Intravenous Group Research Articles

Development of puerarin-loaded poly(lactic acid) microspheres for sustained ocular delivery: In vitro/vivo evaluation

Diabetic retinopathy, an ocular complication of diabetes, is an important cause of blindness in adults. Puerarin is considered to have promising potential for clinical use in treating diabetic retinopathy. In this study, we designed a novel puerarin-loaded poly(lactic acid) sustained-release microspheres suitable for ocular administration, and we assessed itsin vitro and in vivo properties. The preparation of puerarin-loaded microspheres was optimized by Box-Behnken response surface design. The encapsulation efficiency and drug loading of microspheres were 35.71% and 3.85%, respectively. The microspheres exhibited good dispersion and high safety, making it suitable for ocular drug delivery. In vitro release demonstrated that microspheres had a well-sustained release effectiveness, and its release behavior complied with the zero-order kinetic characteristics. The results of ocular tissue distribution revealed that the CmaxandAUC0-∞ of the microspheres group in the retina and choroid were considerably higher than those of the solution group and the intravenous injection group. This research revealed that intravitreal injection of microspheres can significantly prolong the half-life of puerarin in eye tissues and achieve sustained drug release. Therefore, intravitreal injection of microspheres has positive implications for the treatment of diabetic retinopathy.

Clinical efficacy of Endostar continuous infusion combined with concurrent chemoradiotherapy in the treatment of oesophageal squamous cell carcinoma

ObjectiveTo evaluate the effectiveness and safety of concurrent chemoradiotherapy using Endostar continuous infusion for treating oesophageal squamous cell carcinoma (OSCC).MethodA total of 62 patients with oesophageal carcinoma were divided into three groups: the Endostar continuous infusion group (n = 27), the Endostar intravenous drip group (n = 21) and the concurrent chemoradiotherapy group (n = 14). All patients underwent oesophageal radiotherapy (56–60 Gy) alongside concurrent chemotherapy (4 mg of raltitrexed +100 mg of oxaliplatin, two cycles). In the Endostar continuous infusion group, 210 mg of Endostar was administered via infusion once every 3 weeks for 72 h, repeated for two cycles. The Endostar intravenous drip group received a dosage of 15 mg/day of Endostar, administered once daily for 14 days, repeated for two cycles. The objective response rate (ORR) (complete remission + partial remission), progression-free survival (PFS), 2-year overall survival (2y-OS) and adverse reactions were observed.ResultsIn the Endostar continuous infusion, intravenous drip and concurrent chemoradiotherapy groups, the ORR was 100, 95.2 and 78.6%, respectively (p < 0.05). There was a statistically significant difference between the continuous infusion and concurrent chemoradiotherapy groups (p < 0.05). However, there was no statistically significant difference between the continuous infusion and intravenous drip groups or the intravenous drip and concurrent chemoradiotherapy groups (p > 0.05). The continuous infusion and intravenous drip groups had higher PFS rates than the concurrent chemoradiotherapy group (p < 0.05). Regarding the 2y-OS rate, no statistically significant difference was observed among the three groups (p > 0.05). Furthermore, there was no statistically significant difference in adverse reactions among the groups (p > 0.05).ConclusionConcurrent chemotherapy based on endostatin is effective and safe in the treatment of OSCC. Continuous 3-day Endostar infusion treatment can significantly enhance both short-and long-term therapy efficacy in patients while maintaining a high level of safety.

Comparison of ketorolac intravenous versus acetaminophen intravenous in treating headache following head trauma: a semi-experimental study

BackgroundPost-traumatic headache is a disabling secondary headache disorder often attributed to traumatic brain injury and affects millions of individuals worldwide. Few studies have been done on the treatment needs of these patients in emergency departments. The purpose was to compare the effectiveness of ketorolac intravenous versus acetaminophen intravenous in reducing headaches in patients following head trauma.MethodsThis was a semi-experimental study in which the participants were assigned two groups. In the acetaminophen intravenous group, 1 g acetaminophen and in the ketorolac intravenous group, 60 mg of this drug was injected. Statistical analysis was done with IBM SPSS statistical software version 21, and a P-value less than 0.05 was considered statistically significant.ResultsAmong samples after 6 h from the injection, the pain score in the ketorolac intravenous group was less than the acetaminophen intravenous group (P = 0.006). Also, the pain reduction rate in the ketorolac intravenous group was more than the acetaminophen intravenous group from before the injection until 2 h after it (P = 0.01) and before injection until 6 h after it (P = 0.001). The frequency of drowsiness in 2 and 6 h after drug administration in the ketorolac intravenous group was lower than the acetaminophen intravenous group, which is significant in 2 h after drug administration (P = 0.038). The verbal analog scale score comparison for two groups 2 h before medicine administration with pain control score (P = 0.03) and 6 h with pethidine use control (P = 0.003) is significant.ConclusionsAccording to this study, ketorolac’s intravenous effect on pain control is better than that of acetaminophen intravenous. With more samples, we can express the survey results more decisively in the future.

