam, nimesulide. CONCLUSION: The data obtained allowed us to expand our understanding of cross-hypersensitivity reactions to non-steroidal anti-inflammatory drugs presenting as urticaria/angioedema or anaphylaxis. Selective cyclooxygenase type 2 inhibitors and paracetamol are drugs with the highest safety profile.

Activated zinc pyrithione in topical treatment of atopic dermatitis: a case report

Atopic dermatitis is a systemic multifactorial genetically determined inflammatory skin condition characterized by an impairment of the epidermal barrier and Type 2 inflammation. Atopic dermatitis is highly prevalent, especially among children. Many authors consider atopic dermatitis as the initial stage of the atopic march, which typically manifests in the first year of life. Topical agents such as topical glucocorticosteroids and topical calcineurin inhibitors are the first-line treatments for atopic dermatitis. In recent years, there has been an increasing use of modern systemic anti-inflammatory agents, such as monoclonal antibodies and Janus kinase inhibitors. Therapy of patients with atopic dermatitis is aimed at relieving itching, improving skin barrier function, reducing inflammation, preventing skin infection and exacerbations. The effectiveness of treatment lies not only in improving the symptoms and quality of life of patients with atopic dermatitis, but also in preventing them from developing chronic or severe symptoms. Modern topical glucocorticosteroids and their combinations, have a proven high safety profile. However, available data on adverse events associated with their use often lead patients and their parents to develop a negative, phobic attitude towards treatment with these drugs. Zinc pyrithione, an activated form of zinc, is a safe and highly effective medication with anti-inflammatory, antifungal, and antibacterial properties. This article presents two clinical cases of moderate to severe atopic dermatitis in children, demonstrating the effectiveness of using activated zinc pyrithione in comprehensive therapy for this condition.

Effectiveness of Peripheral Antitussives in Patients with Dry Postinfectious Cough

Abstract Background: Postinfectious dry cough can significantly worsen the quality of life of patients, which forces them to seek medical help. To relieve this symptom, peripheral antitussive agents are most often used, since they have a high profile of effectiveness and safety. Subjects and Methods: The study used levodropropizine, which was prescribed to a study group consisting of 100 patients with dry postinfectious cough, at a dosage of 10 ml (60 mg) 3 times a day for 7 days. The comparison group consisted of 34 patients with dry postinfectious cough who refused to take levodropropizine or had contraindications to taking it. On the 1st, 4th, and 8th days of the study, complaints were collected, an objective examination, and an assessment of cough intensity using 6-point scales for evaluating day and night cough, as well as a Visual Analog Scale were conducted. In addition, undesirable side effects were assessed at each visit. Results: It was found that during 7 days of treatment with levodropropizine, the intensity of cough on the above-mentioned scales significantly decreased, and no side effects were observed in any patient. Conclusions: The resolution of the cough syndrome occurred faster when taking a peripheral antitussive drug (levodropropizine). Moreover, no side effects were reported in any of the subjects. Therefore, peripheral antitussives have a high efficacy and safety profile against dry postinfectious cough.

Hawthorn with "homology of medicine and food": a review of anticancer effects and mechanisms.

Over the past few years, there has been a gradual increase in the incidence of cancer, affecting individuals at younger ages. With its refractory nature and substantial fatality rate, cancer presents a notable peril to human existence and wellbeing. Hawthorn, a medicinal food homology plant belonging to the Crataegus genus in the Rosaceae family, holds great value in various applications. Due to its long history of medicinal use, notable effects, and high safety profile, hawthorn has garnered considerable attention and plays a crucial role in cancer treatment. Through the integration of modern network pharmacology technology and traditional Chinese medicine (TCM), a range of anticancer active ingredients in hawthorn have been predicted, identified, and analyzed. Studies have shown that ingredients such as vitexin, isoorientin, ursolic acid, and maslinic acid, along with hawthorn extracts, can effectively modulate cancer-related signaling pathways and manifest anticancer properties via diverse mechanisms. This review employs network pharmacology to excavate the potential anticancer properties of hawthorn. By systematically integrating literature across databases such as PubMed and CNKI, the review explores the bioactive ingredients with anticancer effects, underlying mechanisms and pathways, the synergistic effects of drug combinations, advancements in novel drug delivery systems, and ongoing clinical trials concerning hawthorn's anticancer properties. Furthermore, the review highlights the preventive health benefits of hawthorn in cancer prevention, offering valuable insights for clinical cancer treatment and the development of TCM with anticancer properties that can be used for both medicinal and edible purposes.

