An in vitro evaluation of intravenous lipid emulsion on three common canine toxicants.

Objective: To determine whether intravenous lipid emulsion (ILE) therapy significantly reduces the concentration of baclofen, ibuprofen, and/or bromethalin in canine whole blood over time. Animals: Seven 500 mL bags of canine DEA 1.1 negative blood were divided into aliquots of 125 mL and randomly assigned to one of three treatment groups (baclofen, ibuprofen, bromethalin) or four control groups (a positive control for each treatment group and a negative control group). Procedures: Injectable ibuprofen (200 mg/kg), baclofen (8 mg/kg), or bromethalin (3 mg/kg) was apportioned into 125 mL aliquots of canine whole blood and incubated for 30 min at 38.5°C. ILE (12.4 mL, Intralipid® ) was added to each sample and the solution vortexed [215 rpm for 15 min at 37°C (98.6°F)]. Samples were obtained at designated time points (0, 15, 30, 60, 180, 360 min), centrifuged, and separated into serum and RBC fractions. Serum samples were ultracentrifuged (22,000 g for 10 min at 37°C) to separate lipid rich and poor fractions. Samples were stored at -80°C prior to analysis. Results: A significant decrease in total drug concentration was established for bromethalin and its metabolite desmethylbromethalin compared to positive controls. ILE significantly reduced desmethylbromethalin at the 30-and 360-min time points. The remainder of the desmethylbromethalin time points did not reach significance. Bromethalin concentration was significantly reduced at all time points compared to positive controls. Neither baclofen nor ibuprofen had significant changes in concentration. Conclusion: ILE therapy was effective at reducing the total drug concentration of bromethalin and its metabolite desmethylbromethalin supporting the lipid sink theory. As a single compartment in vitro study, this study does not evaluate other proposed mechanisms of action of ILE therapy. ILE therapy may have other means of significantly decreasing lipophilic drug concentration in cases of toxicosis.

Timing of intravenous immunoglobulin treatment and outcome in Guillain-Barré syndrome: Is time nerve?

INTRODUCTION/AIMS: Despite treatment, a considerable proportion of patients with Guillain-Barré syndrome (GBS) experience poor recovery, highlighting a therapeutic need. There is a lack of evidence that treatment timing affects recovery. This study aims to investigate the effects of intravenous immunoglobulin (IVIg) timing on disability and speed of recovery in GBS. METHODS: We performed a retrospective study of 136 IVIg-treated GBS patients admitted to two Korean centers between 2010 and 2021. We analyzed the effect of time to IVIg on the GBS disability scale (GBS-DS) and the degree of improvement from nadir (∆GBS-DS) at 1, 3, 6, and 12 months, as well as the time to regain the ability to walk or run unaided. Time to IVIg was treated either as a continuous variable or categorized into 1-week intervals to explore critical time windows. Known prognostic factors, the modified Erasmus GBS Outcome Scores on admission and pre-treatment serum albumin levels were adjusted as covariates. RESULTS: Shorter time to IVIg was independently associated with better GBS-DS, greater ∆GBS-DS, and shorter time to walk or run unaided at all time points. The therapeutic effect of IVIg was notably diminished when administered beyond the first 2 weeks of onset. DISCUSSION: Our study highlights the timing of IVIg as a modifiable prognostic factor in GBS. The earlier IVIg is initiated, the better the outcomes, with the ideal time window being within the first 2 weeks. These findings underscore the importance of prompt diagnosis and early intervention to optimize recovery in GBS patients.

Prospective case-control study on pain intensity after the use of promethazine in patients undergoing videothoracoscopy.