Intravenous versus oral tranexamic acid in elderly transforaminal lumbar interbody fusion patients: A prospective cohort study

BackgroundTranexamic acid (TXA) can effectively reduce intraoperative blood loss and transfusion rates. However, in spinal surgery, the number of surgical levels can significantly influence intraoperative and postoperative bleeding, particularly among the elderly, contributing to the persistently high rate of transfusion during the perioperative period. To verify the safety and efficacy of different application methods of TXA in elderly patients undergoing transforaminal lumbar interbody fusion (TLIF), a prospective cohort study was conducted. MethodsA total of 958 patients undergoing TLIF were randomly assigned to receive 2 g of oral TXA two hours before surgery or 15 mg/kg of intravenous TXA 30 min before surgery, or to a control group. The samples were further divided into three categories based on the number of fused segments (one-level fusion, two-level fusion, and three-level fusion). The primary outcomes were the total blood loss and transfusion rate. Secondary outcomes included intraoperative blood loss, postoperative blood loss, drainage volume, time until drain removal, perioperative transfusion volume, length of stay, thrombotic events, and other adverse events. Results336 patients received intravenous TXA and 314 patients were received oral TXA. Patient demographic factors were similar between groups. In the one-level fusion surgery cohort, comparisons across the three groups revealed no statistically significant disparities in total blood loss, transfusion rates, or drainage volumes (P > 0.05). In both two-level and three-level fusion surgeries, patients administered with TXA experienced a notably reduced perioperative bleeding compared to the control group (P < 0.01). Interestingly, a significant disparity was observed in the drainage volumes between the intravenous and oral administration groups (P = 0.026), specifically within the context of two and three-level fusion procedures. ConclusionIn elderly patients undergoing TLIF surgery, both intravenous and oral administrations of TXA are safe and effective. Oral TXA, being more economical and non-invasive compared to intravenous injection, holds promise for clinical use.

Effect of intravenous versus inhaled anesthetics on blood-brain barrier dysfunction and neuroinflammation in elderly patients undergoing major surgery: study protocol of a randomized controlled trial

BackgroundPostoperative cognitive dysfunction (POCD) is one of the major complications after surgery, with devastating clinical outcomes. Although POCD is a condition with a multifactorial pathophysiology, blood-brain barrier (BBB) dysfunction and neuronal injury have been shown to play a critical role, especially in the elderly. Previous studies have demonstrated that the choice of anesthetics affect BBB permeability and neuroinflammation. However, most studies are carried out on animals, with limited research undertaken on humans. Therefore, we will compare the effect of intravenous anesthetics and inhaled anesthetics on BBB dysfunction and the change of inflammatory markers after surgery.MethodsOne hundred and fifty-four patients who are 60 years of age or older undergoing major surgery for more than 2 h will be randomly allocated to two anesthetics groups (intravenous, inhaled) in a 1:1 ratio. In the intravenous anesthetics group (group P), propofol will be infused with a target-controlled infusion (TCI) system throughout the entire surgery. In the inhaled anesthetics group (group G), bolus injection of propofol will be administered for loss of consciousness, and simultaneously sevoflurane will be initiated for the maintenance of anesthesia. The primary outcome is the change in serum S100 calcium binding protein β (S100β) at four time points: before induction of anesthesia, at the end of surgery, 4 h after surgery, postoperative day 1. Secondary outcomes include changes in the inflammatory markers, serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and C-reactive protein; the incidence of delirium; and the change in the cognitive function between groups. In patients pre-scheduled for postoperative intensive care unit admission, the cerebrospinal fluid/serum albumin quotient (Qalb) between the two groups will be compared before and after surgery, and change in inflammatory markers in serum and CSF will be analyzed in relation to the Qalb.DiscussionThe current study will compare the effect of intravenous versus inhaled anesthetics on blood-brain barrier permeability and, as a result, the difference in neuroinflammation in elderly patients. Also, the study results will provide additional information to develop intraoperative anesthetic strategies to reduce POCD.Trial registrationThe trial was prospectively registered at Clinical Trials protocol registration with identifier 2310-117-126 on April 9, 2024.

Postoperative recovery in peroral versus intravenous antibiotic treatment following laparoscopic appendectomy for complicated appendicitis: a substudy of a cluster randomized cluster crossover non-inferiority study.

