Efficacy Parameters Research Articles

A randomized, double-blind, placebo controlled study to evaluate the effect of alpha-lipoic acid on inhibition of ADP-and collagen-induced platelet aggregation ex vivo in diabetic neuropathy patients on gabapentin or pregabalin.

Diabetic peripheral neuropathy (DPN) is a chronic microvascular complication in diabetic mellitus patients due to chronic hyperglycemia, resulting in platelet hyperactivity and dyslipidemia. Alpha-lipoic acid (ALA) is a potent antioxidant which has antiplatelet activity and lipid-modulating characteristics and plays a major role in the prevention of disease progression. To evaluate the effect of ALA on inhibition of platelet aggregation and lipid profile. This was a prospective, randomized, double-blind, placebo-controlled study conducted at the Department of Clinical Pharmacology and Therapeutics at a tertiary care hospital. We recorded efficacy parameters including changes in inhibition of platelet aggregation, lipid profile, blood sugars, and glycated hemoglobin over 12 weeks of ALA (600 mg once daily orally) supplementation in DPN patients on gabapentin (300 mg twice daily [BD]) or pregabalin (75 mg BD) compared to placebo. We used Student's t-test paired and unpaired for within-group and between-group comparisons, respectively. A total of 52 study participants (males = 22, females = 30) with a mean age 55.63 ± 7.5 years were randomized to receive either ALA or placebo. Between-group analysis at 12 weeks showed that ALA significantly inhibited both collagen-induced platelet aggregation (from 32.61 ± 8.00 to 24.88 ± 5.30; P < 0.001) and adenosine diphosphate-induced platelet aggregation (from 34.00 ± 6.97 to 25.96 ± 6.45; P < 0.001) compared to placebo. Significant reduction in total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and triglycerides was found in the ALA group at 12 weeks compared to baseline. No serious adverse events were reported. ALA, an antioxidant, demonstrated a protective effect against DPN by the virtue of its inhibitory effect on platelet aggregation and lipid-modulating effects and was found to have good safety.

Fasting mimicking diet during neo-adjuvant chemotherapy in breast cancer patients: a randomized controlled trial study

ObjectivePreclinical evidences suggests that while fasting can reduce the side effects and toxicity of chemotherapy, it can make cancer cells more susceptible to chemotherapy. This study aimed to examine the effects of fasting mimicking diet (FMD) during neo-adjuvant chemotherapy in breast cancer (BC) patients.MethodsForty-four newly diagnosed human epidermal growth factor receptor 2-negative (HER2-negative) patients with BC were randomized equally into two groups (22 each), to receive either a fasting mimicking diet (FMD) or their regular diet for 3 days prior to and during neoadjuvant chemotherapy. This FMD was repeated every 3 weeks for 8 cycles. Efficacy, toxicity, hematologic, metabolic, and inflammatory parameters were measured and compared.ResultsThe occurrence of grade III vomiting and neutropenia in the control group was significantly higher than the FMD group (P = &amp;lt;0.001 and p = 0.04 respectively). Erythrocytes (p = 0.01) and neutrophils (p = 0.002) counts were significantly higher in FMD group compared to control group after cycle 8. There was a significant increase in median glucose and median insulin levels (p = 0.01 and p = 0.005, respectively) in the control group between baseline and after cycle 8. While, the median Insulin-like growth factor-1 (IGF1) (p = 0.006) and hs-CRP (p = 0.02) levels were significantly decreased in the FMD group. At the end of study (after cycle 8), the median glucose level was significantly higher in control group (p = 0.008), while the median hs-CRP level was significantly lower in FMD group (p = 0.01). The Miller and Payne pathological response 4/5 (90–100% tumor cell loss) and the radiologically complete or partial response, as measured by MRI or ultrasound before surgery occurred more frequently in FMD group compared to the controls (p = 0.01).ConclusionFasting mimicking diet was well tolerated during chemotherapy and reduced toxicity of chemotherapy and also, had beneficial effects of some metabolic parameters.Clinical Trial Registrationhttps://irct.behdasht.gov.ir/user/trial/61386/view.