Objective: Effective and secure pain management following video-assisted thoracoscopic surgery (VATS) is crucial for rapid postoperative recovery. This study evaluated analgesic and sedative effects of sufentanil and promethazine in patient-controlled intravenous analgesia (PCIA) post-thoracic surgery, along with potential adverse reactions. Methods: In this prospective, randomized, controlled, double-blind, clinical study, 60 patients (American Society of Anesthesiologists status I-III) undergoing VATS were enrolled. The patients were randomized into experimental (Group P) or control (Group C) groups. PCIA was administered post-general anesthesia using a double-blind method. Group P received sufentanil (3 µg/kg) + promethazine (1 mg/kg) + 0.9% sodium chloride solution (100 mL total), while Group C received sufentanil (3 µg/kg) + 0.9% sodium chloride solution (100 mL total). PCIA settings included a 1-mL bolus and 15-min locking time. The primary outcomes were the visual analog scale (VAS) at rest and during coughing and sedation (Ramsay) scores at 6, 12, 24, and 48 h. The secondary outcomes were rescue drug use rate, hemodynamic parameters (mean arterial pressure and heart rate), percutaneous oxygen saturation, respiratory rate, and occurrence of adverse reactions. Results: Group P exhibited lower resting and coughing VAS scores at 6, 12, 24, and 48 h, plus decreased incidence of nausea and vomiting within 48 h post-surgery compared with Group C (p < 0.05). No significant differences were observed in pruritus, sedation (Ramsay) scores, mean arterial pressure, heart rate, oxygen saturation, or respiratory rate between the two groups (p > 0.05). Discussion: The combination of sufentanil and promethazine for postoperative intravenous analgesia could effectively reduce adverse effects such as nausea and vomiting, contributing to postoperative pain relief.

Pain and immune function in patients undergoing gastric cancer surgery following stellate ganglion block with total intravenous anesthesia.

BACKGROUND: Stellate ganglion block is a commonly used sympathetic nerve block technique that restores the balance of the sympathetic and vagal nervous systems of the body and inhibits sympathetic nerve activity. AIM: To analyze the effect of a stellate ganglion block combined with total diploma intravenous anesthesia on postoperative pain and immune function in patients undergoing laparoscopic radical gastric cancer (GC) surgery to provide a reference basis for the formulation of anesthesia protocols for radical GC surgery. METHODS: This study included 112 patients who underwent laparoscopic radical surgery for GC between January 2022 and March 2024. There was no restriction on sex. The patient grouping method used was a digital random table method, and the number of cases in each group was 56. The control group was administered total intravenous anesthesia, and the observation group compounded the stellate ganglion block according to the total intravenous anesthesia protocol. Postoperative hemodynamics, pain levels, and immune indices were compared between the groups. RESULTS: The heart rate and mean arterial pressure in the observation group after intubation were lower than those in the control group (P < 0.05). Pain levels were compared between the two groups at 2 hours, 12 hours, 24 hours, and 48 hours after surgery (P > 0.05). The number of CD3+, CD4+, and CD4+/CD8+ cells at the end of surgery was higher in the observation group than in the control group, and the number of CD8+ cells was lower in the observation group than in the control group (P < 0.05). There were no significant differences between the two groups in terms of propofol dosage, awakening time, extubation time, or postoperative adverse reactions (P > 0.05). CONCLUSION: The application of a stellate ganglion block combined with total intravenous anesthesia had no significant effect on postoperative pain levels in patients undergoing laparoscopic radical GC surgery. However, it can safely reduce the effect of surgery on the immune function of patients and is worth applying in clinical practice.

Use of tissue adhesive for neonatal intravenous access devices: A scoping review.

