High Safety Profile Research Articles

Enhancing Fc-mediated effector functions of monoclonal antibodies: The example of HexaBodies.

Since the approval of the CD20-targeting monoclonal antibody (mAb) rituximab for the treatment of lymphoma in 1997, mAb therapy has significantly transformed cancer treatment. With over 90 FDA-approved mAbs for the treatment of various hematological and solid cancers, modern cancer treatment relies heavily on these therapies. The overwhelming success of mAbs as cancer therapeutics is attributed to their broad applicability, high safety profile, and precise targeting of cancer-associated surface antigens. Furthermore, mAbs can induce various anti-tumor cytotoxic effector mechanisms including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), all of which are mediated via their fragment crystallizable (Fc) domain. Over the past decades, these effector mechanisms have been substantially improved through Fc domain engineering. In this review, we will outline the different approaches to enhance Fc effector functions via Fc engineering of mAbs, with a specific emphasis on the so-called "HexaBody" technology, which is designed to enhance the hexamerization of mAbs on the target cell surface, thereby inducing greater complement activation, CDC, and receptor clustering. The review will summarize the development, preclinical, and clinical testing of several HexaBodies designed for the treatment of B-cell malignancies, as well as the potential use of the HexaBody technology beyond Fc-mediated effector functions.

Natural Plant Materials as a Source of Neuroprotective Peptides.

In many circumstances, some crucial elements of the neuronal defense system fail, slowly leading to neurodegenerative diseases. Activating this natural process by administering exogenous agents to counteract unfavourable changes seems promising. Therefore, looking for neuroprotective therapeutics, we have to focus on compounds that inhibit the primary mechanisms leading to neuronal injuries, e.g., apoptosis, excitotoxicity, oxidative stress, and inflammation. Among many compounds considered neuroprotective agents, protein hydrolysates and peptides derived from natural materials or their synthetic analogues are good candidates. They have several advantages, such as high selectivity and biological activity, a broad range of targets, and high safety profile. This review aims to provide biological activities, the mechanism of action and the functional properties of plant-derived protein hydrolysates and peptides. We focused on their significant role in human health by affecting the nervous system and having neuroprotective and brain-boosting properties, leading to memory and cognitive improving activities. We hope our observation may guide the evaluation of novel peptides with potential neuroprotective effects. Research into neuroprotective peptides may find application in different sectors as ingredients in functional foods or pharmaceuticals to improve human health and prevent diseases.

RNA-Activatable Near-Infrared Photosensitizer for Cancer Therapy.

Photodynamic therapy (PDT) has recently come to the forefront as an exceptionally powerful and promising method for the treatment of cancer. Existing photosensitizers are predominantly engineered to target diverse biomolecules, including proteins, DNA, lipids, and carbohydrates, and have proven to greatly enhance the efficacy or specificity of PDT. However, it is noteworthy that there exists a conspicuous scarcity of photosensitizers specifically designed to target RNAs. Recognizing the crucial and multifaceted roles played by RNAs in various cellular processes and disease states, we have ventured into the development of a novel RNA-targeting photosensitizer, named Se-718, designed specifically for PDT-based cancer therapy. Se-718 has been engineered to exhibit a high molar absorption coefficient in the NIR region, which is crucial for effective PDT. More importantly, Se-718 has demonstrated a distinct RNA-targeting capability, as evidenced through rigorous testing in both circular dichroism and fluorescence experiments. Furthermore, Se-718 has been shown to display both type I and type II photodynamic properties. This unique characteristic enables the efficient killing of cancer cells under a wide range of oxygen conditions, both normoxic (21% O2) and hypoxic (2% O2). The IC50 of Se-718 can be as low as 100 nM, and its light-to-dark toxicity ratio is an impressive 215 times higher, outperforming most photosensitizers currently available. Moreover, in vivo studies conducted with tumor-bearing mice have demonstrated the excellent antitumor effects and high safety profile of Se-718. Considering the outstanding PDT efficacy of Se-718, we are optimistic that the development of RNA-targeting photosensitizers may provide an innovative and highly effective option for cancer therapeutics in the near future.

