Double-blind Study Research Articles

Diagnostic Utility of Canine C-Reactive Protein, Haptoglobin, and 25-Hydroxyvitamin-D in Dogs with Nasal Cavity Disease

In this prospective blinded study, canine C-reactive protein (c-CRP), haptoglobin (HPT), and 25-hydroxyvitamin-D (25(OH)D) were investigated for their diagnostic value in 55 dogs with nasal cavity disease (ND). After comprehensive diagnostics including a culture-dependent microbiological examination (ME) of nasal swabs, 17 dogs were excluded due to additionally detected systemic diseases or steroid pre-treatment. Included were 25 dogs with malignant ND (13 carcinomas and 12 sarcomas) and 30 dogs with benign ND (7 benign tumors, 13 idiopathic rhinitis (IR), and 10 others), as well as 10 controls. In none of the 72 dogs with ND was primary bacterial rhinitis diagnosed. Although within the reference interval, compared to the controls, c-CRP was significantly higher in dogs with ND in general and in every subgroup except for benign tumors. Serum HPT concentrations were not different among groups. Compared to the controls, 25(OH)D concentrations were significantly lower (p = 0.041) in malignant ND and sarcomas (p = 0.025). Despite pre-treatment with antibiotics (40/54; 74.1%), in 23/51 (45%) dogs, the ME was positive. Cultivated bacteria did not differ significantly between nasal diseases. The serum markers were not significantly different regarding the positivity of ME. In conclusion, the investigated serum markers were not clinically useful for the reliable detection of canine ND, as was the ME. Because of the low number of dogs with IR and positive or negative ME, further studies regarding c-CRP are needed in a larger group of IR dogs without concomitant diseases to reliably evaluate its utility in IR dogs with suspected secondary bacterial nasal infection.

Dexmedetomidine-propofol versus ketamine-propofol for sedation of cancer patients undergoing computerized tomography guided bone biopsy: a randomized double-blind trial

Background & Objective: Patients suffering from malignancy, often need to undergo computed tomography (CT) for evaluation or for CT-guided bone biopsy. They are shifted to the radio-diagnostic suite and require sedation and analgesia during this procedure. We compared the efficacy and safety of combining dexmedetomidine (DEX) or ketamine with propofol for better sedation among these patients undergoing CT-guided bone biopsy. Methodology: This randomized, double-blind study was done on 60 adult cancer patients undergoing CT-guided bone biopsy. Patients were randomized into two equal groups. Group D received DEX 1 µg/kg (over 10 min) + propofol 2.5 mg/kg intravenous (IV). It was followed by DEX 0.5 µg/kg/h + propofol 2.5 mg/kg/h infusion. Group K received ketamine 1 mg/kg + propofol 2.5 mg/kg IV, followed by ketamine 0.25 mg/kg/h + propofol 2.5 mg/kg/h infusion. Results: The total intra-procedure propofol consumption was significantly decreased in Group D than in Group K (P < 0.05). The visual analog scale score at 15 min and 30 min post-procedure, number of patients requiring morphine and paracetamol within one hour of procedure and the recovery times were significantly decreased in Group D than in Group K (P < 0.05). Mean arterial pressure (MAP) and heart rate (HR) measurements at 10 min, 20 min, end of the procedure, and 15 min, 30 min post-procedure was significantly decreased in Group D than in Group K (P < 0.05). Adverse events, e.g., postoperative nausea and vomiting, hypotension, and bradycardia, were comparable. Conclusion: DEX-propofol combination had superior sedation efficacy as noted through lower pain scores, intraprocedural propofol or postprocedural morphine and paracetamol consumption, and the shorter recovery time during CT-guided bone biopsy compared to ketamine-propofol combination. However, ketamine-propofol combination exhibited superior hemodynamic stability, as shown by more consistent HR and MAP. Keywords: Dexmedetomidine; Ketamine; Propofol; Computed tomography; Bone biopsy; Morphine Citation: Abdelgalil AS, Mohammed AM, Abdelrahman AS, Zayed NOA. Dexmedetomidine-propofol versus ketamine-propofol for sedation of cancer patients undergoing computerized tomography guided bone biopsy: a randomized double-blind trial. Anaesth. pain intensive care 2024;28(5):809−815; DOI: 10.35975/apic.v28i5.2554 Received: Jun 17, 2024; Reviewed: Jul 31, 2024; Accepted: Aug 19, 2024

Effect of nutrient support on structural and functional parameters of facial skin