Acute appendicitis is the most common cause of abdominal pain requiring surgery, usually managed with laparoscopic appendectomy. In Denmark, the standard postoperative treatment for complicated cases involves intravenous antibiotics. This study compares peroral versus intravenous antibiotics in the context of fast-track surgery and Enhanced Recovery After Surgery (ERAS) protocols. Our objective is to evaluate the impact of peroral versus intravenous antibiotics on patient-reported outcomes following laparoscopic appendectomy for complicated appendicitis. This was a sub-study within a broader Danish cluster-randomized non-inferiority trial conducted at Zealand University Hospital, focusing on adult patients undergoing laparoscopic appendectomy for complicated appendicitis. Participants were randomized into two groups: one receiving a three-day course of peroral antibiotics and the other intravenous antibiotics after surgery. Recovery quality was assessed on the third postoperative day using the Quality of Recovery-15 (QoR-15) questionnaire. The study included 54 patients, 23 in the peroral and 31 in the intravenous groups. The peroral group reported significantly better recovery outcomes, with higher QoR-15 scores (mean difference of 12 points, p < 0.001). They also experienced shorter hospital stays, averaging 47 h less than the intravenous group (p < 0.001). No significant differences between the groups were observed in readmissions or severe postoperative complications. Peroral antibiotic administration after laparoscopic appendectomy for complicated appendicitis significantly improves patient recovery and reduces hospital stay compared to intravenous antibiotics. These results advocate a potential shift towards peroral antibiotic use in postoperative care, aligning with ERAS principles. ClinicalTrials.gov NCT04803422.

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

IntroductionAtelectasis 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).MethodsThis 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.ResultsOf 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.DiscussionInhalation induction is associated with a higher incidence of atelectasis in pediatric patients also when we adjusted for clinically relevant covariates.Trial registrationClinicalTrials.gov identifier: NCT06069414.

Comparison of Total Intravenous Anesthesia with Inhaler Anesthesia in Children Intubated with Remifentanil without Muscle Relaxant

Objective: The effects of remifentanil and muscle relaxant-free intubation as well as total intravenous anesthesia and inhaled anesthesia for tonsillectomy and/or adenoidectomy in children were compared. Materials and Methods: The study was conducted on 80 patients who were to undergo tonsillectomy and/or adenoidectomy between December 2014 and June 2015. Patients were randomized and divided into two groups. In the total intravenous anaesthesia group, 2.5 mg/kg propofol and 2 mcg/kg remifentanil were administered as induction within 90 seconds. In this group, 3 mg/kg/h propofol and 0.5 mcg/kg/min remifentanil were used for maintenance of anesthesia. In the sevoflurane group, 8% sevoflurane and 2 mcg/kg remifentanil were administered as induction within 90 seconds. In this group, 2.5% sevoflurane, 50% nitrogen protoxide and 50% oxygen were used at 6 l/min for maintenance of anesthesia. Results: Peak heart rate and systolic arterial pressure were significantly higher in Group I. Diastolic arterial pressure was significantly higher in Group T at 1 and 2 minutes after intubation and in Group 2 at 10 minutes postoperatively. Mean arterial pressure was higher in Group T at 2 minutes after intubation. In addition, Wong-Baker pain scale and agitation score were significantly higher in Group I. Spontaneous respiration and extubation time were significantly shorter in Group I. There was no difference between the groups in terms of side effects. Conclusion: Group total intravenous anaesthesia was thought to be a better choice in children because it had less impact on postoperative pain, agitation and recovery.

Intravenous versus oral iron for anaemia among pregnant women in Nigeria (IVON): an open-label, randomised controlled trial