The highly stabilized biologically derived peptide VIESPPEI alleviates DSS-induced colitis in mice by preventing colonic atrophy and modulating gut microbiota

Ulcerative colitis (UC) is a recurrent gastrointestinal infection within the spectrum of inflammatory bowel disease, posing risks associated with long-term medication. Consequently, this study aimed to investigate the effects of novel duck liver protein-derived bioactive peptides, characterized by a higher safety profile, on dextran sulfate sodium (DSS)-induced colitis in mice. The results indicated that the retention rate of VIESPPEI remained above 80% following simulated gastrointestinal digestion in vitro, demonstrating strong stability and practical application potential. The peptide VIESPPEI was found to alleviate weight loss in colitis-afflicted mice, inhibit the elevation of the disease activity index (DAI), and significantly improve symptoms such as atrophy and shortening of the colon. Histological examination further confirmed that VIESPPEI intake promoted the recovery of acute colitis in mice. Additionally, it significantly reduced myeloperoxidase activity and increased superoxide dismutase and catalase activities in the colon tissues of UC mice. Notably, a substantial increase in beneficial gut microbiota and the populations of three beneficial bacteria species (Anaplasma spp., Tannabacterium spp., and Bifidobacterium spp.) that produce short-chain fatty acids, along with a decrease in pathogenic groups such as Streptococcus and Turicibacter, may account for the improvement in colitis observed in UC mice treated with VIESPPEI. This study provides new evidence that VIESPPEI alleviates UC and provides a theoretical basis for the development of functional peptide beverages.

Prior coronary stent does not exclude major pulmonary resection regardless of antiplatelet therapy.

We assessed the safety of general thoracic surgery in patients with prior coronary stents undergoing lung resection, based on differences in perioperative antiplatelet therapy management. We retrospectively examined 150 patients with coronary artery stents who underwent pulmonary resection between July 2009 and July 2018. The impact of the antiplatelet agent on thoracic surgery safety was assessed by comparing perioperative outcomes, including major adverse cardiac and cerebrovascular events, among the discontinued antiplatelet therapy (group D), heparin bridging (group H), and continuous antiplatelet therapy (group C) groups. Groups D, H, and C included twenty-four, eighty-four, and forty-two patients, respectively. Second-generation drug-eluting stents were used in > 50% of the patients. No significant differences were found in the estimated blood loss, transfusion rate, or operative duration. Major adverse cardiac and cerebrovascular events occurred in four (2.7%) patients, which was comparable among the groups. In group H, postoperative heart failure and transient ischemic attack with stroke occurred in one patient each. Major bleeding occurred in two (4.7%) patients in group C. Pulmonary resection surgical outcomes in patients with coronary artery stents were feasible regardless of antiplatelet therapy continuation. However, discontinuing dual-antiplatelet or single-antiplatelet therapy in such patients may be reasonable because this generation of drug-eluting stents has a higher safety profile than bare-metal and first-generation drug-eluting stents.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

Methylene Blue Reduces Electroretinogram Distortion and Ganglion Cell Death in a Rat Model of Glaucoma.

Glaucoma is the second leading cause of blindness worldwide and is, in most cases, a consequence of elevated intraocular pressure (IOP), ultimately resulting in the death of retinal ganglion cells (RGCs). Current treatments are mostly focused on normalizing IOP, but we propose the additional use of neuroprotective agents, including methylene blue (MB), to block the loss of RGCs. Wistar rats were subjected to episcleral vein cauterization (EVC) in the left eye while the right eye was sham-operated. One week later, they were divided into two groups, which were injected with either 2.0 mg/kg MB or phosphate-buffered saline (PBS), twice a day, for 7 days. Fifteen days after surgery, rats were tested with scotopic electroretinography (ERG) or pattern electroretinography (PERG). After sacrifice, the number of RGCs and the thickness of the inner retina (IR) were evaluated both in the peripheral and central areas of the retina. Scotopic ERG showed a marked reduction (p < 0.0001) on the a- and b-wave amplitude and oscillatory potential (OP) complexity of the eyes subjected to EVC. These parameters were significantly (p < 0.01) restored by the application of MB. PERG indicated that EVC was responsible for a very significant decrease in N2 amplitude (p < 0.0001) and prolongation of N2 implicit time (p < 0.0001). Treatment with MB significantly restored N2 amplitude (p < 0.0001). In parallel with the ERG results, morphological analysis showed a significant loss of RGCs (p < 0.0001) and IR thickness (p < 0.0001) in both the peripheral and central retinas subjected to EVC, which was significantly prevented (p < 0.0001) by MB treatment. We have shown that MB treatment can be effective in preventing physiological and morphological hallmarks of optic neuropathy in a model of ocular hypertension, which faithfully recapitulates human open-angle glaucoma. Due to its high safety profile, this drug could therefore represent a new pharmacologic strategy to prevent vision loss in glaucoma patients.