Aims: to study the effect of oral administration of biologically active supplement "VITABEAUTY® Hyaluronic Acid + Resveratrol" on structural and functional parameters of facial skin. Materials and methods: a simple blind placebo-controlled cross-over study was conducted in which 40 female patients aged 30 to 45 years with signs of dryness, decreased hydration and elasticity of facial skin, the first signs of aging and wrinkles took part. The observation was carried out for 10 weeks. The dietary supplement and placebo were taken according to the following scheme: during the first 4 weeks of the study patients received placebo, then the subjects took "VITABEAUTY® Hyaluronic Acid + Resveratrol" for the next 6 weeks. Results: the study participants were not aware of whether they were taking placebo or the dietary supplement "VITABEAUTY® Hyaluronic Acid + Resveratrol" at the moment. Objective assessment of skin condition was carried out 4 and 10 weeks after the beginning of the study in strictly fixed points of anatomical formations of the face: medial part of the forehead and central zone of the right cheek. The software and hardware complex MultiskinTestCenterMC 900 (Courage + Khazakaelectronic GmbH, Germany) was used to evaluate the study of skin functional properties. Moisture content was investigated by the corneometry method based on the measurement of the electrical capacitance of dielectric medium using the "Corneometer®" sensor. Conclusions: sebumetry was assessed by photometric method using a transparent film that fixes the amount of sebum on the epidermis surface using a "Sebumeter®" sensor. The state of epidermis barrier function was investigated by measuring the transepidermal water loss (TEWA) using the sensor "TewametereTM300". The elastic properties of the skin were studied by assessing the degree of skin retraction and straightening under negative pressure of 400 mbar using a "Cutometer®" sensor. Topographic features of the skin were studied using the method of video dermascopy. Also during the study, patients subjectively evaluated the effectiveness of VITABEAUTY® Hyaluronic Acid + Resveratrol supplementation.

Evaluation of the effectiveness and safety of Korean red ginseng extract as immune-enhancer in Vietnamese adults: A randomized placebo-controlled trial

Purpose: To investigate the safety and immune-enhancing effect of Korean red ginseng (KRG) extract in Vietnamese adults. Methods: Participants in this randomized, placebo-controlled double-blinded study were administered either 960 mg of KRG extract (n = 51) or placebo capsules (n = 50) for 12 weeks at Hanoi Medical University, Vietnam. The KRG extract was standardized to contain 5.27 mg of 3 ginsenosides (Rg1, Rb1, and Rg3) per gram. Blood samples for assessment of treatment effectiveness were collected from the subjects on days 21 and 84. Immune cytokines were quantified using enzyme-linked immunosorbent assay (ELISA). Blood samples for safety assessment, hematological and biochemical variables, and urinalysis were performed at the beginning and end of the intervention (days 21 and 84, respectively). Results: The KRG group showed a significant increase in lymph T cell % at the end of the 12-week intervention (p < 0.001). There were significant decreases in numbers of white blood cells (WBC) and natural killer (NK) cells in both groups. However, there were no significant differences in populations of WBC and NK cells between the 2 groups. Serum concentrations of cytokines, i.e., TNF-α, β, γ; IFN- α, γ; IL-1β and 4β were decreased in the KRG group when compared to baseline values. There were no probable or definite adverse events (AEs) related to KRG. A total of 9 participants (4 in KRG group and 5 in placebo group) tested positive for COVID-19 during the trial. Conclusion: The KRG extract-induced increase in population of T-cells and reductions in cytokine levels following a 12-week exposure may be beneficial for COVID-19 patients.

Deep Neuromuscular Block with Low Pressure Pneumoperitoneum in Laparoscopic Abdominal Surgeries: A Randomized Controlled Trial

Background: Postoperative pain management remains a challenge in laparoscopic abdominal surgeries. Objectives: The purpose of this research was to determine the effects of deep neuromuscular blockade (NMB) in conjunction with low-pressure pneumoperitoneum )PP) on postoperative pain, surgical parameters, and recovery outcomes. Methods: This randomized controlled double-blind study included 44 participants undergoing laparoscopic abdominal surgery. Patients were randomized equally into two groups (22 each): Group D received deep NMB, while group M received moderate NMB using cis-atracurium, through the utilization of computer-generated random numbers enclosed within sealed, opaque envelopes, following a parallel approach. Regarding deep NMB, following an initial dose of 0.15 mg/kg, a continuous infusion of 0.06 - 0.12 mg/kg/hr was administered to maintain a post-tetanic count between 1 and 2, with low PP pressure of 10 - 12 mmHg. Conversely, for moderate NMB, after the same initial dose of 0.15 mg/kg, the continuous infusion commenced upon the train-of-four count returning to 2, with the rate adjusted to sustain a count between 1 and 3, and standard PP pressure of 15 mmHg. The primary outcome was postoperative pain intensity as measured by Numerical Rating Scale (NRS) scores in the post-anesthesia care unit (PACU). The secondary outcomes included postoperative pain intensity measured by NRS scores from 2 hours to 48 hours post-surgery, time to first analgesic administration, cumulative opioid consumption within the initial 48-hour postoperative period, and patient-reported satisfaction with postoperative pain management. Statistical analysis using SPSS v26 included tests for normality (Shapiro-Wilks), with parametric data analyzed by t-test, non-parametric data by Mann-Whitney, and qualitative data by chi-square/Fisher's test. Results: Group D experienced a considerably longer time until the first analgesic rescue compared to group M (9.82 ± 1.5 hours vs. 7.23 ± 1.19 hours, P < 0.001). Morphine consumption in the first 24 hours was lower in Group D (10.77 ± 1.51 mg vs. 13.09 ± 1.74 mg, P < 0.001). At 6, 8, and 12 hours postoperatively, group D exhibited significantly lower pain scores (P < 0.05). Surgical duration, surgical field quality, complication rates, and patient satisfaction were comparable between groups. Conclusions: Deep NMB combined with low-pressure PP provided superior postoperative analgesia without compromising surgical field quality or increasing complications in laparoscopic abdominal surgeries.