Oral iron for anaemia in pregnancy is often not well tolerated, with poor adherence. Iron administered intravenously might address these tolerance and adherence issues. We investigated the effectiveness and safety of intravenous ferric carboxymaltose versus oral ferrous sulphate on anaemia and iron deficiency among pregnant women in Nigeria. We did a multicentre, open-label, parallel, randomised controlled trial of pregnant women (aged 15-49 years) with haemoglobin (Hb) concentrations of less than 10 g/dL at 20-32 weeks' gestation from 11 primary, secondary, or tertiary health facilities in Nigeria (five in Lagos and six in Kano). Exclusion criteria included vaginal bleeding, blood transfusion or major surgery within the past 3 months, symptomatic anaemia, anaemia known to be unrelated to iron deficiency, clinically confirmed malabsorption syndrome, previous hypersensitivity to any form of iron, pre-existing maternal depression or other major psychiatric illness, immune-related diseases, such as systemic lupus erythematosus or rheumatoid arthritis, or severe allergic reactions. Participants were randomly assigned (1:1) by nurses and doctors using a web-based randomisation service to either receive a single dose of intravenous ferric carboxymaltose (20 mg/kg to a maximum of 1000 mg) or oral ferrous sulphate (200 mg; 65 mg elemental iron) three times daily until 6 weeks postpartum. The study was primarily unmasked. Primary outcomes were maternal anaemia (Hb <11 g/dL) at 36 weeks' gestation and preterm birth at before 37 weeks' gestation, with analysis by intention to treat in participants with available data. This study was registered at the ISRCTN registry on Dec 10, 2020 (ISRCTN63484804) and on ClinicalTrials.gov (NCT04976179) on April 7, 2021. Between Aug 10, 2021, and Dec 15, 2022, 13 724 pregnant women were screened for eligibility. 12 668 were excluded due to ineligibility for inclusion, and 1056 provided consent to participate and were randomly assigned to either the intravenous or oral administration groups. 527 were assigned to the intravenous ferric carboxymaltose group and 529 were assigned to the oral ferrous sulphate group. 518 in the intravenous group were assessed at 36 weeks' gestational age and after 518 deliveries, and 511 completed the 6 weeks postpartum visit. 513 in the oral ferrous sulphate group were assessed at 36 weeks' gestational age and after 512 deliveries, and 501 completed the 6 weeks postpartum visit. No significant difference was found in anaemia at 36 weeks (299 [58%] of 517 in the intravenous group vs 305 [61%] of 503 in the oral group; risk ratio 0·95, 95% CI 0·85-1·06; p=0·36), nor in preterm birth (73 [14%] of 518 vs 77 [15%] of 513; 0·94, 0·70-1·26; p=0·66). There were no significant differences in adverse events. The most common adverse events were diarrhoea (in six participants) and vomiting (in three participants) in the oral group and fatigue (in two participants) and headache (in two participants) in the intravenous group. Although the effect on overall anaemia did not differ, intravenous iron reduced the prevalence of iron deficiency to a greater extent than oral iron and was considered to be safe. We recommend that intravenous iron be considered for anaemic pregnant women in Nigeria and similar settings. Bill & Melinda Gates Foundation.

Comparison of inhalational and intravenous anesthesia induction on electroencephalogram and cerebral perfusion in children with congenital heart disease: A secondary analysis of a randomized controlled trial

ObjectiveThe effects of anesthetics on electroencephalograms and cerebral perfusion remain understudied in children with congenital heart disease. With regard to this, we compared inhalational anesthesia induction and intravenous anesthesia induction. DesignA randomized controlled trial. SettingOperation room in two tertiary hospitals. ParticipantsA cohort of 116 pediatrics patients undergoing cardiac surgery. Measurements and main resultsThe patients were randomly assigned to either the intravenous group (n=58) or the inhalational group (n=58). The inhalational group received anesthesia induction with 4-6% sevoflurane and a bolus of pipecuronium 0.2 mg/kg, while the intravenous group received anesthesia induction with intravenous midazolam 0.2 mg/kg, pipecuronium 0.2 mg/kg, and sufentanil 1 μg/kg. Ten minutes after tracheal intubation, the following parameters were measured: spectral edge frequency, burst suppression event, patient state index, middle cerebral artery blood flow velocity, cerebral oxygen saturation, and hemodynamic parameters. In comparison to the intravenous group, the inhalational group exhibited significant increases in 95% spectral edge frequency, ratio of burst suppression event, blood flow velocity in the middle cerebral artery, and cerebral oxygen saturation (P<0.05 for all), as well as decreases in systolic pressure, diastolic pressure, cardiac index, and the maximal slope of systolic upstroke (P<0.05 for all). ConclusionThe administration of sevoflurane for anesthesia induction results in more burst suppression, while also demonstrating superior cerebral perfusion when compared to the use of intravenous medications for anesthesia induction.

Efficacy and safety of oral versus intravenous cyclophosphamide in treatment of connective tissue disease-related interstitial lung disease.

Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.

Effect of subcutaneous vs. intravenous tocilizumab in patients with severe COVID-19: a systematic review.