Prediction of the efficacy of neoadjuvant chemoradiotherapy in patients with rectal cancer based on a texture analysis of T2-weighted magnetic resonance tumor image obtained at primary staging

BACKGROUND: Recently, significant efforts have been undertaken to find potential noninvasive biomarkers for predicting the response of locally advanced rectal cancer to neoadjuvant chemoradiotherapy. AIM: To assess the texture characteristics of locally advanced rectal cancer in primary T2-weighted imaging (T2-WI) as a potential predictor for the efficacy of standard neoadjuvant chemoradiotherapy and develop a prediction system for the efficacy of neoadjuvant chemoradiotherapy based on them. MATERIALS AND METHODS: The retrospective study enrolled 82 patients with locally advanced rectal cancer who received combination treatment with neoadjuvant chemoradiotherapy. Patient data were divided into the training (n=58) and control (n=24) sets. For texture analysis, primary high-resolution T2-WI at the level of the tumor center, oriented perpendicular to the intestinal wall, was used. The texture analysis was performed by second-order statistics based on the gray-level co-occurrence matrices using MAZDA ver. 4.6 featuring the calculation of 11 texture parameters. In the training set, based on the morphological assessment of surgical specimens, significantly different texture analysis parameters were found for two groups of patients: neoadjuvant chemoradiotherapy responders (good prognosis group) and nonresponders (poor prognosis group). Accordingly, a scoring system was created for assessing the efficacy of neoadjuvant chemoradiotherapy. The system was tested on the control set, and diagnostic efficacy parameters were determined. RESULTS: In the training set, the good and poor prognosis groups differed significantly in five texture parameters: AngScMom (p=0.021), SumofSqs (p=0.003), SumEntrp (p=0.003), Entropy (p=0.038), and SumVarnc (p=0.015), for which the cutoff points were found. These parameters were applied to create the scoring system (excluding the Entropy parameter, which had a strong direct correlation with SumEntrp and the lowest area under the curve, and SumofSqs, which had low reproducibility). The diagnostic efficiency of the scoring system for predicting the response had sensitivity, specificity, positive-predictive value, and negative- predictive value of 72%, 69%, 70%, and 71% for the training set and 80%, 64%, 62%, and 82% for the control set, respectively. The areas under the ROC curve were 0.77 and 0.72 for the training and control sets, respectively. CONCLUSIONS: Texture analysis of the primary T2-WI of tumors in patients with locally advanced rectal cancer allows for predicting the efficacy of neoadjuvant chemoradiotherapy with moderate diagnostic efficiency. The results suggest good prospects for further research in this area.

Safety and Efficacy of Calcitonin Gene-related Peptide Receptor Antagonists and Selective Serotonin Receptor Agonist in the Management of Migraine: A Systematic Review and Meta-analysis.

Recently, US Food and Drug Administration (FDA) has approved calcitonin gene-related peptide receptor antagonists (rimegepant, and ubrogepant), and selective serotonin receptor agonists (lasmiditan) in the management of migraine. However, the exact safety and efficacy profile of these drugs is unclear so far. The study's primary objective was to determine the exact safety and efficacy profile. The overall estimate was calculated in terms of risk ratios using a suitable model. The subgroup analysis was also performed to check the effect of individual drugs on the outcome, whereas sensitivity analysis was performed to check the effects of outliers on the outcome. All the analyses were performed using Rev Man 5. The drugs have shown significant improvement in efficacy parameters (pain freedom, most bothersome symptoms, phonophobia, nausea, and photophobia). The subgroup analysis results have shown significant improvement in all efficacy parameters in the rimegepant and ubrogepant groups. The effect of ubrogepant on safety parameters was found to be non-significant, indicating a better safety profile of ubrogepant than lasmiditan. The sensitivity analysis results have shown no effect of outliers on the efficacy parameters. Based on the available evidence, recently approved drugs are effective in the treatment of migraine, however, associated with few adverse drug reactions.

Efficacy and safety of RET-TKI in advanced RET-rearranged non-small cell lung cancer in China: areal-worldretrospective chart review.

Selective RET inhibitors have been approved by the Chinese government for the treatment of RET-rearranged non-small cell lung cancer. This study aimed to illustrate the efficacy and safety of selective RET inhibitors in a real-world clinical context in China. Patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring RET rearrangement and receiving RET tyrosine kinase inhibitors (RET-TKI) in the real world were enrolled in this retrospective study. Clinical data, including baseline clinicopathological information, efficacy parameters such as objective response rate (ORR) and progression-free survival (PFS), and adverse events (AEs), were collected from the electronic medical record system. The pattern of treatment failure of first-line RET-TKI was also described. Fifty-one patients were enrolled in this study. RET-TKI induced an ORR of 73.1% and a median PFS (mPFS) of 22.7months (95%CI, 11.7-33.7) in the first-line setting. The ORR and mPFS were 58.3% and 17.7months (95%CI, 9.1-26.2), 55.6% and 14.7months (95%CI, 12.6-16.8) in the second-line and later-line settings, respectively. No significant difference was observed among different application lines with respect to the ORR (P = 0.534) or PFS (P = 0.795). In the first-line setting, RET-TKI significantly prolonged PFS compared to other regimens including chemotherapy-based regimens, multikinase inhibitors and other systemic regimens without chemotherapy (P < 0.05). Poor ECOG performance status was related to shorter PFS (P = 0.018). The most common AEs of grade 3 or worse were a decreased neutrophil count (11.4%) and anemia (11.4%). No new AEs or grade 5 AEs were observed. Brain metastasis was one of the most common patterns of treatment failure. In patients with baseline brain metastasis, the intracranial ORR was 50%, and the DCR was 100%. RET-TKI had favorable efficacy and safety in real-world contexts in China and should be considered the preferred choice for first-line treatment in RET-rearranged NSCLC patients.