The PP2A inhibitor LB-100 mitigates lupus nephritis by suppressing tertiary lymphoid structure formation

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multi-organ involvement and autoantibody production. Patients with SLE face a substantial risk of developing lupus nephritis (LN), which imposes a substantial burden on both patients and their families. Protein phosphatase 2A (PP2A) is a widely distributed serine/threonine phosphatase that participates in regulating multiple signaling pathways. Inhibition of PP2A has been implicated in the treatment of various diseases. LB-100, a small molecule inhibitor of PP2A, has demonstrated anti-tumor therapeutic effects and high safety profile in preclinical experiments. However, the role of PP2A and its inhibitor has been insufficiently studied in LN. In this study, we assessed the potential effects of LB-100 in both MRL/lpr mice and R848-induced BALB/c mice. Our findings indicated that LB-100 administration led to reduced spleen enlargement, decreased deposition of immune complexes, ameliorated renal damage, and improved kidney function in both spontaneous and R848-induced lupus mouse models. Importantly, we observed the formation of tertiary lymphoid structures (TLSs) in the kidneys of two distinct lupus mouse models. The levels of signature genes of TLS were elevated in the kidneys of lupus mice, whereas LB-100 mitigated chemokine production and inhibited TLS formation. In addition, we confirmed that inhibition or knockdown of PP2A reduced the production of T cell-related chemokines by renal tubular epithelial cells (RTEC). In summary, our study highlighted the renal protective potential of the PP2A inhibitor LB-100 in two distinct lupus mouse models, suggesting its potential as a novel strategy for treating LN and other autoimmune diseases.

Erythrocyte-αPD-1 conjugates overcome resistance to checkpoint blockade immunotherapy: A first-in-human study.

2557 Background: While the immune checkpoint blockade (ICB) therapy has revolutionized the field of tumor therapy. the resistance remains a major challenge. We have previously developed WTX-212, an erythrocyte-antibody conjugate covalently linking anti-PD-1 antibody to erythrocyte membranes. Unlike conventional antibodies, WTX-212 exhibits natural accumulation in the spleen and remodels the splenic immune landscape in tumor-bearing mice. WTX-212 treatment efficiently activates CD8+ T cells in the spleen, which subsequently infiltrate into tumors and exhibit anti-tumor cytotoxicity. Additionally, activated T cells reduce the splenic reservoir of Myeloid-derived suppressor cells (MDSC) and those within tumors, further enhancing overall anti-tumor responses. Pre-clinical studies have demonstrated that WTX-212 can significantly suppress tumor growth in xenograft tumor models resistant to anti-PD-1 immunotherapies. A first-in-human (FIH) clinical trial is now investigating its potential in human cancer patients. Methods: The FIH trial (NCT05707325) is aimed to investigate the safety, pharmacokinetics and preliminary efficacy of WTX-212 in cancer patients with advanced malignancies. All of patients had previously received anti-PDs therapies and developed resistance to these treatments. By Feb 5th, 2024, the tumor lesions were assessed using RECIST v1.1 criteria. Blood and tumor samples were collected for correlative analysis. Results: 7 metastasized patients with various solid tumors, having undergone a median of 3.1 prior lines of therapy (ranging from 1-6), received WTX-212 monotherapy. None of patients treated with WTX-212 experienced treatment-related adverse events greater than Grade 3, indicating a high safety profile. WTX-212 was detectable in peripheral blood at the end of cycle in a dose dependent manner. Disease control was achieved in 5/7 patients (DCR=71%). Specifically, a patient with esophageal cancer, achieved a confirmed complete remission after 6-cycle treatment. Additionally, two patients, one with esophageal cancer (3L) and another with HPV-negative cervical cancer (4L), maintained stable disease for over 40 and 30 weeks, respectively. Consistent with our pre-clinical findings, a substantial reduction in MDSCs were observed in 6/7 patients (ranging from 24%-82%). Furthermore, a median 1.5-fold increase in T cells was noted in all patients in the peripheral blood after the 1st cycle of the treatment. Conclusions: WTX-212 treatment is safe and tolerable and shows promising clinical signs in cancer patients resistant to anti-PD-1 immunotherapy, supporting further investigation and exploration of WTX-212 monotherapy and combination therapy. Clinical trial information: NCT05707325 .