Safety and efficacy of up to 60h of iv istaroxime in pre-cardiogenic shock patients: Design of the SEISMiC trial.

Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre-CS patients. The SEISMiC study is a multinational, multicentre, randomized, double-blind, placebo-controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre-CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70-100mmHg for at least 2h] and clinically confirmed congestion, NT-proBNP ≥1400pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies. The study results will contribute to our understanding of the role of istaroxime in pre-CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.

A Phase II/III multicenter randomized single blind non-inferiority immunogenicity and safety study of TeddyVac™ vaccine of Human Biologicals Institute in healthy subjects of 10 years to 60 years of age

Background WHO and other health agencies recommend that tetanus toxoid (TT) should be replaced by tetanus-diphtheria (Td) vaccine taking into consideration the low coverage and waning immunity, especially for diphtheria. In this randomised, multicentre, non-inferiority study, the immunogenicity and safety of TeddyVac™ vaccine of Human Biologicals Institute were compared with an existing brand. Methods The study involved 444 eligible subjects in two age groups at four centres across India. Group A included subjects of 18–60 years and Group B subjects of 10–18 years of age. All subjects received single dose of either TeddyVac™ or the comparator vaccine as per randomisation. Blood samples for antibody titre estimation were collected before vaccination and 4–6 weeks after vaccination. Immunogenicity was assessed by estimating seroconversion rate, seroprotection rate, and geometric mean titres of antibodies. Safety was evaluated by collection and analysis of data on solicited and unsolicited adverse events. Results Overall, 441 subjects completed the study. Both the vaccine arms showed comparable seroconversion after a single dose for both the components. Both arms showed increase in seroprotection and geometric mean titres after a single dose of vaccination for both vaccine components, being significantly better for the diphtheria component in the test vaccine arm. Only few minor local and systemic adverse events were observed in both the vaccine arms. No serious adverse event was reported. Conclusion The study results indicate that the TeddyVac™ vaccine is immunogenic, safe and non-inferior to the comparator Vaccine when administered to healthy subjects of 10 to 60 years of age. CTRI Registration number CTRI/2021/07/035112

Utilization of NIRS Monitor to Compare the Regional Cerebral Oxygen Saturation Between Dexmedetomidine and Propofol Sedation in Mechanically Ventilated Critically ill Patients with Sepsis- A Prospective Randomized Control Trial.

Delirium frequently occurs in the acute phase of sepsis and is associated with increased ICU and hospital length of stay, duration of mechanical ventilation, and higher mortality rates. We utilized the Near-Infrared Spectroscopy monitor to measure and compare the regional cerebral oxygen saturation in mechanically ventilated patients of sepsis receiving either dexmedetomidine or propofol sedation and assessed the association between delirium and regional cerebral oxygen saturation. A single center prospective randomized control trial conducted over a period of two years, 54 patients were included, equally divided between propofol and dexmedetomidine groups. Patients received a blinded study drug, propofol (10 mg/mL) or dexmedetomidine (5 mcg/mL) via infusion pump according to randomization. Infusion rates were adjusted every 10 min based on weight-based titration tables, aiming for target sedation (RASS -2 to 0). Management components included pain monitoring using the CPOT score and delirium assessment using CAM-ICU score. Dexmedetomidine group showed higher mean regional cerebral oxygen saturation as compared to propofol group (P = .036). No significant differences were found in mechanical ventilation or ICU stay durations, delirium-free days, or sedation cessation reasons. Delirium occurred in 36 patients, with lower mean regional cerebral oxygen saturation as compared to non-delirious patients. The dexmedetomidine group had higher regional cerebral oxygen saturation compared to the propofol group. Delirious patients showed lower cerebral oxygen saturation than non-delirious patients, suggesting a link between sedation type, cerebral oxygenation, and delirium.CTRI registration: REF/2021/11/048655 N.

7038 Continuous Subcutaneous Hydrocortisone Infusion Is Practical And Effective In Select Patients With Adrenal Insufficiency