Neonates often require vascular access devices for medication or fluid therapy, but a third of devices fail before treatment completion or end with a complication. For adults and children, securing these devices with tissue adhesive (TA) increases the dwell and reduces complications. However, there is a lack of evidence for the neonatal population. This scoping review aimed to assess the evidence of TA for vascular access devices in neonates. The Arksey and O'Malley's (2005) framework was used. The inclusion criteria covered studies published from 2007 (when TA was first reported for use in vascular access devices) to June 2024, available in English, Portuguese, and Spanish, across six databases. Two independent reviewers assessed the studies using Covidence software, with a third reviewer resolving conflicts. Quality assessment was performed using the Mixed Methods Appraisal Tool. From 981 identified studies, 12 were included. Most studies (n = 5, 41.7%) enrolled between 100 and 500 neonates with vascular access devices. Publications originated from four regions and were observational studies (n = 6, 50%), quasi-experimental (n = 3, 25%), and case series (n = 2, 16.7%) with one randomized controlled trial (8.3%) focusing on umbilical venous catheters (UVC). The most common TA composition used was a combination of n-butyl- and 2-octyl- cyanoacrylate (n = 4, 33.3%). The amount of TA applied varied across studies, and often TA was part of a bundle (n = 7, 58.3%). Most studies applied TA to central venous access devices (n = 10, 83.3%) and 2 (16.7%) in peripheral devices. Although there was variation in device failure, the studies generally indicated a reduction in complications such as dislodgment (central catheter: 11.3% [peripherally inserted central catheter {PICC}] to 24.6% [UVC] in non-TA group vs 0.7% [PICC] to 7.7% [UVC] in TA group), device-associated bloodstream infections (central: 7.7% [UVC] and incidence of 2.76/1000 catheter days [PICC] in non-TA group vs 3.1% [UVC] and incidence of 0.99/1000 catheter day [PICC] in TA group), and phlebitis (13% in non-TA group vs 3% in TA-group), as well as increased dwell time in peripheral catheters. Most studies included both term and preterm neonates but did not differentiate between them in their analyses. Skin assessment, life of first dressing, and follow-up of catheters and patients were not reported in most studies. CONCLUSION: TA may reduce complications in vascular access devices, but the evidence in neonates is limited and varied. Many studies include TA as part of bundle, making it difficult to isolate its effects. Additionally, the current evidence lacks robustness due to the design limitations of the studies. Future research should focus on randomized controlled trials to evaluate TA's effectiveness and safety in preventing device failures and complications in neonates, considering different subgroups, to ensure the safety of TA in these nuanced populations. WHAT IS KNOWN: • Research in adults and pediatrics provides evidence supporting the use of tissue adhesive (TA) for vascular access devices, showing a positive impact in reducing failures and complications. • The use of TA in neonates needs to be carefully considered due to their unique characteristics. WHAT IS NEW: • There is a gap in the literature on the use of TA for securing vascular access devices in neonates, particularly regarding its safety and effectiveness in preventing failures and complications. • Further studies are needed to provide robust evidence verifying the effectiveness and safety of TA in this population.

The association between serum S100ß levels and prognosis in acute stroke patients after intravenous thrombolysis: a multicenter prospective cohort study.

BACKGROUND: S100ß is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100ß and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. METHODS: Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100ß levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. RESULTS: A total of 1072 patients were included in the analysis. The highest S100ß levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100ß level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: ß 36.853, 95% confidence interval (CI) 22.659-51.048, P < 0.001; non-dominant: ß 23.645, 95% CI 10.774-36.516, P = 0.007). However, serum S100ß levels at 24 h were more strongly associated with NIHSS scores at 24 h and 3-month unfavorable outcome in patients with dominant hemisphere stroke (NIHSS: ß 3.470, 95% CI 2.392-4.548, P < 0.001; 3-month outcome: odds ratio (OR) 5.436, 95% CI 2.936-10.064, P < 0.001) than in those with non-dominant hemisphere stroke (NIHSS: ß 0.326, 95% CI  - 0.735-1.387, P = 0.547; 3-month outcome: OR 0.882, 95% CI 0.538-1.445, P = 0.619). The association of S100ß levels and HT was not significant in either stroke lateralization group. CONCLUSIONS: Serum S100ß levels 24 h after IVT were independently associated with HT, infarct volume, and prognosis in patients with IVT, which suggests the application value of serum S100ß in judging the degree of disease and predicting prognosis.

Successful Treatment of Refractory Cutaneous Manifestations of Dermatomyositis With Intravenous Immunoglobulin: A Case Report.

Dermatomyositis is a connective tissue disorder with dermatological and extracutaneous manifestations. Multiple treatment modalities have been used to treat dermatomyositis, and there have been cases with resistant disease refractory to conventional therapies. Corticosteroids are usually used to achieve remission, and from then, steroid-sparing agents such as azathioprine are used to maintain remission. However, in this report, we present a case of dermatomyositis with refractory cutaneous manifestation. The patient's muscular pain had subsided with the use of corticosteroids, but the dermatological lesions did not respond to multiple treatment modalities, responding only to intravenous immunoglobulins (IVIG).