390P OriA362: A promising CLDN18.2/4-1BB bispecific antibody for targeting pancreatic and gastric cancers with high efficacy and safety profile

390P OriA362: A promising CLDN18.2/4-1BB bispecific antibody for targeting pancreatic and gastric cancers with high efficacy and safety profile

Endoscopic Ultrasound-Guided Liver Biopsy (EUS-LB): An Endoscopic Solution to the Unmet Needs of Liver Tissue Acquisition and Beyond

Abstract Aim and Objective Endoscopic ultrasound-guided liver biopsy (EUS-LB) is now increasingly being used across the globe as a method of liver tissue acquisition. This method is widely accepted by many professionals as it can overcome many shortcomings of percutaneous liver biopsy and transjugular liver biopsy. The aim of the study is to obtain the adequate and optimal biopsy rate associated with EUS-LB. Materials and Methods This is a retrospective observational study. Consecutive patients undergoing EUS-LB during the study period who were willing to consent were taken up for the study. Results Total 91 patients were taken up for the study. Median age of study population was 44 years out of which 39 patients were males and 52 were females (42.9 and 57.1%). Adequate biopsy rate (according to European Association for the Study of Liver Disease criteria) and optimal biopsy rate (according to American Association for the Study of Liver Diseases criteria) were 89 (81/91) and 60.4% (55/91), respectively. Rate of conclusive diagnosis was 95.6% (86/91). The commonest diagnosis encountered was nonalcoholic steatohepatitis) (23, 25.3%), followed by autoimmune hepatitis (17, 18.7%). Additional diagnostic information was obtained by endosonography during EUS-LB in 21 patients (23.1%). Gallstone disease was found in four (4.8%) patients, chronic calcific pancreatitis in two (1.9%) patients, significant abdominal lymphadenopathy defined as lymph node more than 1.5 cm in five (5.8%) patients, and esophageal or gastric varices in ten (10.6%) patients. One case of self-limiting biopsy site ooze was seen in EUS-LB and the patient was having cirrhosis. Conclusion This study showed a high diagnostic outcome and safety profile with EUS-LB technique. EUS-LB can achieve excellent histological yield when performed with optimal technique. Moreover, it is possible to obtain additional information during the procedure from diagnostic endosonography that is done as a part of EUS-LB.

Comparative observation of the effectiveness and safety of remimazolam besylate versus dexmedetomidine in gastrointestinal surgery in obese patients.

Surgery for obese patients carries a higher risk of anesthesia complications compared with surgery for nonobese patients. Thus, a safe and effective anesthesia strategy is necessary to improve the medical experience of such patients and ensure their safety. To compared the effectiveness and safety of remimazolam besylate versus dexmedetomidine (DEX) in gastrointestinal surgery in obese patients. The study cohort included 60 obese patients undergoing gastrointestinal surgery between July 2021 and April 2023, comprising 30 patients who received DEX intervention (control group) and 30 patients who received remimazolam besylate intervention (research group). Heart rate (HR), respiratory rate (RR), mean arterial pressure (MAP), blood oxygen saturation (SpO2), safety (nausea and vomiting, bradycardia, hypotension, and apnea), anesthesia and examination indices [induction time, anesthesia recovery time, and postanesthesia care unit (PACU) discharge time], sedation effect (Ramsay Sedation Scale), and postoperative pain visual analog scale were comparatively analyzed before anesthesia (T0), during anesthesia (T1), and after anesthesia (T2). At T1, the research group showed significantly smaller changes in HR, RR, MAP, and SpO2 than the control group, with a significantly lower adverse reaction rate and shorter induction, anesthesia recovery, and PACU discharge times. Additionally, the intra- and postoperative Ramsay Sedation Scale scores were statistically higher in the research group than in the control group. Remimazolam besylate was significantly more effective than DEX in gastrointestinal surgery in obese patients and had a higher safety profile and value in clinical promotion.