Abstract Disclosure: J.E. Lee: None. O. Hamidi: None. S. Mirfakhraee: None. Continuous subcutaneous hydrocortisone infusion (CSHI) via insulin pump is an alternative therapy for treating patients with adrenal insufficiency (AI) and allows for adjustable hydrocortisone delivery to provide more physiologic glucocorticoid replacement. Retrospective case series of 9 patients on CSHI showed a reduction in total daily dose of glucocorticoid by 34% and a decrease in hospitalization admissions due to adrenal crisis by 50%. In a double-blind placebo-controlled study, CSHI in patients with primary AI did not demonstrate benefit in subjective health status metrics compared to oral hydrocortisone; however, patients had good baseline subjective health scores. Due to a scarcity of data, CSHI is likely underutilized in patients who may benefit from this individualized therapy. Our research objectives were to analyze the change in total daily glucocorticoid dose, number of adrenal crises events and hospitalization days, glucocorticoid-related comorbidities, and quality of life of patients transitioned to CSHI. We performed a single-center, retrospective longitudinal follow-up study in 23 consecutive patients (87% women, median age 40 years at time of CSHI initiation) treated with CSHI between 2015 and 2023. Types of adrenal insufficiency were 48% secondary AI, 35% glucocorticoid induced AI, and 17% primary AI. CSHI delivery settings were generated by a formula that we derived using each patient’s daily oral glucocorticoid dose and preferred waking time. Median time from AI diagnosis to CSHI implementation was 41 months, and median duration of CSHI was 25 months. Total daily dose of glucocorticoid (in hydrocortisone equivalent) before CSHI vs during CSHI decreased from 30.0mg (15.0mg to 80.0mg) to 26.6mg (14.4mg to 200.5mg) (p= 0.45). Median number of adrenal crisis events decreased from 1 (0 to 13) to 0 (0 to 38) (p=0.25), and hospitalization days due to adrenal crisis decreased from 2 (0 to 46) to 0 (0 to 58) (p=0.53). No significant differences were noted for change in weight, blood pressure, diabetes, cardiovascular and cerebrovascular events, total cholesterol, LDL, and triglyceride levels. Median HDL decreased from 59 to 51 (p=0.01). In terms of subjective health status, 10 patients completed SF-36 survey while on CSHI. Significant impairments were noted in physical health, vitality, and general health with median score less than 40. At the conclusion of the study, 20 patients (87%) preferred CSHI therapy. Only 3 patients stopped CSHI for reasons of inconvenience, skin irritation at pump site, and better symptom control on oral therapy. No significant CSHI-related safety concerns were noted. In conclusion, CSHI is a safe and effective way to deliver individualized therapy to patients with difficult to control AI. CSHI led to reduction in glucocorticoid exposure and fewer adrenal crisis events and hospitalization days due to adrenal crisis. Presentation: 6/1/2024

8000 Intestinimonas Butyriciproducens As A New Preventive Therapy For Type 2 Diabetes: a Proof Of Concept Randomized Controlled Trial

Abstract Disclosure: V. Antoniotti: None. M. Caputo: None. E. Mollero: None. A. Antonioli: None. S. Tini: None. M. Manfredi: None. S. Gul: None. N. Bui: None. J. Seegers: None. W. De Vos: None. G. Aimaretti: None. F. Prodam: None. Background. The incidence of type 2 Diabetes Mellitus (T2D) is increasing worldwide. Prevention is possible by changing lifestyle but it’s not effective alone in real life, due to poor compliance over time. New strategies are necessary, mostly for high-risk individuals. Therapeutic microbiology is a further proposed target, and butyrate-producing bacteria can improve metabolic parameters in obese patients. Our study aims to evaluate the effect of Intestinimonas butyriciproducens as a preventive therapy for T2D in prediabetes thanks to its effects in decreasing Advanced Glycation End Products (AGEs), converting sugars and proteins in butyrate, and increasing insulin sensitivity.Methods. The trial is a double-blind, randomized, placebo-controlled (phase 1) and open-label pilot study with two different doses (phase 2) of 26 weeks. I. butyriciproducens (105 CFU/day) or placebo were given for 12 weeks, then subjects in placebo will start the treatment (105 CFU/day), and the other group will increase the dose (108 CFU/day) for 14 weeks. Overweight or obese patients with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) were included. Patients were assessed for clinical, biochemical, and microbiota parameters at the time of recruitment (V1), after phase 1 (V7) and phase 2 (V10), during which the eating and lifestyle habits were also evaluated. No dietary advice was given. Results. Nineteen have completed the study. Treated patients during the first phase had a significant improvement in glucose-insulin metabolism demonstrated through the HOMA Disposition Index (p= 0.0075). Lipid profile also ameliorates in patients treated at a low dose and then at a high dose, particularly decreasing triglycerides (phase 1: p= 0.0212; phase 2: p= 0.0261). The weight and BMI of patients were stable throughout the period of study. Data from Flash glucose Monitoring (FGM) show a more stable glucose, mainly at the end of the study. Serum AGE concentrations showed a trend towards a decrease in treated patients, whereas IL-10 slowly increased without changes in IL-6 and IL-17.Lastly, 10 out of 19 patients after 26 weeks of treatment had a remission in IFG or IGT (52.6%). Conclusions. Intestinimonas butyriciproducens seems to improve insulin sensitivity and triglycerides in treated patients. Intestinimonas butyriciproducens could be a new strategy in the work-up of T2D prevention. Presentation: 6/1/2024