Atypical Infective Endocarditis Presenting With Euthermia and Right Lower Quadrant Abdominal Pain.

Infectious endocarditis (IE) is an infection of the heart's endothelial lining, often stemming from an underlying bacteremia. High-risk populations include intravenous substance users, individuals with structural heart disease, those with intravascular devices, and those with prosthetic heart valves. In the emergency department, IE is often suspected in patients with a fever, known risk factors, and unexplained systemic symptoms due to systemic thromboemboli. We present a case of atypical IE occurring in an afebrile 38-year-old woman with a remote history of intravenous drug use. The patient's clinical presentation was characterized by systemic inflammatory response syndrome, stabbing-like right lower quadrant abdominal pain radiating to the right lower back and the rest of the abdomen, malaise, fatigue, and an absence of a fever. A CT scan revealed a right renal embolism and an infarcted right kidney, prompting a bedside point-of-care echocardiogram that showed a large vegetation on the mitral valve, suggestive of IE with systemic thromboembolic disease. The patient received broad-spectrum antibiotics and antipyretics and ultimately underwent mitral valve replacement, with good recovery upon discharge. Patients with IE are at high risk for life-threatening complications due to tissue damage from systemic microemboli and sepsis. It is important to identify IE's atypical presentation and risk factors for early recognition, prompt point-of-care echocardiogram, and initiation of treatment. This is particularly important in the era of increased opioid use among our patient population which could potentially conceal an underlying fever.

Intravenous lidocaine infusion therapy and intraoperative neurophysiological monitoring in adolescents undergoing idiopathic scoliosis correction: A retrospective study.

BACKGROUND: Posterior spinal instrumentation and fusion is an established surgical procedure for the correction of adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring is standard practice for this procedure. Anesthetic agents can have different, but significant, effects on neurophysiological monitoring outcomes. AIM: To determine if intravenous lidocaine infusion therapy has an impact on the intraoperative neurophysiological monitoring during posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis. METHODS: Following ethical approval, we conducted a retrospective review of charts and the archived intraoperative neurophysiological data of adolescents undergoing posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis. Intraoperative neurophysiological monitoring data included the amplitude of motor evoked potentials and the amplitude and latency of somatosensory evoked potentials. A cohort who received intraoperative lidocaine infusion were compared to those who did not. RESULTS: Eighty-one patients were included in this analysis, who had surgery between February 4, 2016 and April 22, 2021: 39 had intraoperative intravenous lidocaine infusion and 42 did not. Based on hourly snapshot data, there was no evidence that lidocaine infusion had a detrimental effect on the measured change from baseline for MEP amplitudes in either lower (mean difference 41.9; 95% confidence interval -304.5 to 388.3; p = .182) or upper limbs (MD -279.0; 95% CI -562.5 to 4.4; p = .054). There was also no evidence of any effect on the measured change from baseline for SSEP amplitudes in either lower (MD 16.4; 95% CI -17.7 to 50.5; p = .345) or upper limbs (MD -2.4; 95% CI -14.5 to 9.8; p = .701). Finally, there was no evidence of a difference in time to first reportable neurophysiological event (hazard ratio 1.13; 95% CI 0.61 to 2.09; p = .680). CONCLUSIONS: Data from these two cohorts provide preliminary evidence that intravenous lidocaine infusion has no negative impact on intraoperative neurophysiological monitoring during PSIF for adolescent idiopathic scoliosis.

Cytokine landscape in hospitalized children with multisystem inflammatory syndrome.