Immuno-physiological role of exogenous enzymes supplementation in heat stressed growing calves

Twenty Crossbred (Baladi× Brown-Swiss) male growing-calves, 6 to 8 months old, weighing an average of 115 to 125 kg were subjected for evaluating ZADO supplementary effects on blood biochemical parameters, antioxidant status, thyroid activity, and growth efficiency of calves under semi-arid conditions. The experimental units were pinned equally in two groups. The control (G1) fed the basal ration, and the 2nd, treatment group (G2) fed the basal ration + a daily supplement of 10 g ZADO (exogenous enzymes) calf− 1 day− 1 in a powder form mixed well with ration. The results showed that ZADO treatment reduced (P < 0.001) each of respiration rate (RR), rectal temperature (RT), serum malondialdehyde (MDA), urea, creatinine, and cortisol. Also, caused a marked decline in oxidized glutathione (GSSG) and alanine aminotransferase (ALT) activities. However, supplemented ZADO to growing calves diets improved antioxidant status including reduced glutathione (GSH) and superoxide dismutase (SOD) activities, total antioxidant capacity, serum total protein, albumin, and globulin, as well as IgG and IgM besides. ZADO enhanced (P < 0.01) thyroid activity, and feed efficacy parameters. Finally, supplementing growing calves with ZADO under semi-arid circumstances alleviates the heat stress effect, and leads to an improvement in calves’ growth performance.

Efficacy and safety of maintenance intravenous immunoglobulin in generalized myasthenia gravis patients with acetylcholine receptor antibodies: A multicenter, double-blind, placebo-controlled trial.

Prospective, randomized, controlled trials of intravenous immunoglobulin (IVIG) maintenance therapy in myasthenia gravis (MG) are lacking. In this trial, we evaluated the safety and efficacy of caprylate/chromatography-purified IVIG; (IGIV-C) in patients with generalized MG undergoing standard care. Sixty-two patients enrolled in this phase 2, multicenter, international, randomized trial (1:1 IGIV-C [2 g/kg loading dose; 1 g/kg every 3 weeks through week 21] or placebo). Efficacy was assessed by changes in Quantitative MG (QMG) score at week 24 versus baseline (primary endpoint) and percentage of patients with clinical improvement in QMG, MG Composite (MGC), and MG-Activities of Daily Living (MG-ADL) scores (secondary endpoints). Safety assessments reported all adverse events (AEs). The change in QMG at 24 weeks was -5.1 for IGIV-C and -3.1 for placebo (p = .187). Seventy percent of patients in the IGIV-C group had improvement in MG-ADL (≥2-point decrease) versus 40.6% in the placebo group (p = .025). Patients showing clinical improvement in QMG and MGC (≥3-point decrease) were 70.0% for IGIV-C versus 59.4% for placebo (p = .442) and 60.0% for IGIV-C versus 53.1% for placebo (p = .610). IGIV-C was well tolerated; serious AEs were similar between arms. Three of four MG exacerbations requiring hospitalizations occurred in the IGIV-C arm with one death. Several efficacy parameters showed numerical results greater than those seen in the placebo group. This was a small study and may have been underpowered to see significant differences. Additional studies may be warranted to fully determine the efficacy of IVIG maintenance therapy in MG.