To systematically evaluate the efficacy of subcutaneous tocilizumab in the treatment of patients with severe COVID-19 and provide evidence for the rational use of subcutaneous tocilizumab in patients with severe COVID-19. This meta-analysis was carried out in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. We searched the Cochrane Library, PubMed, Embase, CNKI, SinoMed, and Wanfang Medical Network electronic databases up to 11 January 2023 to identify relevant studies. To obtain the most recent clinical studies of subcutaneous injection of tocilizumab for the treatment of patients with severe COVID-19, we also searched the preprint platforms medRxiv and ChinaXiv. Furthermore, we searched ClinicalTrials.gov for relevant unpublished studies. The studies were screened based on the PICOS principle. The included studies were classified and evaluated for quality based on research type. The RevMan 5.3 software was used to conduct the meta-analysis, and a descriptive analysis was performed to examine relevant outcome indicators. Five observational studies were obtained, involving a total of 498 patients (240 patients in the subcutaneous injection group and 258 patients in the intravenous injection group). All of the studies were of the highest quality. The meta-analysis of the included studies revealed that the mortality rate of patients who received subcutaneous tocilizumab to treat COVID-19 was not significantly higher than that of the intravenous injection group [23.3% (45/193) vs. 18.4% (39/212), RD = 0.06, 95% CI = - 0.01 ~ 0.13, P = 0.11]. Furthermore, there was no significant difference in the proportion of patients requiring mechanical ventilation between the two groups [24.5% (35/143) vs. 22% (35/159), RD = 0.03, 95% CI = - 0.07 ~ 0.12, P = 0.56]. The meta-analyses do not provide evidence that subcutaneous and intravenous tocilizumab formulations for the treatment of severe COVID-19 infection differ regarding their effectiveness. Considering that the meta-analyses cannot replace an appropriately powered non-inferiority study, subcutaneous formulations still need to be used with caution and only when intravenous formulations are in short supply. At present, there is a lack of randomized controlled trials of subcutaneous injection of tocilizumab for the treatment of severe COVID-19, and more clinical research should be conducted.

Intragallbladder versus intravenous indocyanine green (ICG) injection for enhanced bile duct visualization by fluorescent cholangiography during laparoscopic cholecystectomy: a retrospective cohort study.

Iatrogenic bile duct injuries (BDIs) prevention during laparoscopic cholecystectomy (LC) relies on meticulous anatomical dissections through direct visualization. Near-infrared fluorescence (NIRF) with indocyanine green (ICG) improves the visualization of extrahepatic biliary structures. Although ICG can be administered either intravenously or intragallbladder, there remains uncertainty regarding the optimal method for different patient populations. This study sought to assess the suitability of each method for specific patient groups. Between October 2021 and May 2022, 59 consecutive patients underwent fluorescence-guided LC at West China Hospital of Sichuan University. Among them, 32 patients received an intravenous injection of ICG (10 mg) 10 to 12 hours prior to surgery (Group A: the intravenous group), while 27 patients received an intragallbladder injection of ICG (10 mg) (Group B: the intragallbladder group). Baseline clinical factors, inclusion criteria, and measurements of parameters and complications were assessed. Data were retrospectively collected and analyzed to evaluate the comparability of the two groups and the clinical outcomes. Groups A and B included 32 patients (18 males, 14 females), and 27 patients (13 men, 14 women), respectively. In our statistical analysis, significant differences were observed in preoperative diagnoses between the two groups (P=0.041), but the majority of other baseline clinical factors were comparable. Notably, no statistically significant differences were found in complication rates. However, Group A had a shorter operative time (60.38±9.35 vs. 66.78±9.88 min, P=0.01) and superior bile duct fluorescence (P=0.04) than Group B. Interestingly, fluorescence was not observed in impacted gallbladder stones in Group B. Additionally, patients with cirrhosis (P=0.008) and fatty liver (P=0.005) in Group B had higher common bile duct-to-liver ratios (BLRs) than those in Group A. ICG fluorescence cholangiography allows to visualize extrahepatic biliary anatomical structures with both administration methods. However, the efficacy of bile duct fluorescence varies with different administration routes in diverse patient populations. Hence, appropriate administration route selection for ICG should be tailored to individual patients.

Infection route influence the consequences of Nocardia farcinica infection in BALB/c mice

BackgroundNocardia, a rare but potentially fatal pathogen, can induce systemic infections with diverse manifestations. This study aimed to investigate the tissue and organ damage caused by Nocardia farcinica (N. farcinica) in mice via different infection routes, evaluate the resulting host immune responses, and assess its invasiveness in brain tissue.MethodsBALB/c mice were infected with N. farcinica through intranasal, intraperitoneal, and intravenous routes (doses: 1 × 10^8, 1 × 10^7, 1 × 10^7 CFU in 50 µl PBS). Over a 7-day period, body temperature, weight, and mortality were monitored, and samples were collected for histopathological analysis and bacterial load assessment. Serum was isolated for cytokine detection via ELISA. For RNA-seq analysis, mice were infected with 1 × 107 CFU through three infection routes, after which brain tissue was harvested.ResultsIntraperitoneal and intravenous N. farcinica infections caused significant clinical symptoms, mortality, and neural disruption in mice, resulting in severe systemic infection. Conversely, intranasal infection primarily affected the lungs without causing significant damage to other organs. Intraperitoneal and intravenous infections significantly increased serum cytokines, particularly TNF-α and IFN-γ. RNA-seq analysis of brains from intravenously infected mice revealed significant differential gene expression, whereas the intranasal and intraperitoneal routes showed limited differences (only three genes). The enriched Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in the intravenous group were primarily related to immune processes.ConclusionThe study demonstrated that intravenous N. farcinica infection induces significant clinical symptoms, triggers an inflammatory response, damages multiple organs, and leads to systemic infections.