The etiology of multisystem inflammatory syndrome in children (MIS-C), frequently observed following COVID-19 infection, remains elusive. This study unveils insights derived from cytokine analysis in the sera of MIS-C patients, both before and after the administration of intravenous immunoglobulin (IVIG) and glucocorticosteroids (GCS). In this study, we employed a comprehensive 45-cytokine profile encompassing a spectrum of widely recognized proinflammatory and antiinflammatory cytokines, as well as growth factors, along with other soluble mediators. The analysis delineates three principal cytokine-concentration patterns evident in the patients' sera. Pattern no.1 predominantly features proinflammatory cytokines (IL-6, IL-15, IL-1ra, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor α (TNFα), C-X-C motif chemokine ligand 10 (CXCL10/ IP-10), and IL-10) exhibiting elevated concentrations upon admission, swiftly normalizing post-hospital treatment. Pattern no. 2 includes cytokines (IL-17 A, IL-33, IFNγ, vascular endothelial growth factor (VEGF), and programmed death ligand (PD-L1)) with moderately elevated levels at admission, persisting over 7-10 days of hospitalization despite the treatment. Pattern no. 3 comprises cytokines which concentrations escalated after 7-10 days of hospitalization and therapy, including IL-1α, IL-1ß, IL-2, IL-13, platelet-derived growth factor AA/BB (PDGF AA/BB). The observed in cytokine profile of MIS-C patients showed a transition from acute inflammation to sustaining inflammation which turned into induction of humoral memory mechanisms and various defense mechanisms, contributing to recovery.

Intravenous Tranexamic Acid for Control of Bleeding during External Dacryocystorhinostomy under General Anesthesia: A Randomized Clinical Trial.

Purpose: To investigate the effect of intravenous tranexamic acid administered prior to external dacryocystorhinostomy (DCR) surgery to decrease intraoperative bleeding under general anesthesia. Methods: This was a double-blinded randomized placebo-controlled trial. A total of 70 patients (35 intervention and 35 control) with nasolacrimal duct obstruction (NLDO) who were selected for DCR surgery between September 2021 and September 2022 were included. After clinical examinations and laboratory tests, patients were randomly classified into intervention and control groups. The intervention group received 10 mg/kg intravenous tranexamic acid to a maximum dose of 1 gr 30 minutes before the surgery. Controls received normal saline solution as a placebo. The amount of intraoperative bleeding and surgical time were compared between the two groups. Results: The intervention group included 21 men (60%) and 14 women (40%), while the control group included 19 men (54.3%) and 16 women (45.7%). The mean ages of the participants were 55.46 ± 10.8 years and 58.06 ± 11.28 years in the intervention and control groups, respectively. A significant difference was observed between the two groups in the surgical time analysis (control group: 37.74 ± 9.52 minutes vs intervention: 26.03 ± 10.5 minutes; P < 0.001). Additionally, there was a significant difference in the bleeding volume between the intervention (70.66 ± 48.19 ml) and control (47.74 ± 60 ml) groups (P < 0.001). Conclusion: Intravenous tranexamic acid administration before the DCR procedure can successfully control bleeding during the surgery.

Treatment Challenges and Controversies in the Management of Critically Ill Diabetic Ketoacidosis (DKA) Patients in Intensive Care Units.

This review discusses the challenges and controversies in the treatment of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Key areas include the selection of intravenous (IV) fluids, insulin therapy, strategies for preventing and monitoring cerebral edema (CE) by managing hyperglycemia overcorrection, electrolyte replacement, timing of nutrition, use of IV sodium bicarbonate, and airway management in critically ill DKA patients. Isotonic normal saline remains the standard for initial fluid resuscitation, though balanced solutions have been shown to have faster DKA resolution. Current guidelines recommend using continuous IV insulin for DKA management after fluid status has been restored potassium levels have been achieved and subcutaneous (SQ) insulin is started only after the resolution of metabolic acidosis. In comparison, the British guidelines recommend using SQ insulin glargine along with continuous regular IV insulin, which has shown faster DKA resolution and shorter hospital stays compared to continuous IV insulin alone. Although rare, rapid overcorrection of hyperglycemia with fluids and insulin can lead to CE, seizures, and death. Clinicians should be aware of risk factors and preventive strategies for CE. DKA frequently involves multiple electrolyte abnormalities, such as hypokalemia, hypophosphatemia, and hypomagnesemia and regular monitoring is essential for DKA management. Early initiation of oral nutrition has been shown to reduce intensive care unit and overall hospital length of stay. For impending respiratory failure, Bilevel positive airway pressure is not recommended due to aspiration risks. Instead, intubation and mechanical ventilation, with monitoring and management of acid-base and fluid status, are recommended. The use of sodium bicarbonate is discouraged due to the potential for worsening ketosis, hypokalemia, and risk of CE. However, IV sodium bicarbonate can be considered if the serum pH falls below 6.9, or when serum pH is less than 7.2 and/or serum bicarbonate levels are below 10 mEq/L, pre-and post-intubation, to prevent metabolic acidosis and hemodynamic collapse that occurs from apnea during intubation. Managing DKA and HHS in critically ill patients includes using balanced IV fluid solutions to restore volume status, followed by continuous IV insulin, early use of SQ glargine insulin, electrolyte replacement, and monitoring, CE preventive strategies by avoiding hyperglycemia overcorrection, early nutritional support, and appropriate airway management.