Response Surface Methodology-Aided Optimization of Bioactive Compound Extraction from Apple Peels Through Pulsed Electric Field Pretreatment and Ultrasonication

Apple by-products (i.e., peels) are often thrown away, yet they are highly nutritious and provide numerous advantages as they contain a variety of nutrients such as vitamins, minerals, and antioxidants. Apple peels also comprise a high level of antioxidants, particularly polyphenols and flavonoids. This research aimed to determine the most efficacious extraction techniques and parameters to accomplish maximum bioactive compounds recovery from apple peels. Several extractions were conducted, including stirring, ultrasonication, and pulsed electric field-assisted extractions. Response surface methodology and several factors such as temperature, extraction duration, and solvent composition were considered to have a major impact on the isolation of bioactive compounds. The findings indicated that the most practical and efficient approach was to combine the pulsed electric field process with ultrasonication and stirring at 80 °C for 30 min, while 75% aqueous ethanol comprised the optimal solvent concentration, demonstrating the critical role of the solvent in optimizing extraction efficiency. The optimal conditions were obtained through response surface methodology with a statistical significance of p &lt; 0.05. The extract exhibited a total polyphenolic content (TPC) of 17.23 mg gallic acid equivalents (GAE) per g of dry weight (dw), an ascorbic acid content (AAC) of 3.99 mg/g dw, and antioxidant activity of 130.87 μmol ascorbic acid equivalents (AAE)/g dw, as determined by FRAP and 95.38 μmol AAE/g dw from the DPPH assay. The measured antioxidant activity highlighted the significant potential of apple peels as a cost-effective source of exceptionally potent extracts.

Real-world Evidence for Enfortumab Vedotin in Patients with Metastatic Urothelial Cancer: An Austrian Multicentre Study

AimEnfortumab vedotin (EV) represents a novel treatment for patients with locally advanced or metastatic urothelial carcinoma (la/mUC) refractory to platinum-based chemotherapy and PD(L)-1 containing therapies. Real-world data are crucial for informing health policy decisions and validating clinical trial findings. MethodsWe conducted a multicentre, retrospective real-world analysis comprising 128 patients with la/mUC from 16 Austrian centres treated with EV from April 2022 to April 2024, presenting the second largest real-world cohort to date. Data were analysed for efficacy and safety parameters. ResultsThe median age was 69 years, the objective response rate 31% and the disease control rate 47%, with 9% of patients exhibiting a complete remission, 23% a partial remission and 16% a stable disease. After a median follow-up of 6.2 months, the median progression-free survival (mPFS) and the median overall survival (mOS) reached 4.8 and 10.75 months, respectively. Patients with good ECOG PS 0-1, metachronous metastatic disease and absence of liver metastases had significantly better OS. No difference in efficacy was observed in patients who received a reduced dose EV after experiencing adverse events. The safety profile was acceptable, showing grade ≥3 TRAEs in 25.8% of patients. ConclusionIn our real-world population, the administration of EV was feasible and effective, with no new safety signals. Lower efficacy data compared to previous trials might be explained by the use in later therapy lines and in patients with poorer ECOG PS. Our data corroborate the efficacy and safety of EV monotherapy in later lines.

Empagliflozin use in cardiac transplant patients

Objectives: Sodium-glucose transport protein 2 inhibitor |(SGLT2) drugs are used to treat patients with type 2 diabetes. In additions to their beneficial metabolic effects in lowering the glaciated hemoglobin, body weight and blood pressure, these agents have shown favorable and protective effects on the heart and the kidneys. These cardio renal benefits are seen even in people without diabetes. There is little evidence on the safety and efficacy of SGLT2 inhibitors use in cardiac transplant recipients. We wanted to study the cardiac transplant recipients who used Empagliflozin for the treatment of diabetes to evaluate its safety and efficacy in this niche sub group of patients. Method: We retrospectively identified 20 patients on the cardiac transplant recipient register taking Empagliflozin (Jardiance) or Empagliflozin combined with Metformin (Synjardy). We studied the safety and efficacy parameters. Results: Our results show improvement in HBA1c, body weight and stability in serum creatinine. There was no increased risk of genitourinary infection, hypoglycemia or diabetic ketoacidosis. Conclusion: While we need larger studies in cardiac transplant patients taking Empagliflozin, our small study provides assurance that Empagliflozin is safe to use in cardiac transplant recipients.

Radiomics-based multimodality prediction of left atrial appendage thrombus using coronary computed tomography angiography

