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Nine models were evaluated as candidate glomerular filtration rate (GFR) reference standards in three datasets using [51Cr(EDTA)]– or [169Yb(DTPA)]2− anions in 98 studies. Noncompartmental methods formed an upper limit for estimating mass excreted and voluntary urine collection formed a lower limit. For current models and methods, reduced GFR in adults resulted in inflated clearance estimates. Two different logarithmic models with exponential tails were created and may have underestimated reduced clearance. The logarithmic formulae can be used with only two plasma samples, and fit 13 multiple time-samples from 5 min to 24 h with an 8% standard deviation of residuals compared to 20% error for monoexponentials. For shorter times (4 or 5 h) the fit errors decreased but the ratio of errors remained at circa 2.5 times lesser for the logarithmic versus monoexponential models. Adaptively regularised gamma variate, Tk-GV, models that are well documented, but not in common use, were largely contained within the reference extreme values, were unbiased for different levels of clearance and were the only models to be uncorrelated to volume of distribution from mean residence time divided by weight. Using Tk-GV as a candidate reference standard, potentially better methods for routine clinical usage were discussed. Prospective clinical testing, and metabolic scaling of decreased renal function is advised for potential changes to patient triage. [ABSTRACT FROM AUTHOR]

Objective To explore the effect of preoperative intravenous administration of different doses of esketamine on sedation and anesthesia induction compliance in preschool children. Methods A total of 90 children scheduled for laparoscopic high ligation of hernia under general anesthesia were allocated, aged 1 to 6 years. The children were divided into the S1 group, the S2 group and the S3 group (according to different intravenous doses of esketamine 0.6 mg/kg, 0.8 mg/kg and 1.0 mg/kg respectively) by random number table method, with 30 patients in each group. The Ramsay sedation score of children were recorded before medication (T0), separating with parents 1 min after medication (T1) and anesthesia induction (T2). Induction Compliance Checklist (ICC) score and heart rate were also recorded. The adverse events during sedation and after recovery, and the recovery time were recorded. Results At T1 and T2, the Ramsay sedation score was better in the S2 group and the S3 group than that of the S1 group (P＜0.05), and the Ramsay score of the S3 group was higher than that of the S2 group at T2 (P＜0.05). The ICC score was lower in the S3 group than that of the S1 group and the S2 group (P＜0.05). There was no significant difference in ICC score between the S1 group and the S2 group (P＞0.05). There were significant differences in ICC grades between the three groups (P＜0.01). The proportion of children with perfect induction cooperation (ICC=0) was significantly higher in the S3 group than that in the S1 group and the S2 group, and the proportion of children with poor induction cooperation (ICC=4-10) was significantly lower in the S3 group than that in the S1 group and the S2 group (P＜ 0.05). There were no significant differences in the incidence of adverse events and recovery time between the three groups (P＞0.05). Conclusion Preoperative intravenous administration of esketamine 0.8 mg/kg and 1.0 mg/kg can improve the sedation effect of preschool children, but the sedation effect and induction compliance is superior with 1.0 mg/kg anesthesia induction. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether reducing the volume of intravenous iodinated contrast material injected during brain computed tomography (CT) provides reliable and accurate imaging without compromising diagnostic accuracy., Methods: This prospective study enrolled patients undergoing enhanced brain CT at a single tertiary hospital. Subjects who agreed to participate received a reduced dose of 60 ml contrast. The images were compared to an age and gender-matched control group who received the conventional 80 cc dose. Neuroradiologists assessed image quality and interpretation using a 5-point Likert scale with six specific domains. Based on ICC, inter-rater reliability was high at 0.873. Multiple linear regression predicted overall diagnostic accuracy based on contrast dose, age, and gender. Visual Grading Characteristics (VGC) analysis was also performed to quantify regional brain enhancement differences between the two contrast groups., Results: The study included 47 patients in the 60 cc group and 55 in the 80 cc control group. The results showed the 80 cc group had significantly higher enhancement ratings compared to 60 cc for all six structures assessed. The differences between groups ranged from -0.241 to -0.433 (p < 0.001) on the 5-point scale.The VGC analysis confirmed significantly greater brain parenchymal enhancement in the 80 cc group compared to the 60 cc group., Conclusion: The findings indicate that reducing the intravenous iodinated contrast material volume during brain CT from 80 cc to 60 cc leads to a statistically significant reduction in image quality and diagnostic accuracy. Further research with larger cohorts is needed to confirm these findings and assess the clinical impact of these differences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The hallmark of aluminum phosphide (AlP) poisoning is heart failure in victims which is associated with reactive oxygen species (ROS), mitochondrial dysfunction, oxidative stress, alteration in antioxidant defense system and depletion of ATP in cardiomyocytes. In the present study, we hypothesized that the injection of isolated mitochondria into blood or mitochondrial transplantation can likely create a primary target for phosphine released from AlP and inhibit AlP-induced mortality and cardiotoxicity in rat. Male, Wistar, healthy and adult rats were randomly divided into 5 groups as control, AlP (12.5 mg/kg, orally), AlP + mitochondria (125 µg/kg), AlP + mitochondria (250 µg/kg) and mitochondria (250 µg/kg) alone. Functional and intact mitochondria isolated from rat heart and transplantation was carried out via tail vein, 30 min after exposure to AlP. Survival rate, histopathological alterations, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters were monitored and analyzed during 30 days. We found that injection of healthy mitochondria into blood at concentrations of 125 and 250 125 µg/ml significantly increased the survival of rats up to 40% and 56.25% respectively, during 30 days. Moreover, we observed that mitochondria injection into blood decreased histopathological damages, cardiac biochemical markers, oxidative stress and mitochondrial toxicity parameters. To our knowledge, the current study is the first report in the literature that demonstrated good therapeutic effects of mitochondrial transplantation in AlP-induced mortality and cardiotoxicity. The findings of the present study suggests that injection of exogenous mitochondria into blood could be an effective therapeutic strategy in treating AlP poisoning., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nuclear medicine is an important tool for use in molecular imaging of important biological processes. Methods for intravenous delivery of radiotracers remains a challenge, with tail vein injections demonstrated to be technically difficult and lacking in reproducibility. Other intravenous methods include jugular vein (JV) injection, which requires a more invasive and precise microsurgical technique. Although the retroorbital (RO) sinus drains directly into the JV, and RO injections are minimally invasive and simpler to perform, they remain underutilized, perhaps due to a lack of studies demonstrating their performance. This study provides a comprehensive comparison of dynamic tissue biodistribution of three categories of commonly utilized radiopharmaceuticals between JV and RO injection methods in prostate tumor-bearing mice using PET-CT imaging. Results show that JV and RO injections have equivalent dynamic tissue biodistributions across the three categories of radiopharmaceuticals used: (1) small molecule measuring tumor metabolism ( 18 F-flurodeoxyglucose [FDG]); (2) peptide-based probe measuring angiogenesis ( 64 Cu-NOTA-PEG 4 -cRGD 2 ); and (3) dextran-based nanocarrier ( 64 Cu-NOTA-D20). Although RO injections present with some limitations such as type of injectate and difficulty for measuring acute, dynamic pharmacokinetics, this study demonstrates that RO injections are a viable, minimally invasive or stressful, and efficient alternative intravenous delivery technique for molecular imaging., (© 2024. The Author(s).)