Enteral Nutrition in Neonates on Inotropic Support Admitted to a Tertiary Neonatal Intensive Care Unit: A Prospective Cohort Study.

Background Early initiation of enteral feeding in neonates on inotropic support may improve clinical outcomes compared to intravenous fluids, but the safety and optimal inotrope levels for enteral nutrition remain unclear. This study aims to assess the early initiation of enteral feeding versus intravenous fluids in newborns on inotrope support andto compare the clinical outcome in terms of hospital stay, morbidity, and mortalityin neonates with enteral feed versus intravenous (IV) fluid group on inotropes. It also focuses on evaluating the safety of enteral nutrition in neonates with inotropic support and determining the cutoff levels of the inotropes at which enteral feed is well tolerated. Methodology A prospective cohort study was conducted at a tertiary care center in northern Karnataka from June 2022 to December 2023. Neonates born after 28 weeks or more of gestation or weighing more than 1000 grams with fluid nonresponsive shock were enrolled for the study. Neonates with gastrointestinal comorbidities or birth weight below 1000 grams, younger than 28 weeks of gestation, and with lethal congenital malformations were excluded. Eligible neonates were enrolled by the investigator into enteral and intravenous fluid groups at the clinical discretion of the treating neonatologist. Enteral feeding commenced with expressed breast milk or milk from milk bankafter 6 hours of stable circulation while the intravenous fluid group received no feed initially. Inotropes were tapered upon stable circulation with feed volumes adjusted based on tolerance. The data obtained was entered into a Microsoft Excel sheetand statistical analyses were performed using IBM SPSS Statistics software, version 20. The results were presented as mean, standard deviation counts, percentagesand diagrams. For normally distributed continuous variables between the two groups, they were compared using an independent sample t-test. For not normally distributed variables, the Mann-Whitney U test was used. Categorical variables between the two groups were compared using the chi-square test and Fisher's exact test and p<0.05 was considered statistically significant. Results The study included 142 neonates (71 per group). The enteral nutrition grouphad a higher percentage (62; 87.32%) of improved and discharged neonates than the intravenous fluid group(56; 78.87%).The mean time to reach full feeds was significantly lower in the enteral nutrition group (6.04 days) as compared to the intravenous fluid group (9.78 days), with a p-value of < 0.0001. Similarly, the duration of neonatal intensive care unit (NICU) stay was significantly shorter for enteral nutrition group (7.38 days) compared to intravenous fluid group (11.37 days), also with a p-value of < 0.0001. Three patients (4.22%) chose to get discharged against medical advice in the enteral nutrition group while five patients (7.04%) did the same in the intravenous fluid group. The death rate was also higher among intravenous fluid group (10; 10.08%) compared to enteral nutrition group (6; 8.45%).Independent samples t-test showed significant differences in time to reach full feed and duration of NICU stay between cases and controls. Conclusion Neonates receiving enteral feeds had significantly shorter NICU stays, suggesting improved clinical management. Adrenaline (0.1 mcg/kg) with dobutamine (10 mcg/kg) emerged as the optimal inotrope combination for feed tolerance.

Oral versus intravenous antibiotic therapy for Staphylococcus aureus bacteremia or endocarditis: a systematic review and meta-analysis of randomized controlled trials.

We conducted a systematic review of randomized controlled trials (RCTs) to generate more precise estimates of the efficacy and safety of oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis. MEDLINE, EMBASE, the Cochrane Library, and Web of Science database were searched through February 21st, 2024. RCTs were included if they compared oral versus intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, and appropriately reported outcomes for each group. Risk of bias was assessed using the revised Cochrane tool for assessing risk of bias in randomized trials. Heterogeneity between studies was evaluated with the Cochran's Q-statistic and I2 test. Treatment effects were summarized with pooled risk ratios using a random effects model meta-analysis. (PROSPERO CRD42024481512). Only four RCTs met criteria for inclusion in meta-analysis. Among participants assessed for treatment failure, there was no difference between the oral and intravenous therapy groups (RR 0.99; 95% CI, 0.63-1.57; I2 = 0%). There was also no significant difference in adverse events between oral and intravenous therapy groups (RR 0.65; 95% CI, 0.07-5.94; I2 = 74%); however, the confidence interval is wide, and heterogeneity was high. In this systematic review of RCTs comparing oral to intravenous antibiotic therapy for S. aureus bacteremia or endocarditis, few studies met eligibility criteria for inclusion. Meta-analysis of these studies suggests that transitioning from intravenous to oral therapy is likely effective in a subgroup of carefully selected patients. Additional randomized trials are necessary before transition to oral therapy can be routinely recommended.