Abstract Background Timely detection of thrombus in the left atrial appendage (LAA) may help guide decision-making. However, existing models have challenges in extracting comprehensive image information. It has been shown that radiomics-based prediction models can be used for accurate identification. This study investigates potential radiomic markers and constructs a highly efficient multimodality prediction model for LAA thrombus in patients undergoing coronary computed tomography angiography (CCTA). Methods We retrospectively enrolled patients with nonvalvular atrial fibrillation (NVAF) who underwent CCTA and transesophageal echocardiography (TEE) from May 2015 to May 2020. These patients were classified into thrombus or non-thrombus groups based on TEE findings. The data were balanced by resampling and assigned to training or test sets. Radiomics was conducted on the extracted features, and a random forest algorithm was employed for feature selection and importance ranking. We constructed different multimodality thrombus prediction models and compared their performance using the area under the receiver operating characteristic curve (AUC) and other efficacy parameters. Results Among 670 patients (60.17±10.98 years, 70.1% male), 5.2% (n=35) had LAA thrombi. A total of 1232 radiomics features were extracted, with 25 features selected using a random forest for modeling. Two radiomics features (Ibp_3D_m1_firstorder Skewness and original_shape_Flatness) ranked the highest. The radiomics-based multimodality prediction model achieved an AUC of 0.964 (95% confidence interval [CI]: 0.947-0.982), an accuracy of 0.926 (95% CI: 0.925-0.926), and an F1 score of 0.924, outperforming other traditional prediction models. Decision curve analysis also indicated that this model provided the best net clinical benefit. Conclusions Radiomics facilitates a comprehensive exploration of predictors associated with LAA thrombi. A radiomics-based multimodality prediction model can significantly enhance the efficiency of non-invasively detecting thrombi.Receiver operating characteristic curveDecision curve analysis

Evaluating efficacy and safety of ocrelizumab biosimilar (Xacrel) compared to the originator (Ocrevus) in relapsing multiple sclerosis: a phase III, randomized, equivalency, clinical trial

Multiple sclerosis is an inflammatory demyelinating disease and represents a global health concern. Ocrelizumab, a humanized IgG monoclonal antibody, selectively targets CD20 on B cells and CD20-expressing T cells. This study aimed to compare the efficacy and safety of the biosimilar ocrelizumab candidate (Xacrel) to the originator product (Ocrevus) in Relapsing Multiple Sclerosis (RMS) patients. In this randomized trial, patients received either Xacrel or Ocrevus for 96 weeks. The primary endpoint was the equivalency of the medications in reducing the annualized relapse rate (ARR) at week 48. The secondary endpoints included time to the onset of disability progression confirmed at 12 and 24 weeks, the proportion of relapse-free patients, magnetic resonance imaging (MRI) evaluations, safety assessments, and immunogenicity over 96 weeks. A total of 170 patients were randomized (1:1 ratio). In the per protocol analysis, the upper and lower limits of 95% two-sided confidence intervals of difference between treatments in the 48-week ARR rate were in the predefined margin of − 0.2 to 0.2 (− 0.002; 95% CI − 0.080 to 0.075). The two products were also comparable in terms of other efficacy parameters, safety, and immunogenicity. The results confirmed that Xacrel is equivalent to Ocrevus in terms of 48-week ARR in RMS patients, with no considerable difference in other efficacy parameters and the safety profile during the 96 weeks. The trial was registered in Iranian registry of clinical trials (IRCT) on 10/06/2019 with the registration number of IRCT20150303021315N13 and in Clinicaltrials.gov on 19/07/2021 with the registration code of NCT04966338.

Efficacy of Topical Hydroxypinacolone Retinoate-Peptide Product Versus Fractional CO2 Laser in Facial Aging.

Many people are interested in addressing visible signs of aging with non-invasive cosmetic treatments. Development of effective topical products will provide options to delay or support cosmetic procedures. This study assessed and compared the efficacy and tolerance of a topical product used over the course of 16 weeks to a single ablative laser treatment on women with moderate global photodamage on the face. Subjects in Cell 1 (Laser Cell) were treated over the entire face with a fractional CO2 laser system. Subjects in Cell 2 (Topical Serum Cell) were treated with a topical serum containing hydroxypinacolone retinoate and peptides over the entire face, twice per day for 16 weeks. The study was composed of 71 women, with 29 in the Laser Cell (mean age 56.2) and 42 in the Topical Serum Cell (mean age 55.0), between 40 and 65 years old. Expert grading was used to determine efficacy parameters. Participants in the Topical Serum Cell achieved more significant improvement (p < 0.05) in Marionette lines, fine lines (global face), wrinkles (global face), wrinkles (crow's feet), nasolabial folds, texture, smoothness (tactile), global hyperpigmentation, lift, and photodamage compared to participants in the Laser Cell. Participants in the Topical Serum Cell achieved parity in the look of fine lines (crow's feet), forehead lines, glabella, firmness/bounce (tactile), skin tone evenness, radiance. While no statistically significant differences in tolerability were observed, treatment with the topical cosmetic product achieved parity or statistically better improvement in parameters compared to laser treatment at 16 weeks.

Updated overall survival and ctDNA analysis in patients with EGFR T790M-positive advanced non-small cell lung cancer treated with lazertinib in the phase 1/2 LASER201 study.