The Keystone Flap: A Game Changer That Promises New Horizons in Reconstructive Surgery.

Since its first description emerged in 2003, the keystone flap has garnered the attention of the international scientific community due to its high safety profile and the suitably low complication rate associated with the reconstructive process. In this study, data were obtained from the performance of 72 keystone flaps to cover soft-tissue defects after the excision of neoplastic processes, excisions, and injuries occurring in polytrauma. The study was conducted in the Department of Plastic Surgery, "Bagdasar-Arseni" Emergency Hospital, Bucharest, and two plastic surgeons in the department performed the surgical procedures. The statistical analysis revealed a remarkably low complication rate (3.22%), excellent functional and esthetic results, and a short hospitalization time. No intraoperative complications were identified during this study. The degree of satisfaction obtained after reconstructive surgery was exceptionally high, with a score of 9.47 on a 10-point rating scale (0 = poor results, 10 = excellent results) from the patient's perspective and 9.51 out of 10 for the surgical team. The keystone flap is the optimal solution for reconstructing soft-tissue defects of variable sizes and shapes. It is associated with a low length of hospitalization, a low complication rate, and high patient satisfaction.

Network pharmacology prediction and molecular docking analysis on the mechanism of eugenol as a candidate against estrogen receptor-positive breast cancer

Context: Breast cancer therapy currently presents several uncomfortable side effects in patients, including effects on non-malignant tissues, recurrence, and resistance, which restrict their utilization. Consequently, researchers have directed their attention toward studying plant-derived anticancer compounds that exhibit high efficacy and safety profiles. Eugenol, a major component found in clove plants, demonstrates promising potential as a therapeutic agent for both estrogen receptor-positive and estrogen receptor-negative breast cancer. Aims: To predict the target of eugenol in estrogen receptor–positive breast cancer using network pharmacology and molecular docking analyses. Methods: Network pharmacology analysis was performed using the Chemical Toxigenomic Database, STITCH, GeneCards, Cytoscape, Enrichr, and Stringdb. Subsequently, molecular docking was performed using protein targets obtained from the RCSB-PDB and analyzed using AutoDock software. Results: Network pharmacology study and molecular docking revealed the anticancer effect of eugenol against breast cancer estrogen receptor–positive, especially in cancer and apoptotic pathways, by acting on caspase-3 (CASP3), epidermal growth factor receptor (EGFR), and poly [ADP-ribose] polymerase 1 (PARP1) signaling pathways. The docking results between the protein targets and eugenol showed that eugenol has the strongest binding with CASP3 (ligand binding energy: -5.78 kcal/mol), followed by eugenol binding with EGFR (ligand binding energy: -5.58 kcal/mol), and eugenol binding with PARP1 (ligand binding energy: -5.58 kcal/mol). Conclusions: Eugenol is a potential candidate for breast cancer therapy, especially for apoptosis mediated by CASP3 in breast cancer luminal A.

Oral Fenbendazole for Cancer Therapy in Humans and Animals.

Fenbendazole is a benzimidazole anthelmintic agent commonly used to treat animal parasitic infections. In humans, other benzimidazoles, such as mebendazole and albendazole, are used as antiparasitic agents. Since fenbendazole is not currently approved by the FDA or EMA, its pharmacokinetics and safety in humans have yet to be well-documented in medical literature. Despite this, insights can be drawn from existing in vitro and in vivo animal studies on its pharmacokinetics. Given the low cost of fenbendazole, its high safety profile, accessibility, and unique anti-proliferative activities, fenbendazole would be the preferred benzimidazole compound to treat cancer. To ensure patient safety in the repurposing use of fenbendazole, it is crucial to perform clinical trials to assess its potential anticancer effects, optimal doses, therapeutic regimen, and tolerance profiles. This review focuses on the pharmacokinetics of orally administered fenbendazole and its promising anticancer biological activities, such as inhibiting glycolysis, down-regulating glucose uptake, inducing oxidative stress, and enhancing apoptosis in published experimental studies. Additionally, we evaluated the toxicity profile of fenbendazole and discussed possibilities for improving the bioavailability of the drug, enhancing its efficacy, and reducing potential toxicity.