7007 Analytical & Clinical Performance of a Novel Sensitive Rapid Bioassay for Thyrotropin Receptor Antibodies

Abstract Disclosure: P.D. Olivo: Consulting Fee; Self; QuidelOrtho, CA USA. H. Kim: Employee; Self; QuidelOrtho. L. Miao: Employee; Self; QuidelOrtho. J. Houtz: Employee; Self; QuidelOrtho. M. Luffy: None. J. Wolf: None. G.J. Kahaly: Grant Recipient; Self; QuidelOrtho, USA. Background: The role of stimulatory anti-TSH-R-Ab in the pathogenesis of autoimmune hyperthyroidism is well established. A novel and rapid cell-based bioassay, referred to as Turbo TSITM, for measurement of thyroid-stimulating autoantibodies (TSAb) was recently developed. An assessment of the analytical & clinical performance of this bioassay is described herein. Methods: Turbo TSI greatly reduces the complexity and time required to measure TSAb. It avoids the need for cell culture, has no wash or lysis steps, and has a total turn-around-time of less than 90 minutes. Thawed cells from Turbo TSI kits were treated with different concentrations of a World Health Organization (WHO) international standard (IS) TSI or TSAb-positive serum. TSAb was measured as a function of luciferase activity measured as relative light units (RLU) and converted into international units per liter (IU/L). Two users at two sites performed analytical performance studies on numerous samples, over multiple days. Results: The limit of blank, limit of detection and limit of quantitation were determined to be 0.007 IU/L, 0.014 IU/L, and 0.021 IU/L, respectively. Receiver operator characteristics (ROC) analysis determined the cut-off to be 0.0241 IU/L with an area under the curve of 0.984. The linear range was shown to be from 0.015 to 11.958 IU/L. The intra-laboratory precision was ≤15 percent CV. The overall reproducibility of the assay was ≤20 percent CV for five concentrations (0.06 to 5.16 IU/L). Interference and cross reactivity studies with a variety of substances showed that the assay was robust. Turbo TSI demonstrated 95.2% (95% CI 83.3-98.1) sensitivity and 94.8% (95% CI 90.9-97.1) specificity when compared with an FDA-cleared bioassay (Thyretain® TSI) using serum from 295 patients with autoimmune thyroid disease (AITD). When testing 172 unselected, consecutive TSAb+ AITD patients, a US based, prospective, multicenter, blinded study showed a 98% concordance between Turbo TSI and Thyretain® TSI. When comparing Turbo TSI, Thyretain TSI and a TSH-R-Ab binding immunoassay (Cobas) in 670 unselected, consecutive, treated and untreated AITD subjects, sensitivity was 83%, 79% and 68%, respectively (Turbo vs. Cobas, P<0.001). Furthermore, testing 84 patients with naïve, untreated Graves’ hyperthyroidism, detection of TSH-R-Ab was 100%, 98% and 92%, respectively (Turbo TSI vs binding assay, P<0.01). Finally, 95% vs. 73% of 332 patients with Graves’ orbitopathy were TSH-R-Ab+ with Turbo TSI vs. binding assay (P<0.001). Conclusions: The Turbo TSI bioassay exhibits excellent analytical & clinical performance, a high level of reproducibility, and compares well with the FDA-cleared Thyretain® TSI. Presentation: 6/1/2024

Safety of a 4-Dose 20-Valent Pneumococcal Conjugate Vaccine Series in Infants: A Randomized Trial.

The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection for pneumococcal disease. It contains all 13-valent pneumococcal conjugate vaccine (PCV13) components plus conjugates for 7 additional serotypes. Our primary objective with this study was to evaluate PCV20 tolerability and safety. In this phase 3, multi-country, double-blind study, healthy infants born at ≥34 weeks' gestation were randomly assigned 2:1 to receive PCV20 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety assessments included local reactions and systemic events within 7 days after each vaccination, adverse events (AEs) from dose 1 to 1 month after dose 3 and from dose 4 to 1 month after dose 4, and serious AEs and newly diagnosed chronic medical conditions from dose 1 through 6 months after the last dose. Participants received PCV20 (N = 1000) or PCV13 (N = 504); 91.7% received all 4 doses. The frequencies of local reactions and systemic events were generally similar in PCV20 and PCV13 groups, with most reported as mild or moderate. The most common local reaction was injection site pain (PCV20, 24.7% to 40.5%; PCV13, 26.8% to 42.0%); irritability was the most common systemic event (PCV20, 54.8% to 68.2%; PCV13, 54.7% to 68.5%). AE frequencies were similar in both groups. No serious AEs were related to study vaccines. Few newly diagnosed chronic medical conditions were reported (2.8% in both groups). PCV20 was safe across multiple countries, in late preterm infants, and when administered with other vaccines. A 4-dose series of PCV20 had a tolerability and safety profile similar to that of PCV13.

Microbiota, metabolic profiles and immune biomarkers in infants receiving formula with added bovine milk fat globule membrane: a randomized, controlled trial.