Lazertinib is a potent, irreversible, third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with significant efficacy in patients with EGFR T790M-mutated non-small cell lung cancer (NSCLC). This is the final overall survival (OS) report from the phase 1/2 LASER201 study in patients with advanced NSCLC with disease progression on or after prior EGFR TKI therapy. Eligible patients were aged ≥ 20years, with advanced EGFR-mutated NSCLC and previous therapy with EGFR TKI. Patients in this integrated analysis received oral lazertinib 240mg/day. Endpoints included efficacy and safety; exploratory analyses included associations between circulating EGFR-mutant tumor DNA (ctDNA) and efficacy parameters. This integrated analysis included 78 patients in Korea who received second- or later-line lazertinib. The median OS was 38.9months; estimated survival rates at 12, 24, and 36months were 89.5%, 73.9%, and 52.8%, respectively. The cumulative 12-month incidence of central nervous system progression was 9.4%. EGFR-mutant ctDNA was detected in 46 patients (62.2%) at baseline. The presence of ctDNA at baseline significantly predicted progression-free survival (PFS), disease control rate (DCR), and OS. PFS, response rate, and DCR were significantly associated with EGFR-mutant ctDNA clearance at cycle 3; PFS and OS were significantly associated with ctDNA clearance at cycle 5. The safety profile of lazertinib 240mg/day was consistent with previous findings. Lazertinib is a promising treatment option for patients with EGFR T790M-positive NSCLC following disease progression on prior EGFR-directed TKIs. Patients in LASER201 experienced prolonged OS, regardless of their EGFR mutation, brain metastases, or prior brain radiation status. Clearance of plasma EGFR mutations after lazertinib was associated with patient outcomes. ClinicalTrials.gov identifier NCT03046992.

Long-Term (12-Month) Safety and Tolerability of STS101 (Dihydroergotamine Nasal Powder) in the Acute Treatment of Migraine: Data from the Phase 3 Open-Label ASCEND Study.

STS101 is an investigational drug-device combination comprising 5.2 mg dihydroergotamine (DHE) powder (6.0 mg DHE mesylate) in a single-use nasal delivery device for the acute treatment of migraine. The primary objective of the ASCEND trial was to assess long-term safety and tolerability of STS101 in the acute treatment of migraine attacks across 12-18 months, with secondary objectives describing efficacy. ASCEND was an open-label study of STS101 in adults aged 18-65 years with a ≥ 1 year history of migraine with or without aura, with onset before the age of 50 years and 4-12 migraine attacks/month and < 15 headache days/month in each of the 3 months prior to screening. Exclusion criteria included diagnosis of non-migraine headache, history of cerebrovascular disease, and ≥ 2 cardiovascular risk factors. After establishing eligibility, participants could self-administer STS101 5.2 mg as needed for up to 2 doses within 24 h to treat a single migraine attack and up to 12 doses/month. Safety and tolerability evaluations included physical and nasal examinations, vital signs, laboratory tests, and treatment-emergent adverse event (TEAE) assessments. Participants used an electronic diary to record exploratory efficacy parameters, including intensity of headache pain and associated migraine symptoms (photophobia, phonophobia, and nausea). Participant impression questions were asked at months 3, 6, and 12. Of the 6610 migraine attacks treated with a total of 8234 STS101 doses in 344 participants, 945/6610 (14.3%) were associated with a TEAE. Events were predominantly mild or moderate in nature and rarely led to premature study discontinuation (15/344 [4.4%] participants). Treatment was associated with rapid onset of freedom from pain (36.6%, 67.1%, and 85.5% of treated attacks 2, 4, and 24 h post-dose, respectively), freedom from most bothersome symptoms (54.3%, 79.6%, and 91.3%), and headache relief (66.5%, 89.1%, and 94.3%). Most participants rated treatment results as good or very good and ease of use as easy or very easy at all time points (months 3, 6, and 12) and indicated they were likely or very likely to use STS101 again. The repeated long-term, as-needed use of STS101 was well tolerated, demonstrating a favorable safety profile in the acute treatment of migraine attacks in appropriately indicated adults. Exploratory efficacy evaluations indicated beneficial effects, which warrant further evaluation. ClinicalTrials.gov identification NCT04406649.