Advanced pulsed field ablation: comprehensive analysis of safety and efficacy in a real-world cohort

Abstract Background Pulsed field ablation (PFA) represents a novel energy modality for catheter ablation of atrial fibrillation (AF). Initial preclinical and clinical studies indicate a higher safety profile with promising efficacy outcomes as well as shorter procedure times. Real world data are sparce and methods to improve clinical success rates are under development. Methods In this observational study 124 patients underwent pulmonary vein isolation with PFA (Farapulse, Boston) for paroxysmal and persistent AF. For anatomical visualization and optimal positioning of the PFA catheter a 3D mapping system was used (Ensite X, Abbott). Patients were followed over a 15-month period to evaluate both efficacy and safety of PFA in a real-world cohort using an advanced mapping technology. Results The patient cohort had a mean age of 67 ± 11 years, 38% females (n= 47), paroxysmal AF 53% (n = 66), persistent AF 47% (n = 58). Acute pulmonary vein isolation (PVI) rate was 100%. After a median FU of 6 months, 17 patients (14%) had a recurrence of AF. In our study population no esophageal complications, pulmonary vein stenosis, or persistent phrenic palsy occurred. Major complications were observed in 2.4% of the cases (3/124), involving two pericardial tamponades (1.6%) and one vascular complication with intervention (0.8%). There were no stroke events and no occurrences of death. Noteworthy was the absence of complications such as coronary arterial spasm or hemolysis-related acute renal failure. The average dose-area product and average procedure time were 9.54 ± 7.68 µGym² and 57.94 ± 18 minutes, respectively. Conclusion PVI with PFA in a real world cohort demonstrates a high safety profile. Furthermore, high clinical success rates can be achieved also in mixed paroxysmal/persistent AF populations. The use of 3D mapping systems might even improve clinical outcomes of PVI with PFA and will also help to guide more complex ablation strategies in the future. These findings pave the way for further exploration into the long-term benefits and broader applicability of PFA in AF ablation.

Acute procedural characteristics and safety of pulsed field cryoablation for persistent AF: multicenter results from the first in human PARALELL trial

Abstract Introduction Pulsed Field Cryoablation (PFCA) is dual-energy cardiac ablation modality consisting of short-duration ultra-low temperature cryoablation (ULTC) followed immediately by pulsed electric field ablation (PFA) delivered from the same catheter. It has been hypothesized that it may be beneficial to combine the efficiency of PFA with the contact and stability offered by ULTC. In patients with persistent atrial fibrillation, PFCA could be of particular benefit when creating extended lesion sets beyond pulmonary vein isolation such as posterior wall ablation. By focusing the electric field in high-impedance frozen tissue, PFCA may increase lesion depth and durability despite lower delivered current, while minimizing PFA-related microbubbles and skeletal muscle contraction. Purpose To report the acute outcomes of PFCA observed in the first-in-human PARALELL trial. Methods PFCA was performed using a novel stylet-driven catheter connected to the dedicated ULTC and PFA energy sources. The protocol-defined lesion set included pulmonary vein isolation and posterior wall (PW) ablation, with additional left and right atrial targets per operator discretion. Circular and linear lesions of varying dimensions were created by in-vivo shaping of the flexible, 11 cm-long ablation element of the catheter using exchangeable stylets. The ULTC freeze of 30 second duration was followed immediately by bipolar, biphasic PFA pulse trains delivered sequentially between the pairs of sixteen 3-mm electrodes evenly spaced along the ablation element. Results At 5 European and Canadian sites, 26 patients (age 68±9 years, 88.5% male, median left atrial size 45 mm, IQR [43 mm-48 mm]) underwent PFCA with 22.6 ± 9.6 ablation lesions per patient. The lesion set included 11.9 ± 4.1 lesions to PVs, 7.4 ± 2.7 to the PW, and in 14 patients, 6.6 ± 9.0 lesions to other atrial targets (left atrial roof and floor, PV carinas, mitral and cavotricuspid isthmuses). Isolation was achieved in 94.2% (98 of 104) of PVs and 92.3% (24 of 26) of PWs. The average procedure time was 130.3 ± 40.9 minutes, with catheter dwell time of 78.8 ± 26.0 minutes. Procedure-related groin hematoma at discharge was the only serious adverse event by site adjudication. Intracardiac echocardiography (ICE) performed in 18 patients identified Grade I (FEW) microbubbles in 1.3% (5 of 398) of ablations. Similarly, only faint muscular contractions were observed in 2 of 26 patients, occurring during 1.2% (4 of 339) of lesions placed in 15 patients not receiving any paralytic agents. Conclusions This initial multi-center experience suggests that PFCA can be efficiently performed on multiple atrial targets using a single versatile catheter system, with high acute success and good early safety profile, including minimal occurrence of PFA-related microbubbles and skeletal muscle contractions. The evaluation of the chronic 12-month effectiveness vs ULTC benchmarks and PFA comparators is ongoing.