Few studies have evaluated the effects of milk fat globule membrane (MFGM) on microbiota and immune markers in early infant nutrition. In this double-blind randomized study, infants (7-18 days of age) received either bovine milk-based infant formula (Control) or similar formula with an added source (5 g/L) of bovine MFGM (INV-MFGM) for 60 days. A reference group received mother's own human milk over the same period (HM). Oral and stool samples were collected (Baseline and Day 60) to evaluate microbiota, immune markers, and metabolites. At Day 60, stool bacterial diversity and richness were higher in formula groups vs HM, as were Bifidobacterium bifidum and B. catenulatum abundance. Compared to HM, stool pH was higher in Control, while acetate, propionate, isovalerate, and total short- and branched-chain fatty acids were higher in INV-MFGM. Butyrate and lactate increased for INV-MFGM from baseline to Day 60. No group differences in oral microbiota or immune markers (α- and β-defensin, calprotectin, or sIgA) were detected, although sIgA increased over time in all study groups. Added bovine MFGM in infant formula modulated stool microbiota and short- and branched-chain fatty acids compared to human milk; changes were modest relative to control formula. Overall, distinct patterns of stool metabolites and microbiota development were observed based on early nutrition. ClinicalTrials.gov, identifier NCT04059666.

Impact of frenectomy on the oral exercise in patients with ankyloglossia and obstructive sleep apnea: double-blind randomized controlled clinical trials.

This study compares the efficacy of oral exercise alone to oral exercise with frenectomy in improving obstructive sleep apnea (OSA) symptoms and quality of life (QOL) in patients with ankyloglossia. A prospective, controlled, double-blind clinical study enrolled fifteen adults (20-60 years) newly diagnosed with mild to moderate OSA and ankyloglossia. Participants were randomly assigned to either oral exercise alone (control group; n = 8) or oral exercise with frenectomy (intervention group; n = 7). Outcomes were assessed after a 3-month therapy period using polysomnography, the Epworth Sleepiness Scale (ESS), tongue strength (measured in kPa), and QOL questionnaires. Both control (-2.88 ± 1.73; p = 0.02) and intervention (-4.00 ± 3.65; p = 0.03) groups showed a significant reduction in ESS scores, indicating both improved sleepiness. Although the apnea-hypopnea index (AHI) increased in both groups after treatment, these changes were not statistically significant (control 4.73 ± 15.55; p = 0.48, intervention 10.42 ± 14.66; p = 0.12). Tongue strength significantly increased in both groups: control group (p = 0.04) and intervention group (p = 0.03). Satisfaction rates with the overall treatment process were 100% in the control group and 57.1% in the intervention group. Furthermore, 75.0% and 57.1% of participants in the respective groups reported an improvement in QOL. Frenectomy improved tongue mobility and the ability to perform oral exercises in individuals with OSA and ankyloglossia. However, these exercises did not significantly improve OSA-related symptoms or QOL. While frenectomy enhances tongue mobility, thereby enabling better engagement in oral exercises. These exercises alone did not significantly improve OSA-related symptoms or QOL. This suggests that oral exercises focusing solely on tongue mobility may not be sufficient for managing OSA. The Thai Clinical Trials Registry was TCTR20220429002.

Endogenous pain modulation after sleep restriction in migraine: a blinded crossover study

BackgroundPatients with migraine are vulnerable to insufficient sleep, but the impact of sleep restriction is largely unknown. In addition, the importance of sleep may be different in patients with migraine who mostly have attack onsets during sleep, so called sleep-related migraine, compared to patients with non-sleep-related migraine. In this study we investigate the effect of sleep restriction on endogenous pain modulation in patients with migraine and healthy controls. We also compared the effect of sleep restriction in sleep-related and in non-sleep-related migraine.MethodsMeasurements were conducted in 39 patients with migraine between attacks and 31 controls, once after habitual sleep and once after two consecutive nights of partial sleep restriction. There were 29 and 10 patients with non-sleep-related and sleep-related migraine respectively. Test stimulus was 2-min tonic noxious heat to the left volar forearm. Temporal summation was calculated as the regression coefficient for rated pain in the late part of this 2-min stimulation. Conditioning stimulus was right hand-immersion in 7 °C water. Conditioned pain modulation was defined as the difference in rated pain with and without the conditioning stimulus and was calculated for temporal summation and mean rated pain for the test stimulus. The effect of sleep restriction on temporal summation and conditioned pain modulation was compared in migraine subjects and controls using two-level models with recordings nested in subjects.ResultsConditioned pain modulation for temporal summation of heat pain tended to be reduced after sleep restriction in patients with migraine compared to controls (p = 0.060) and, in an exploratory analysis, was reduced more after sleep restriction in sleep-related than in non-sleep-related migraine (p = 0.017). No other differences between groups after sleep restriction were found for temporal summation or conditioned pain modulation.ConclusionPatients with migraine may have a subtly altered endogenous pain modulation system. Sleep restriction may have an increased pronociceptive effect on this system, suggesting a mechanism for vulnerability to insufficient sleep in migraine. This effect seems to be larger in sleep-related migraine than in non-sleep-related migraine.

The effect of Traumeel LT ad us. vet. on the perioperative inflammatory response after castration of stallions: a prospective, randomized, double-blinded study.