8120 Effective Management of Neonatal Hypercalcemia in Congenital Mesoblastic Nephroma: A Case Report on the Use of Calcitonin

Abstract Disclosure: C.S. Galvez: None. K. Rifai: None. C. Moorthy: None. S. Chheda: None. M. Zerah: None. Introduction: Pediatric patients with hypercalcemia of malignancy are typically treated with hyperhydration, loop diuretics and bisphosphonates. Calcitonin, a peptide functionally antagonizes the effects of PTH. Calcitonin has limited pharmacokinetic data in neonates, especially those with Congenital Mesoblastic Nephroma (CMN), making treatment challenging with unclear safety and efficacy parameters. We present the fourth published case describing the use of calcitonin for likely PTH-rP-mediated severe hypercalcemia in a neonate with CMN. Clinical Case: A 15-day-old late preterm male, presented with lethargy, poor feeds, severe failure to thrive and a large abdominal mass. The mother is a G4P4, with good prenatal care. On admission, the patient was hypertensive (138/84 mmHg) and appeared dehydrated. Physical examination revealed a firm mass in the right abdomen crossing the midline. Serum calcium levels were 13.5 mg/dL (normal 9.0-10.9 mg/dL), with an ionized calcium 1.71 mmol/L (normal 1.15 and 1.30 mmol/L). Abdominal ultrasound showed a large, 9.1 x 8 cm dominant solid right renal mass, most likely CMN, with left-sided medullary nephrocalcinosis. Cardiac Echo and EKG were within normal limits. The patient received hydration, nicardipine (titrated to decrease blood pressure by 10-15 mmHg per day) and furosemide at 1 mg/kg/day IV q6h. Due to the persistence of hypercalcemia after 24 hours of treatment (14.7 mg/dL serum calcium with ionize of 1.81 mmol/L), the patient received one dose of calcitonin (4 units/kg subcutaneously), resulting in a decrease in serum calcium to 11.5 mg/dL in 4 hours. The patient underwent a successful radical right uretero-nephrectomy, with post-surgery improvement of neurological, cardiovascular and electrolyte status. Unfortunately, PTH-rP sample was insufficient. Pathology reported CMN of the cellular type. CMN is a rare tumor with low malignant potential, representing approximately 3% of all pediatric renal tumors. It is the most common renal neoplasm diagnosed in the first 6 months of life. The most common symptom is an abdominal mass (76%), with hypertension (19%). Hypercalcemia was reported in only 4% which can be secondary to paraneoplastic secretion of PTH or PTH-rP. Conclusion: This case represents the fourth instance of calcitonin use in a neonate with CMN to manage persistent hypercalcemia. Subcutaneous administration of calcitonin at 4 units/kg proved effective with a short onset of action (within 2 hours) and duration of 6 to 8 hours, making it a viable alternative to bisphosphonates (action around 48 hours and duration of 7 to 14 days). Calcitonin's advantages include less significant side effects and a faster resolution of complications like "Hungry bone Syndrome." The flexibility of repeated dosing every 6 hours, with the option to increase the dose, if necessary, adds to its clinical utility. Presentation: 6/3/2024

Prophylaxis of respiratory syncytial virus infection: current status and prospects for vaccine development

INTRODUCTION. Respiratory syncytial virus (RSV) is one of the most widespread pathogens that typically cause acute upper and lower respiratory tract infections in children and adults. Monoclonal antibody products have long been used for passive immunoprophylaxis in premature infants with bronchopulmonary dysplasia. However, vaccines have recently been licensed for the prophylactic immunisation of older adults with various risk factors for severe RSV infection (primarily, chronic cardiovascular and respiratory diseases and diabetes mellitus).AIM. This study aimed to review the current status of the development of vaccines for active immunisation against RSV infection, including the epidemiological rationale for their development, clinical trial results for licensed vaccines, recommendations for vaccination, and promising pipeline vaccines for RSV prevention.DISCUSSION. Initially hindered by the unique immunopathogenesis of RSV infection and the genetic hypervariability of RSV for a long time, attempts to develop an RSV vaccine succeeded when international researchers managed to identify a conservative neutralising antibody target capable of inducing specific immunity against RSV. This target, the RSV capsid protein stabilised in its prefusion (pre-F) conformation, can mediate viral entry into the cell following a conformational change. Several subunit vaccines based on recombinant pre-F proteins have successfully passed clinical trials and have been approved for the immunisation of older adults. In addition, one of these vaccines has been recommended for use during pregnancy to prevent RSV infection in newborns and infants. Currently, programmes are being implemented to develop novel RSV vaccines based on messenger RNA (mRNA) and non-replicating attenuated influenza vectors. This article examines and summarises the efficacy and safety parameters of two RSV vaccines approved in multiple countries around the world. Both vaccines have satisfactory safety profiles and comparable prophylactic efficacy parameters.CONCLUSIONS. Prelicensure clinical trials of novel RSV vaccines, including those being developed in the Russian Federation, should include prophylactic efficacy assessments in target patient populations. For vaccines approved by leading international regulators, clinical trials required for approval in the Russian Federation will be limited to bridging studies confirming the immunogenicity and safety of the vaccines.