COMPARISON OF TOPICAL AND INTRAVENOUS LIGNOCAINE IN PATIENTS UNDERGOING LARYNGEAL MASK AIRWAY INSERTION UNDER PROPOFOL: A RANDOMIZED CONTROLLED TRIAL

Laryngeal mask airway (LMA) insertion is a common technique used in general anesthesia, but it may induce airway reflexes such as coughing, gagging, and laryngospasm. Lignocaine, whether administered topically or intravenously, is often used to suppress these reflexes. However, the comparative efficacy of these two routes remains unclear. Objective: This study aims to compare the effectiveness of topical versus intravenous lignocaine in facilitating LMA insertion and minimizing airway complications in patients undergoing propofol anesthesia. Methods: A randomized controlled trial was conducted on 62 patients undergoing elective surgeries under general anesthesia at a tertiary care hospital. Patients were randomly assigned into two groups: Group A (n = 31) received 40 mg of topical lignocaine aerosol, while Group B (n = 31) received intravenous lignocaine 1.5 mg/kg. Both groups were induced with propofol (2 mg/kg) prior to LMA insertion. Primary outcomes included the number of LMA insertion attempts, airway responses (coughing, gagging, laryngospasm), and hemodynamic parameters (systolic blood pressure, diastolic blood pressure, and heart rate) recorded at baseline and 1, 2, and 3 minutes post-insertion. Results: LMA insertion on the first attempt was successful in 93.5% of patients in the topical lignocaine group compared to 74.2% in the intravenous group (p = 0.03). Airway reflexes were significantly lower in the topical group, with coughing, gagging, and laryngospasm rates of 6.5%, 16.1%, and 9.7%, respectively, compared to 32.3%, 45.2%, and 29.0% in the intravenous group (p &lt; 0.05). Hemodynamic parameters, including systolic and diastolic blood pressure and heart rate, showed no significant differences between the two groups at baseline or post-insertion. Conclusion: Topical lignocaine significantly improves conditions for LMA insertion compared to intravenous lignocaine, resulting in fewer airway complications while maintaining similar hemodynamic stability. Therefore, topical lignocaine is recommended for optimizing LMA insertion during propofol anesthesia.

Phase 1 Trials of Gatralimab, a Next-Generation Humanized Anti-CD52 Monoclonal Antibody, in Participants with Progressive Multiple Sclerosis.

Lymphocyte depletion via anti-CD52 monoclonal antibody (mAb) therapy is an effective treatment strategy for relapsing-remitting multiple sclerosis (MS) but is associated with infusion/injection-associated reactions (IARs) and autoimmune-related adverse events (AEs). Gatralimab is a next-generation humanized anti-CD52 mAb. Two first-in-human trials were conducted in participants with progressive MS to assess the pharmacodynamics, pharmacokinetics, and safety of gatralimab administered via subcutaneous (SC) and intravenous (IV) routes, and to determine the effect of different comedication regimes on IARs to SC gatralimab. A Phase 1 trial (NCT02282826) included double-blind, placebo-controlled sequential ascending single IV (1, 3.5, and 12mg) and SC (12, 36, and 60mg) dose groups. A Phase 1b trial (NCT02977533) involved five groups who received SC gatralimab (36, 48, or 60mg) and different comedications. A long-term safety (LTS) study (NCT02313285) examined safety and pharmacodynamics over 4years. Gatralimab produced depletion of lymphocytes (dose-dependently) and CD4+ regulatory T cells, with partial repopulation to normal values by approximately 12months. Peak serum gatralimab concentrations followed dose-proportionality and were delayed by 6.0-7.5days following SC administration. Treatment-emergent AEs, including IARs, were reported for most participants but were generally of mild or moderate severity, and treatment-emergent serious AEs were mostly MS-related. Methylprednisolone and antihistamine comedications were associated with reduced incidence of fevers and skin and subcutaneous tissue AEs, respectively. During the LTS study, one participant (3.0%) experienced an autoimmune-related AE (Basedow's disease), and subsequently died from pulmonary sepsis deemed unrelated to gatralimab by the investigator. These data show that gatralimab achieves the desired pharmacodynamic effect of lymphocyte depletion followed by repopulation, and has an acceptable safety profile, including low risk of non-MS autoimmunity. Although gatralimab is no longer in development for MS, insights from these trials may inform the development of comedication regimes of future anti-CD52 mAbs and subcutaneous formulations of other lymphocyte-depleting mAbs. NCT02282826, NCT02977533, NCT02313285.