May Patients with Recurrent Venous Disease Benefit from Sequential Treatment More than Those without Previous Intervention? A Single-Center Retrospective Study on the Safety and Efficacy of Abdominal and Pelvic Veins Embolization in Sequential Approach.

Background/Objective: The endovenous embolization of insufficient abdominal/pelvic veins is the preferred method of treatment. Also, it seems to be crucial in the treatment of lower limb vein insufficiency, particularly in recurrent disease. This study aimed to evaluate of pelvic vein embolization safety and its impact on the short-term outcome in the sequential treatment of venous disease. Methods: A retrospective analysis involved data from 506 female patients with venous disease involving abdominal and pelvic veins. All records were extracted from the medical database and included patient history, imaging reports as well as pre- and post-operative surveys. Results: Among the patients analyzed, 37.2% underwent some venous intervention in the past, with significant differences in symptom severity between groups. The embolization procedure revealed a high safety profile, with no serious complications. Pain during and after the procedure was generally low, with significantly lower pain scores in patients with recurrence. In patients who required left renal vein venoplasty a 1.7-fold increased risk of lumbar pain after embolization and venoplasty procedure was observed. Overall, 66.6% of patients reported improvement in pelvic symptoms and 72.1% experienced improvement in leg symptoms. The full sequential treatment protocol (abdominal, pelvic, and leg compartment) demonstrated superior outcomes in leg symptom improvement compared to embolization alone. Conclusions: Pelvic vein embolization is a safe and effective method of treatment, significantly improving both pelvic and leg symptoms, particularly in patients with a history of previous interventions in lower limb veins. Further studies are warranted to validate our findings and further refine treatment protocols.

Neuron-Derived Extracellular Vesicles miRNA Profiles Identify Children Who Experience Adverse Events after Ketamine Administration for Procedural Sedation.

Ketamine provides the highest safety profile among sedatives for procedural sedation and analgesia in the pediatric emergency setting. However, it can cause vomiting and recovery agitation. No studies have examined epigenetic factors, such as microRNAs, for predicting the occurrence of these adverse events. Neuronal-derived extracellular vesicle microRNA profiles were studied to predict the occurrence of ketamine-induced vomiting and recovery agitation in children. For this aim, a single-center prospective pharmacoepigenetic study was performed and 50 children who underwent procedural sedation with intravenous ketamine as the only sedative drug were enrolled between October 2019 and November 2022. MiRNA profiling in plasma neural-derived extracellular vesicles was analyzed through next-generation sequencing and measured before treatment with ketamine. Twenty-two patients experienced vomiting or recovery agitation. Among the 16 differentially expressed microRNAs, the upregulated miR-15a-5p and miR-484 targeted genes related to N-methyl-D-aspartate (NMDA) receptor activity, including glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A). Preliminary data confirmed lower GRIN2A levels in patients who developed these events. Downregulated miR-126-3p and miR-24-3p targeted AMPA receptor-associated genes. Functional analyses of gene targets revealed the enrichment of glutamatergic and neurotrophins signaling. Recovery agitation was associated with this network. Vomiting was related to dopaminergic and cholinergic systems. Three miRNAs (miR-18a-3p, miR-484, and miR-548az-5p) were identified as predictive biomarkers (AUC 0.814; 95% CI: 0.632-0.956) for ketamine-induced vomiting and recovery agitation. MicroRNA profiles can predict the development of ketamine-induced vomiting or recovery agitation in children. This study contributes to the understanding of the mechanisms underlying ketamine-induced adverse events.

The Experience of a Tertiary Referral Center with Endoscopic Management and Combining Percutaneous Intervention for the Treatment of Walled-Off Necrosis: A Stepwise Approach

Background: This study aimed to assess the effectiveness and safety of endoscopic management in patients with walled-off necrosis and additionally explore the results of a stepwise approach for combining percutaneous intervention in cases where endoscopic management was inadequate. Methods: We included cases of endoscopic management for walled-off necrosis between February 2019 and December 2023. Results: Endoscopic management was performed in 11 patients. The median largest dimension was 150 mm. Multiple cavities were present in four patients. Technical success was 90.9%, while clinical success with only endoscopic management was 36.3%. Clinical success could not be achieved with only endoscopic management in patients with a large diameter (≥125 mm) or multi-lobulated walled-off necrosis. Combining percutaneous intervention resulted in success for all patients. Two patients experienced major complications: one suffered from major bleeding, while the other experienced perforation, necessitating surgical intervention. The patient with perforation died due to multi-organ failure. Conclusions: Endoscopic management is recommended as the primary treatment method for walled-off necrosis due to its less invasive and higher safety profile. In cases involving large or multi-lobulated walled-off necrosis where clinical success cannot be achieved, combining percutaneous intervention is highly successful and safe. Ultimately, this approach can minimize the need for more invasive surgery.