Stallion castration is a standard procedure with a risk of post-surgical complications. Castration induces an acute phase response (APR). Serum Amyloid-A (SAA) is a well-studied major acute phase protein (APP), that has been shown to be a good marker for the development of post-surgical complications. The current gold standard for reducing the APR after castration is Flunixin-Meglumin, which is a non-steroidal anti-inflammatory drug (NSAID) inhibiting COX1/2. In contrast, Traumeel LT ad us. vet. can modulate the APR by induction of the inflammation resolution. The aim of this study was to compare the effect of Flunixin-Meglumin and Traumeel LT ad us. vet. on the acute phase response. A total of 60 stallions were recruited and 54 stallions entered the study with 27 stallions in each treatment group. The stallions were treated pre- and postoperatively with either Flunixin-Meglumin (FL) or with Traumeel LT ad us. vet. (TR). Blood was taken before and 24 h, 48 h and 72 h after castration. The following main parameters were assessed: SAA, fibrinogen, iron, white blood cells, neutrophils, Interleukin1ß, and cortisol. Wound healing and pain were assessed at 8 time points. The main variable SAA was increased after surgery reaching a mean value of 122 µg/ml in the FL group and a mean SAA of 226 µg/ml in the TR group 48 h after surgery, reaching a significant difference only at the 24 h timepoint (p = 0.03). All stallions had the highest pain summary score 8 hours after surgery, with decreasing values thereafter. The pain scores were not statistically different at any time point. In the FL group five stallions developed a suture dehiscence compared to only one stallion in the TR group (p = 0.001). Within the limitations of this study, Traumeel LT ad us. vet. seems to have proresolving effects on the inflammation induced by surgery making it a valuable treatment to reduce the APR induced by castration. Due to its different mode of action, Traumeel LT ad us. vet. might be an alternative treatment option if gastrointestinal side effects or renal side effects of NSAIDs should be avoided. Further studies are needed combining Traumeel LT ad us. vet. and Flunixin.

A-241 Verification and Validation Study for a Host Response Assay Based on TRAIL, IP-10, and CRP: Application to Pediatric Emergency Department

Abstract Background Acute febrile illnesses (AFIs) represent a significant disease burden globally; however, the lack of reliable, rapid point-of-care testing makes diagnosis difficult. A simple tool for distinguishing bacterial versus non-bacterial infections would radically improve patient management and reduce indiscriminate antibiotic use. MeMed BV® (MMBV) is a blood test to reliably differentiate between viral and bacterial infections. Three host proteins (TRAIL, IP-10, and CRP) are measured quantitatively and a combinational score (0-100) is computed that indicates the likelihood of bacterial infection (or co-infection) versus viral infection (BV Score). MMBV time to result is 15 min on the MeMed Key® analyzer that conducts chemiluminescence-based immunoassays to measure protein concentrations and calculates the test score, using 100 µL of serum. Methods The verification study design was a comparison of known results to on-site testing for contrived samples. The validation study design was a prospective, single-center, observational, blinded diagnostic accuracy study conducted between 8/3/22 to 5/30/23. The population was pediatric patients with suspected serious infections presenting to Geisinger’s quaternary care Pediatric Emergency Dept. in Danville, PA. The comparator was a clinical chart review and adjudication of over 60 clinical and laboratory variables related to systemic infections. The data review team consisted of one pediatric emergency department physician, one pediatric infectious disease physician, and one microbiology laboratory director. If clinical decisions differed among the three, the team adjudicated with a full chart review including knowledge of the eventual outcome, which served as the final reference standard result. The study aims were to assess the analytical and clinical accuracy of MMBV testing and to assess the test’s potential impact to further inform the provider’s decision to admit or discharge the patient. Results Of 60 contrived samples there was three failed tests (5% failure rate) and 2 discordant results. Analytical accuracy was 55/57 (96.5%) for 28 bacterial, 26 viral, and 1 equivocal control. Of 50 pediatric patients recruited, 8 were excluded because they were trauma patients. Among 42 patients tested, 22/42 (52.4%) were interpreted as bacterial or co-infection, 16/42 (38.1%) as viral or non-infectious, and 4/42 (9.5%) as equivocal. For 37/38 (97.3%) of patients with bacterial/viral MMBV results, the result was concordant with expert adjudication. Of the 42 patients for which potential utility was assessed, all results were in alignment with the clinical decisions made for admission or discharge. Conclusions MMBV performed accurately in pediatric ED patients with symptoms of severe infection, both clinically and analytically. A larger sample size will be tested to assess the utility in ED admission and discharge decisions and antimicrobial stewardship. The prevalence of viral and bacterial or coinfection cases within the sample population is representative of the pediatric population samples.