IDENTIFYING RISK FACTORS FOR TREATMENT FAILURE IN B-CELL CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS RECEIVING BENDAMUSTINE±RITUXIMAB THERAPY

Introduction. The initial assessment of prognosis is of particular importance in determining the management of patients with B-cell chronic lymphocytic leukemia and the choice of specific therapy. The aim is to analyze the risk factors for failure to achieve a complete response to the bendamustine±rituximab treatment regimen in patients with B-cell chronic lymphocytic leukemia. Materials and methods. Twenty-two patients undergoing treatment for B-cell chronic lymphocytic leukemia (B-CLL) progression were included in the study. Response to treatment was assessed on the 56th day, categorized as complete, partial, or no response. Patients were divided into three groups based on their response: group I (n=6) included patients who showed a complete response after receiving bendamustine±rituximab; group II (n=11) included patients who achieved a partial response; and group III (n=5) consisted of patients with no response. Risk factors for chemotherapy resistance, as well as general and biochemical blood counts, were evaluated and subjected to statistical analysis. Results: Stage III (C) and IV (C) according to the Rai, Binet classification were recorded in 33.2% of patients with a complete response to chemotherapy, in 36.4% of patients with a partial response to chemotherapy, and in 60% of patients with no response to specific treatment. A decrease in hemoglobin level below 100 g/L was recorded only in patients with a partial response and no response, namely in 4 (36%) patients of group II and 1 (20%) patient of group III. On day 56, in patients of group II who received a partial response, there was a direct correlation between the level of leukocytes in the hemogram and the activity of aspartate aminotransferase (r=0.71; p=0.01) and the content of total bilirubin (r=0.63; p=0.03) in the biochemical blood test. After 2 courses of chemotherapy in patients of group III, a direct correlation of high strength between the level of leukocytes in the hemogram and the activity of aspartate aminotransferase (r=0.93; p=0.02) and alanine aminotransferase (r=0.93; p=0.02) in the biochemical blood test was found. The bendamustine±rituximab chemotherapy regimen has a high safety profile.

Advancing vaccine development: Evaluation of a mannose-modified lipid nanoparticle-based candidate for African swine fever p30 mRNA vaccine eliciting robust immune response in mice

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).

Therapeutic effectiveness analysis of tenofovir alafenamide and tenofovir disoproxil fumarate on the treatment for chronic hepatitis B.

To explore the therapeutic effectiveness of tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF) on the treatment for chronic hepatitis B (CHB). Retrospectively analyzing 241 cases of chronic hepatitis B patients admitted to our hospital from January 2020 to December 2021, they were divided into a TAF group of 180 cases and a TDF group of 61 cases. The liver function, serum virus markers, clinical efficacy, adverse reactions and cost-effectiveness ratio (CER) analysis of 2 groups were compared. Two groups of patients had no statistically significant difference in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) before treatment. After treatment, the levels of ALT, AST and TBIL were lower than before treatment in both groups (P < .05), but the inter-group difference was not statistically significant (P > .05). After treatment, Hepatitis B surface antigen (HBsAg) conversion rate and Hepatitis B virus DNA (HBV-DNA) conversion rate in the 2 groups had no statistically significant difference. After treatment, the difference in total clinical cure rate between the 2 groups has no statistical significance (P > .05), adverse reactions rate of TAF group was lower than that of TDF group (P < .05). The drug cost median of TAF group was higher than that of TDF (P < .05), but Cost-effectiveness analysis showed the CER of TAF group was similar of TDF group. TAF or TDF therapy can both improve liver function and promote recovery in patients with CHB, achieving the goal of treatment. TAF have more cost but have similar CER to TDF. Moreover, TAF therapy has a higher safety profile.