Optimizing Microfluidic Channel Design with High-Performance Materials for Safe Neonatal Drug Delivery.

INTRODUCTION: Designing the microfluidic channel for neonatal drug delivery requires proper considerations to enhance the efficiency and safety of drug substances when used in neonates. Thus, this research aims to evaluate high-performance materials and optimize the channel design by modeling and simulation using COMSOL multiphysics in order to deliver an optimum flow rate between 0. 3 and 1 mL/hr. METHOD: Some of the materials used in the study included PDMS, glass, COC, PMMA, PC, TPE, and hydrogels, and the evaluation criterion involved biocompatibility, mechanical properties, chemical resistance, and ease of fabrication. The simulation was carried out in the COMSOL multiphysics platform and demonstrated the fog fluid behavior in different channel geometries, including laminar flow and turbulence. The study then used systematic changes in design parameters with the aim of establishing the best implementation models that can improve the efficiency and reliability of the drug delivery system. The comparison was based mostly on each material and its appropriateness in microfluidic usage, primarily in neonatal drug delivery. The biocompatibility of the developed materials was verified using the literature analysis and adherence to the ISO 10993 standard, thus providing safety for the use of neonatal devices. Tensile strength was included to check the strength of each material to withstand its operation conditions. Chemical resistance was also tested in order to determine the compatibility of the materials with various drugs, and the possibility of fabrication was also taken into consideration to identify appropriate materials that could be used in the rapid manufacturing of the product. RESULTS: The results we obtained show that PDMS, due to its flexibility and simplicity in simulation coupled with more efficient channel designs which have been extracted from COMSOL, present a feasible solution to neonatal drug delivery. CONCLUSION: The present comparative study serves as a guide on the choice of materials and design of microfluidic devices to help achieve safer and enhanced drug delivery systems suitable for the delicate reception of fragile neonates.

Safety and pharmacokinetic properties of a new formulation of parenteral artesunate in healthy Thai volunteers.

BACKGROUND: Parenteral artesunate is the first-line therapy for severe malaria. Artesunate, in its current formulation, must be prepared immediately before administration by first dissolving in sodium bicarbonate solution and then diluting in saline. A novel solvent for rapid and stable single step reconstitution of artesunate was recently developed showing improved solubility and stability. This study aimed to compare the safety and pharmacokinetic properties of the currently available and newly developed parenteral formulation of artesunate in healthy Thai volunteers. METHODS: This was an open-label, randomized, 4 periods, 4-treatments, 24-sequence, single-dose, cross-over study in 72 male and female healthy Thai volunteers. Frequent pharmacokinetic samples were collected in all volunteers at each dose occasion. Observed concentration-time profiles were analysed with a non-compartmental approach followed by a bioequivalence evaluation. RESULTS: Both intramuscular and intravenous administrations of the new parenteral formulation of artesunate were safe and well-tolerated, with no additional safety signals compared to the currently used formulation. The pharmacokinetic properties of artesunate and its active metabolite, dihydroartemisinin, were well-characterized, and showed rapid conversion of artesunate into dihydroartemisinin. Intramuscular administration of the newly formulated artesunate resulted in almost complete bioavailability of dihydroartemisinin. The pharmacokinetic properties were similar between the old and new formulation. CONCLUSIONS: The new and more easily prepared formulation of artesunate was safe and well-tolerated, with similar pharmacokinetic properties compared to the currently used formulation. Dihydroartemisinin, the active metabolite responsible for the majority of the anti-malarial effect, showed equivalent exposure after both intravenous and intramuscular administration of artesunate, suggesting that both routes of administration should generate comparable therapeutic effects. TRIAL REGISTRATION: The study was registered to clinicaltrials.gov (#TCTR20170907002).