A Prospective Randomized Trial Comparing Quality of Life in Adult Female Acne Treated with Azelaic Acid 15% Gel versus Oral Spironolactone.

In several countries, recent research has shown an increase in the prevalence of adult female acne (AFA), defined as the acne that appears in women aged over 25. This disease brings some particularities and challenges, such as a greater impact on quality of life (QoL) and chronicity. A negative impact on QoL has been observed, as well as anxiety, depression, anger, low self-esteem, and feelings of embarrassment and frustration. To quantify AFA's impact on QoL and the influence of two dermatological treatments. A prospective study including 40 women, aging from 25 to 44 years old, with mild-to-moderate acne was conducted. Participants underwent clinical, laboratory, and photographic evaluations. They were randomized into two treatment groups: group 1 - azelaic acid (AZA) 15% gel twice daily; group 2 - spironolactone (SPIRO) 100 mg/day and treated for 6 months. At baseline and at the end of treatments, a specific QoL questionnaire for acne, already translated and validated for Brazilian Portuguese (Acne-QoL-BR), was applied. It contains 19 questions allotted in four domains. Each item within a domain is scored from 0 to 6. The total score ranges from 0 to 114 and domains are distributed as follows: 0-30 (self-perception), 0-30 (role-emotional), 0-24 (role-social), 0-30 (acne-symptoms). Higher scores reflect better QoL. The mean age was 32.7 (SD: 5.42); 85% presented persistent acne. After treatment regardless of group, there was a significant improvement in total score and all domains' scores of acne QoL-BR (p < 0.001), with no difference between groups, despite one treatment being topical and the other systemic (p=0.918). Acne-QoL-BR is a useful tool for quantifying the impact of acne and should be used as an efficacy parameter in clinical trials.

The intervention mechanism of Tanshinone IIA in alleviating neuronal injury induced by HMGB1 or TNF-α-mediated microglial activation

Tanshinone IIA (Tan IIA), a neuroprotective natural compound extracted from Salvia miltiorrhiza, is used in stroke treatment. However, elucidating Tan IIA's neuroprotective mechanisms remains challenging due to limitations in assessing drug efficacy and biochemical parameters in clinical studies. This study investigated Tan IIA's impact on neuroinflammatory responses and its neuroprotective mechanisms using HMGB1- or TNF-α-stimulated BV2 microglia in a co-culture system with primary neuron cells. The results indicated that Tan IIA significantly reduced microglial activation induced by TNF-α or HMGB1. Concurrently, Tan IIA disrupted the interactions between HMGB1 and toll-like receptor 4 (TLR4), and between TNF-α and TNF receptor 1 (TNFR1), modulating the HMGB1/TLR4/nuclear factor-kappa B (NF-κB) and TNF-α/TNFR1/NF-κB signaling pathways and related protein expressions. Moreover, co-culture experiments showed that neuronal apoptosis induced by microglial activation was reversed by Tan IIA. In conclusion, Tan IIA provides neuroprotection by modulating signaling pathways in microglia, thus preventing neuronal apoptosis. This study offers new insights into therapeutic targets for ischemic stroke.

Efficacy and Growth Performance between Two Different Ionophore Coccidiostats (Narasin and Salinomycin) in Broiler Chickens after Challenge with Eimeria spp.

The objective of this study was primarily to assess the different performance impacts of two ionophore coccidiostats (narasin and salinomycin) used to manage coccidiosis. While both products may be efficacious in controlling disease challenges, previous literature has suggested that some ionophores are less well tolerated by the broiler chickens. In this study, we were particularly interested to know how the use of different coccidiostat programs translates into broiler health and performance, as measured by zootechnical parameters such as the feed conversion ratio, average daily gain, and final body weight. A total of 352 male Ross 308 one-day-old broilers were randomly divided into two treatment groups (T1 and T2). Treatment 1 included a basal diet (BD) + nicarbazin/narasin (Maxiban®, Elanco) at 100 ppm 0-24 days, narasin at 70 ppm 25-42 days, and (2) Treatment 2 included basal diet + nicarbazin/narasin at 100 ppm 0-24 days, salinomycin (Sacox®, Huvepharma) at 70 ppm 25-42 days. Efficacy and performance parameters, slaughter analysis, dry matter (DM) in litter, and intestinal integrity (I2) were measured for the broilers from both treatment groups. The findings demonstrated more favorable results for broilers reared in the group diet fed with narasin (in the finisher phase), including higher daily body weight gain, higher final body weight, lower feed conversion ratio value (improved feed efficiency), and higher European Production Efficiency Factor value, compared with the salinomycin-supplemented group.