Photobiomodulation Therapy for Improvement of Body Contour: A Retrospective Study on Middle Eastern Participants.

The rising demand for body contouring and concerns about side effects of invasive surgical procedures have led to advances in providing new non-invasive alternative methods for weight reduction. The current retrospective study investigated the safety and efficacy of photobiomodulation technology in reducing local obesity in Middle Eastern participants. Providing data about body circumferences of 30 participants, with body mass index (BMI) >28 and localized obesity in the abdomen, thighs, buttocks, or arms were included in the final data synthesis. All the records were received at least 4 treatment sessions with the photobiomodulation technology (Volcano device) in Center for Research and training in Skin Diseases and Leprosy (CRTSDL) during June 2022-September 2022 Reductions in body standing circumferences as well as reported adverse effects and participants' satisfaction were retrospectively evaluated and reported. . The extricated data included 30 females participants aged 42.06 ± 11.6 years and localized obesity in the abdomen (15 cases), thighs (7 cases), hip (one case) and arms (7 cases). While BMIs were not significantly different from the baseline, abdominal, arm and tight circumferences showed a significant decline after receiving 4 and 6 treatment sessions (P<0.01).. There was no report of adverse effect and overall satisfaction was an "excellent" grade. This study demonstrated the effectiveness and safety of photobiomodulation in reduction of circumferential size in abdomen, buttock, thigh, and arm areas in Middle Eastern participants with high patient satisfaction and acceptable safety profile.

Experimental Human Pneumococcal Carriage using Streptococcus pneumoniae serotype 3 in Malawi: a dose ranging and reproducibility human infection study

Background Streptococcus pneumoniae is a major cause of morbidity and mortality from respiratory tract infections, pneumonia, meningitis, and sepsis. Nasopharyngeal carriage of pneumococcus is a prerequisite for pneumococcal disease and transmission. Since the global introduction of pneumococcal conjugated vaccines, rates of pneumococcal disease have declined for many vaccine type serotypes but serotype 3 (SPN3) continues to cause significant disease. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation, understanding the impact of colonisation on acquired immunity and for testing pneumococcal vaccines. This study will develop a serotype 3 EHPC model to address some pertinent questions on the burden of pneumococcal disease in Malawi. Methods Healthy adults aged 18-50 years will be recruited, with a maximum target of 83 participants to complete all study visits. The study will consist of a dose ranging and safety study, followed by a reproducibility study. Sequential cohorts of 10 healthy participants will be challenged with escalating doses of SPN3 in the dose ranging study. Samples will be collected before inoculation and on days 2, 7, 13, 16, 21 and 28 following inoculations, for determination of carriage. A total of 33 participants will be enrolled in the reproducibility part and will use a dose that established ≥60% of carriage, and with a high safety profile. Samples will be collected for determination of both local and systemic immunological responses to pneumococcal challenge. Upon completion of study visits, participants will complete a questionnaire establish acceptability. Interpretations We expect to establish an optimal SPN3 dose required to establish nasopharyngeal colonisation in healthy adults in an EHPC model. The model can then be used to evaluate pneumococcal vaccines in both healthy and at-risk populations.

Trematocine-derived antimicrobial peptides from the Antarctic fish Trematomus bernacchaii: potent antibacterial agents against ESKAPE pathogens.