Lung ultrasound assessment of atelectasis following different anesthesia induction techniques in pediatric patients: a propensity score-matched, observational study.

INTRODUCTION: Atelectasis is a well-documented complication in pediatric patients undergoing general anesthesia. Its incidence varies significantly based on surgical procedures and anesthesia techniques. Inhalation induction, commonly used to avoid the discomfort of venipuncture, is suspected to cause higher rates of respiratory complications, including atelectasis, compared to intravenous induction. This study aimed to evaluate the impact of inhalation versus intravenous anesthesia induction on atelectasis formation in pediatric patients, as assessed by lung ultrasound (LUS). METHODS: This propensity score-matched observational study was conducted at a tertiary pediatric hospital in Milan, Italy. Inclusion criteria were children ≤ 18 years undergoing elective surgery with general anesthesia. Patients were divided into inhalation and intravenous induction groups. LUS was performed before and after anesthesia induction to assess lung aeration. The primary endpoint was the global LUS score post-induction, with secondary endpoints including the incidence and distribution of atelectasis. RESULTS: Of the 326 patients included, 65% underwent inhalation induction and 35% intravenous induction. The global LUS score was significantly higher in the inhalation group (12.0 vs. 4.0, p < 0.001). After propensity score matching (for age, presence of upper respiratory tract infection, duration of induction, and PEEP levels at induction), average treatment effect (ATE) of mask induction was 5.89 (95% CI, 3.21-8.58; p < 0.001) point on LUS global score and a coefficient of 0.35 (OR 1.41) for atelectasis. DISCUSSION: Inhalation induction is associated with a higher incidence of atelectasis in pediatric patients also when we adjusted for clinically relevant covariates. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT06069414.

Neonatal Sepsis: Aetiology, Pathophysiology, Diagnostic Advances and Management Strategies.

Neonatal sepsis, a bloodstream infection in the first 28 days of life, is a leading cause of morbidity and mortality among infants in both developing and developed countries. Additionally, sepsis is distinguished in neonates by unique pathophysiological and presentational factors relating to its development in immature neonatal immune systems. This review focuses on the current understanding of the mechanics and implications of neonatal sepsis, providing a comprehensive overview of the epidemiology, aetiology, pathophysiology, major risk factors, signs and symptoms and recent consensus on the diagnosis and management of both early-onset and late-onset neonatal sepsis. It also includes a discussion on novel biomarkers and upcoming treatment strategies for the condition as well as the potential of COVID-19 infection to progress to sepsis in infants.

Efficacy and Safety of Intravenous Diltiazem Versus Metoprolol in the Management of Atrial Fibrillation with Rapid Ventricular Response in the Emergency Department: A Comprehensive Umbrella Review of Systematic Reviews and Meta-analyses.

Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting 2.7-6.1 million people. AF can cause symptoms, but when it triggers a rapid ventricular response (RVR), most patients suffer from decompensation. Therefore, we performed an umbrella review of systematic reviews and meta-analyses comparing intravenous (IV) metoprolol and diltiazem to identify discrepancies, fill in knowledge gaps, and develop standardized decision-making guidelines for physicians to manage AF with RVR. A comprehensive search was conducted in PubMed, the Cochrane Library, and Scopus to identify studies for this umbrella review. The overall certainty of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation method, while the quality of the included reviews was evaluated using AMSTAR 2, the Cochrane Collaboration tool, and the Newcastle-Ottawa scale. This study comprehensively analyzed four meta-analyses covering 11 randomized controlled trials and 19 observational studies. The analysis showed that IV diltiazem treatment was significantly more successful in rate control for AF with rapid ventricular response (RVR) than IV metoprolol (risk ratio [RR], 1.30; 95% confidence interval [CI], 1.09-1.56; I 2 = 0%; P = .003). IV diltiazem also led to a significantly greater reduction in ventricular rate (mean difference, -14.55; 95% CI, -16.93 to -12.16; I 2 = 72%; P < .00001), particularly at 10 min. The analysis also revealed a significantly increased risk of hypotension associated with treatment with IV diltiazem (RR, 1.43; 95% CI, 1.14-1.79; I 2 = 0%; P = .002). In conclusion, IV diltiazem therapy achieved better rate control and ventricular rate decrease than metoprolol therapy in AF with RVR. Future clinical trials should compare calcium channel blockers and ß-blockers for heart rate control efficacy and safety, considering adverse events.