B-308 Analytical and clinical performance of a novel ovarian cancer screening test in asymptomatic women

Abstract Background Ovarian cancer (OC) ranks among the deadliest gynecological cancers, often diagnosed at advanced stages when treatment options are limited. Costly sequencing methods and established immunoassay and imaging-based methods lack early-stage sensitivity, highlighting the need for a cost-effective test with improved performance. Extracellular vesicles (EVs) produced in abundance by all cells can potentially improve test sensitivity and detection of multiple colocalized cancer specific markers can improve test specificity. The randomized controlled trial UKCTOCS (United Kingdom Collaborative Trial of Ovarian Cancer Screening) where over 200,000 postmenopausal asymptomatic women were randomly assigned to three arms revealed no significant reduction in mortality with OC screening. We report on an EV-based OC Test performance in serum samples from asymptomatic postmenopausal women in UKCTOCS. Methods The OC Test was previously locked (biomarkers, method, cutoff) and validated in an independent cohort. We evaluated the OC Test in a blinded case-control study nested within the no screening (NS) and annual ultrasound screening (USS) arms of UKCTOCS. All UKCTOCS participants provided a blood sample at study entry. Cases were all women who developed high grade serous ovarian cancer (HGSOC) within 36 months following sample donation (spun within 28 hours). They were matched by age at collection (+/-2 years) to women who had no OC detected either before or within the trial follow up period (controls). Where a case had >1 sample within the 0-36 months period, the control sample was matched to the case sample closest to diagnosis. The OC Test was run with a locked method and classifier algorithm utilizing 3 independent biomarker combinations tested in duplicate. OC Test results were calculated based on a previously determined cutoff prior to unblinding of clinical outcomes. Run controls were prepared by harvesting conditioned media from COV413A cell cultures (an ovarian epithelial-serous carcinoma cell line), purifying EVs and spiking into pre-screened OC Test negative human plasma at three levels. Run controls were run twice per day, one replicate per run for 17 days. Results We retrospectively assessed 116 samples from 108 cases (63 clinical Dx NS, 15 clinical Dx USS, 30 screen detected USS) women with HGSOC and 1310 samples from 1310 controls. OC test sensitivity for HGSOC was 84% (36/43; 95% CI 69%-93%), Stage I/II sensitivity was 89% (8/9; 95% CI 51%-99%) and the AUC (area under the curve) was 0.93 for case samples drawn 0-12 months prior to clinical Dx and all control samples. The OC Test specificity was 98% (1099/1176, 95% CI 97%-98%). Within laboratory CVs were 20.9%, 12.7% and 0.6% for low negative, high negative and high positive run controls respectively. Data from 143 samples (10%, 9 cases, 134 controls) were excluded due to operator error, low sample volume or quality issues. Conclusions The OC Test is capable of highly sensitive detection of HGSOC within one year of clinical diagnosis including at the earliest stages of disease while maintaining exceptionally high specificity. The results demonstrate the potential application of the OC Test for ovarian cancer screening in asymptomatic women.

Longitudinal monitoring of hypertonia through a multimodal sensing glove

As clinical evaluations of neuromuscular disorders such as hypertonia mostly rely on perception-based scales, the imprecise subjective ratings make it difficult to accurately monitor treatment progress. To promote objective evaluation, this work used a multi-modal sensing glove in a double-blind study to enable sensitive monitoring of medication effects across 19 participants. The biomechanical measurements from the sensing glove effectively distinguished patient cohorts receiving a baclofen treatment or a placebo with 95% confidence. Consistent monitoring over a two-month period was demonstrated, closely tracking variations in individual responses to treatment. The biomechanical changes were correlated to neural activities as recorded by electromyography, verifying the medication effects. The sensing glove is shown to be a reliable tool for point-of-care settings to facilitate precise evaluation of hypertonia, essential for tailoring individual treatment choices and timely management of chronic symptoms.

Ropivacaine and magnesium sulfate in sciatic nerve block at the popliteal level: randomized double-blind study.

Following surgical procedures, over 80% of patients experience acute pain, with half of them expressing dissatisfaction with pain relief. The modern approach to surgical treatment and pain management increasingly relies on implementing multimodal analgesia, which includes the use of adjuvants in addition to long-acting local anesthetics (such as ropivacaine). This double-blind randomized study evaluated the analgesic effect of magnesium sulfate added to ropivacaine in the sciatic nerve block at the popliteal level for bunion correction surgery. In this double-blind study, fifty patients were enrolled and randomized in a 1:1 ratio to receive ropivacaine and MgSO<inf>4</inf> 200 mg or ropivacaine and physiological solution. The primary endpoint was the duration of sensory block. A statistically significant difference was observed in the onset time for sensory block (9.2 minutes vs. 21.8 minutes, P<0.001) and its duration (18.2 hours vs. 13.9 hours, P<0.001) between the two groups. Between 12 and 24 hours postoperatively, the maximum NRS pain scores in the magnesium group were lower than those in the control group (IQR [range]) 2 (2-3.8 [0-6.5]) vs. 6.7 (5.6-7.9 [2.7-9.2], P<0.001). The need for additional opioids after 12-24 hours was significantly higher in patients in the physiological solution group compared to those in the magnesium group. Our results suggest that magnesium added to the local anesthetic extends sensory block duration, reduces postoperative pain, improves the quality of analgesia, decreases the need for additional opioids. Further studies are needed to confirm these preliminary findings.