This study investigated the interaction with membrane mimetic systems (LUVs), bacterial membranes, the CD spectra, and the bactericidal activity of two designed trematocine mutants, named Trem-HK and Trem-HSK. Mutants were constructed from the scaffold of Trematocine (Trem), a natural 22-amino acid AMP from the Antarctic fish Trematomus bernacchii, aiming to increase their positive charge. The selectivity of the designed AMPs towards bacterial membranes was improved compared to Trematocine, verified by their interaction with different LUVs and their membranolytic activity. Additionally, their α-helical conformation was not influenced by the amino acid substitutions. Our findings revealed a significant enhancement in antibacterial efficacy against ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacteriaceae family) pathogens for both Trem-HK and Trem-HSK. Firstly, we showed that the selectivity of the two new designed AMPs towards bacterial membranes was greatly improved compared to Trematocine, verifying their interaction with different LUVs and their membranolytic activity. We determined that their α-helical conformation was not influenced by the amino acid substitutions. We characterized the tested bacterial collection for resistance traits to different classes of antibiotics. The minimum inhibitory and bactericidal concentration (MIC and MBC) values of the ESKAPE collection were reduced by up to 80% compared to Trematocine. The bactericidal concentrations of Trematocine mutants showed important membranolytic action, evident by scanning electron microscopy, on all tested species. We further evaluated the cytotoxicity and hemolytic activity of the mutants. At 2.5 μM concentration, both mutants demonstrated low cytotoxicity and hemolysis, indicating selectivity towards bacterial cells. However, these effects increased at higher concentrations. Assessment of in vivo toxicity using the Galleria mellonella model revealed no adverse effects in larvae treated with both mutants, even at concentrations up to 20 times higher than the lowest MIC observed for Acinetobacter baumannii, suggesting a high potential safety profile for the mutants. This study highlights the significant improvement in antibacterial efficacy achieved by increasing the positive charge of Trem-HK and Trem-HSK. This improvement was reached at the cost of reduced biocompatibility. Further research is necessary to optimize the balance between efficacy and safety for these promising AMPs.

Anticoccidial activity of a botanical natural product based on eucalyptus, apigenin and eugenol against Eimeria tenella in broiler chickens

BackgroundChicken coccidiosis is an intracellular parasitic disease that presents major challenges to the development of the commercial poultry industry. Perennial drug selective pressure has led to the multi-drug resistance of chicken coccidia, which makes the prevention and control of chicken coccidiosis extremely difficult. In recent years, natural plant products have attracted the attention of researchers due to their inherent advantages, such as the absence of veterinary drug residues. The development of these natural products provides a new direction for the prevention and treatment of chicken coccidiosis.MethodsThe anticoccidial effect of a natural plant product combination formulation (eucalyptus oil + apigenin + eugenol essential oil) was tested against Eimeria tenella in broilers. To search for the optimal concentration of the combination formulation, we screened 120 broilers in a chicken cage trial in which 100 broilers were infected with 5 × 104 sporulated Eimeria tenella oocysts; broilers receiving a decoquinate solution was set up as a chemical control. The optimal anticoccidial concentration was determined by calculating the anticoccidial index (ACI), and the suitable concentration was used as the recommended dose for a series of safety dose assessment tests, such as feed conversion ratio (FCR), hematological indices and serum biochemical indices, as well as liver and kidney sections, at onefold (low dose), threefold (medium dose) and sixfold (high dose) the recommended dose (RD).ResultsThe results showed that this combination formulation of three plant natural products had a better anticoccidial effect than formulations containing two plant natural products or a single one, with an ACI of 169.3. The dose gradient anticoccidial test revealed that the high-dose formulation group had a better anticoccidial effect (ACI = 169.2) than the medium- and low-dose groups. The safety evaluation test showed that concentrations of the formulation at one-, three- and sixfold the RD were non-toxic to Arbor Acres broilers, indicating the high safety of the combination formulation.ConclusionsThe combination formulation showed not only a moderate anticoccidial effect but also had a high safety profile for broilers. The results of this study indicate a new alternative for the prevention and control of coccidiosis in broilers.Graphical

Outcome of intradiscal condoliase injection therapy for patients with recurrent lumbar disc herniation.

Retrospective cohort study. This study aimed to compare data from patients who received intradiscal condoliase (chondroitin sulfate ABC endolyase) injection for primary lumbar disc herniation (LDH) and recurrent LDH. Chemonucleolysis with condoliase for LDH is a treatment with relatively good results and a high safety profile; however, few studies have reported recurrence after LDH surgery. The study participants were 249 patients who underwent intradiscal condoliase injection for LDH at nine participating institutions, including 241 patients with initial LDH (group C) and eight with recurrent LDH (group R). Patient characteristics including age, sex, body mass index, disease duration, intervertebral LDH level, smoking history, and diabetes history were evaluated. Low back pain/leg pain Numerical Rating Scale (NRS) scores and the Oswestry Disability Index (ODI) were used to evaluate clinical symptoms before treatment and at 6 months and 1 year after treatment. Low back pain NRS scores (before treatment and at 6 months and 1 year after treatment, respectively) in group C (4.9 → 2.6 → 1.8) showed significant improvement until 1 year after treatment. Although a tendency for improvement was observed in group R (3.5 → 2.8 → 2.2), no significant difference was noted. Groups C (6.6 → 2.4 → 1.4) and R (7.0 → 3.1 → 3.2) showed significant improvement in the leg pain NRS scores after treatment. Group C (41.4 → 19.5 → 13.7) demonstrated significant improvement in the ODI up to 1 year after treatment; however, no significant difference was found in group R (35.7 → 31.7 → 26.4). Although intradiscal condoliase injection is less effective for LDH recurrence than for initial cases, it is useful for improving leg pain and can be considered a minimally invasive and safe treatment method.