Outcome of intravenous thrombolysis in acute ischemic stroke patients with small vessel disease.

INTRODUCTION: Lacunar stroke (LS) subtype accounts for a quarter of ischemic strokes. Intravenous thrombolysis (IVT) is known to improve overall stroke outcomes. Very few studies have focused on the outcome of IVT in lacunar strokes. AIM: To detect the outcome of IVT in LS patients compared to non-thrombolysed LS patients. METHODS: Fifty patients presenting with LS received the standard protocol of IVT (Group I). They were compared to fifty matched LS patients who presented beyond the time window and were selected as the control group (Group II). Clinical outcome was measured using NIHSS within 24 h, NIHSS at discharge, and MRS after 3 months. Risk factors that could have affected clinical outcomes were compared in the thrombolysis group. RESULTS: The short-term clinical outcome of Group I showed statistically significant improvement of NIHSS after 24 hrs compared to Group II (mean NIHSS = 5.52±3.89 and 7.44±1.82 respectively), as well as on discharge (mean NIHSS = 3.88±3.50 and 5.78±2.97) respectively. For long-term outcomes, 94 % of GroupⅠ reached MRS 0, 1, and 2 (n = 47/50) versus 74 % (n = 36/50) in Group II. Longer door-to-needle time, severe WMCs (Fazekas score), and pneumonia were shown to be significant predictor factors for the worst outcome. CONCLUSION: IVT has improved short- and long-term outcomes in LS patients. Longer door-to-needle time, severe WMCs, and pneumonia were shown to be significant predictor factors for the worst outcome.

Fatal neonatal varicella infection despite intravenous immunoglobulin at birth.

There is a high risk of severe varicella infection in the neonate when the mother develops a rash around the time of delivery. Current guidelines recommend separation of mother-baby dyad and passive immunization to prevent severe infection in such cases. We report a case of severe varicella in a neonate whose mother developed primary varicella infection two days prior to delivery. The neonate had a fatal outcome despite physical separation from mother and passive immunization in the immediate postnatal period.

A review of intravenous immunoglobulin in the treatment of neuroimmune conditions, acute COVID-19 infection, and post-acute sequelae of COVID-19 Syndrome.

Intravenous immunoglobulin (IVIG) is an immunomodulatory therapy that has been studied in several neuroimmune conditions, such as Guillain-Barré Syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and multiple sclerosis. It has also been proposed as a potential treatment option for acute COVID-19 infection and post-acute sequelae of SARS-CoV-2 infection (PASC). IVIG is thought to function by providing the recipient with a pool of antibodies, which can, in turn, modulate immune responses through multiple mechanisms including neutralization of cytokines and autoantibodies, saturation of neonatal fragment crystallizable receptors, inhibition of complement activation, and regulation of T and B cell mediated inflammation. In acute COVID-19, studies have shown that early administration of IVIG and plasmapheresis in severe cases can reduce the need for mechanical ventilation, shorten ICU and hospital stays, and lower mortality. Similarly, in PASC, while research is still in early stages, IVIG has been shown to alleviate persistent symptoms in small patient cohorts. Furthermore, IVIG has shown benefits in another condition which has symptomatic overlap with PASC, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), though studies have yielded mixed results. It is important to note that IVIG can be associated with several potential adverse effects, such as anaphylaxis, headaches, thrombosis, liver enzyme elevations and renal complications. In addition, the high cost of IVIG can be a deterrent for payers and patients. This review provides a comprehensive update on the use of IVIG in multiple neuroimmune conditions, ME/CFS, acute COVID-19, and PASC, as well as covers its history, production, pricing, and mechanisms of action. We also identify key areas of future research, including the need to optimize the use of Ig product dosing, timing, and patient selection across conditions, particularly in the context of COVID-19 and PASC.