Endovascular Treatment With or Without Intravenous Thrombolysis for Acute Ischemic Stroke Due to Tandem Occlusion: A Systematic Review and Meta-Analysis.

Endovascular treatment (EVT) has been demonstrated to be effective for patients with tandem occlusion. The efficacy and safety of intravenous thrombolysis before EVT in patients with tandem occlusion remain debatable. We conducted a systematic review and meta-analysis with PubMed, EMBASE, and the Cochrane Library from inception to September 2023. The primary outcome was functional independence, defined as a modified Rankin Scale score of 0 to 2 at 90 days. The secondary outcomes included the successful recanalization rate, symptomatic intracerebral hemorrhage, and mortality at 90 days. In total, 9 studies with 1838 enrolled participants were identified. Our results showed that, compared with treatment with EVT alone, intravenous thrombolysis before EVT was associated with a greater proportion of functional independence at 90 days (odds ratio [OR], 1.39 [95% CI, 1.14-1.69]; P=0.001), a greater rate of successful recanalization (OR, 1.45 [95% CI, 1.11-1.89]; P=0.007) and decreased mortality (OR, 0.68 [95% CI, 0.50-0.93]; P=0.02). Furthermore, there was no significant difference in symptomatic intracerebral hemorrhage between the intravenous thrombolysis plus EVT group and the EVT alone group (OR, 1.16 [95% CI, 0.79-1.70]; P=0.45). In patients with acute ischemic stroke and tandem occlusion, intravenous thrombolysis before EVT was associated with a greater rate of favorable functional outcomes and successful recanalization and a lower mortality rate without an increased risk of symptomatic intracerebral hemorrhage compared with patients receiving EVT alone.

Comparison of Mean Postoperative Hemoglobin Concentrations in Patients Undergoing Total Knee Arthroplasty With Intravenous Versus Intraarticular Administration of Tranexamic Acid.

Total knee arthroplasty (TKA) may result in significant blood loss, but it is an effective and affordable treatment for severe osteoarthritis in the knees. While intravenous (IV) tranexamic acid(TXA) is a commonly used technique, intraarticular (IA) TXA has just recently started to gain traction in joint replacement procedures. The purpose of this research was to examine the mean postoperative hemoglobin concentration in order to assess the effectiveness of TXAadministered IVvs IAafter TKA. To assess the effectiveness of intraarticular TXA against intravenous administration. The six-month randomized controlled experiment was started from October 5, 2022, to April 4, 2023, at "the Orthopedics Department of Sir Ganga Ram Hospital in Lahore". The experiment included 60 patients undergoing TKA, ranging in age from 30 to 70. All members of the surgical team, including the supervisor (a consultant surgeon), assistants, and researchers, were present throughout the surgery. A high, thigh tourniquet was employed in every case, and a medial parapatellar technique was performed as well. Before the tourniquet was inflated, individuals in the intravenous group received 1 g of TXA intravenously 15-30 minutes beforehand. In the IA group, the "patient received an injection of 2 g of TXA in a 20 mL solution"straight into the joint after the prosthesis was implanted and secured. Data were analyzed using SPSS (version 26), with numerical data (age, BMI, surgical length, and hemoglobin levels) presented as mean ± SD and categorical factors (gender, American Society of Anesthesiologists (ASA) class, anatomical side) shown as frequency and percentage. The mean postoperative hemoglobin levels were compared between groups using an independent sample t-test, with data stratified by various factors and p ≤ 0.05 considered significant. There were 60 patients in this study, ranging in age from 30 to 70. The mean±SD age was 48.73±10.35 years. Patients' mean BMI was 25.51±4.48 kg/m², with representation across underweight, normal, overweight, and obese categories. The procedure took 173.10±32.61 minutes. The overall postoperative hemoglobin concentration was significantly higher in the IA TXA group (12.12±1.32 g/dL) compared to the IV TXA group (11.11±1.10 g/dL), with a p-value of 0.02. Additionally, when stratified by age, the IA TXA group consistently demonstrated higher postoperative hemoglobin levels across all age brackets, with significant differences observed in the 51-60 years (p = 0.001) and 61-70 years (p = 0.011) groups. Gender-based comparisons showed that IA TXA was associated with higher postoperative hemoglobin levels for both males (p < 0.05) and females (p < 0.05) compared to IV TXA. This study demonstrates that IAadministration of TXAis more effective in maintaining higher postoperative hemoglobin concentrations compared to IVTXA in patients undergoing TKA. The IA TXA group consistently achieved significantly higher hemoglobin levels across various age groups and both genders, indicating superior efficacy in reducing blood loss associated with TKA. These findings suggest that IA TXA could be a preferable alternative to IV TXA for enhancing postoperative hemoglobin recovery and potentially improving patient outcomes in knee arthroplasty procedures.