Long-Term Efficacy and Safety of Stapokibart in Adults with Moderate-to-Severe Atopic Dermatitis: An Open-Label Extension, Nonrandomized Clinical Trial.

Stapokibart/CM310, a humanized monoclonal antibody targeting the interleukin-4 receptor α chain, has shown promising treatment benefits in patients with moderate-to-severe atopic dermatitis in previous phase II clinical trials. We aimed to evaluate the long-term efficacy and safety of stapokibart in adults with moderate-to-severe atopic dermatitis. Enrolled patients who previously completed parent trials of stapokibart received a subcutaneous stapokibart 600-mg loading dose, then 300mg every 2weeks up to 52weeks. Efficacy outcomes included the proportions of patients with ≥50%/75%/90% improvements from baseline of parent trials in the Eczema Area and Severity Index, Investigator's Global Assessment, and weekly average of the daily Peak Pruritus Numerical Rating Scale. In total, 127 patients were enrolled, and 110 (86.6%) completed the study. At week52, the Eczema Area and Severity Index-50/75/90 response rates were 96.3%, 87.9%, and 71.0%, respectively. An Investigator's Global Assessment 0/1 with a ≥2-point reduction was achieved in 39.3% of patients at week16, increasing to 58.9% at week52. The proportions of patients with ≥3-point and ≥4-point reductions in the weekly average of daily Peak Pruritus Numerical Rating Scale scores were 80.2% and 62.2%, respectively, at week52. Improvement in patients' quality of life was sustained over a 52-week treatment period. Treatment-emergent adverse events occurred in 88.2% of patients, with an exposure-adjusted event rate of 299.2 events/100 patient-years. Coronavirus disease 2019, upper respiratory tract infection, and conjunctivitis were the most common treatment-emergent adverse events. Long-term treatment with stapokibart for 52weeks showed high efficacy and good safety profiles, supporting its use as a continuous long-term treatment option for atopic dermatitis. ClinicalTrials.gov identifier: NCT04893707 (15 May, 2021).

A child is worried about heartburn: modern views on the problem and possibilities of non-pharmacological support

Background. The relevance is associated with a significant spread of dyspeptic symptoms in children. On average, every third-fourth child with such symptoms complains of heartburn, which is a frequent reason for consulting a doctor. For the pediatric category of patients, not only the timely diagnosis and effective treatment of pathological conditions associated with heartburn are important, but also the awareness of the parents of our patients and the children themselves about the possibilities of providing ade­quate first aid, safe and effective use of effective non-medicinal means. The purpose: to study the clinical effectiveness of using the special drink ISOTA for the first aid and preliminary treatment of children with heartburn in non-erosive reflux disease, functional dyspepsia and a combination of these conditions (overlap of non-erosive gastroesophageal reflux disease and functional dyspepsia). Materials and methods. Design: a single-center, open-label, pilot clinical trial. Fifty-four children aged 7–18 years with heartburn and other dyspeptic complaints were under observation. The study included 2 stages. The diagnosis was verified by means of surveys (GERDQ and QOLRAD questionnaires) and the use of fibrogastroscopy, endoscopic pH-metry. The results were recorded in the developed individual patient card and statistically processed. Results. Results of the study presented in the corresponding section testify to the high effectiveness of using ISOTA to eliminate heartburn and reduce other dyspeptic symptoms, as well as to a reliable improvement in the psychoemotional state, general well-being and quality of life of patients. Conclusions. The obtained results make it possible to recommend a slightly carbonated hydrocarbonate-containing special drink developed in Ukraine for a long-term use in a treatment course or as needed, and prophylactically to prevent heartburn and other dyspeptic symptoms in children, taking into account the high profile of effectiveness, safety and good tolerabi­lity.