Intravenous injectable metformin-Cu(II)-EGCG infinite coordination polymer nanoparticles (metformin-Cu(II)-EGCG ICP NPs) have been synthesized, and an efficient strategy for synergistic tumor therapy by utilizing these nanoparticles in conjunction with micro-electrothermal needles (MENs) was proposed. These nanoparticles display exceptional uniformity with a diameter of 117.5 ± 53.3 nm, exhibit an extraordinary drug loading capacity of 90% and allow for precise control over the drug ratio within the range of 1 : 1 to 1 : 20 while maintaining excellent thermal stability. Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and X-ray diffraction were employed to determine their chemical structure and coordination state. The combination index (CI) value of the metformin-Cu(II)-EGCG ICP NPs was calculated to be 0.19, surpassing that of the two individual drugs and metformin mixed with EGCG (0.98). Importantly, upon intravenous injection, metformin in nanoparticles demonstrated exceptional stability in the bloodstream, while both drugs were rapidly released within the acidic tumor microenvironment. Animal experiments showcased an impressive tumor inhibition rate of 100% within a mere 20-day time frame after the synergistic therapy with a lower dosage (5.0 mg kg -1 of nanoparticles), coupled with a minimal tumor recurrence rate of only 18.75% over a 60-day observation period. These findings indicate the promising prospects of these nanoparticles in tumor treatment.

Background: Heart failure mortality remains high despite recent progress in pharmacological treatment. AZD3427 is a selective long-acting analog of relaxin, a vasodilatory hormone with antifibrotic effects. We assessed the safety, pharmacokinetics, and pharmacodynamics of AZD3427 in healthy volunteers and patients with heart failure on standard-of-care therapy., Methods and Results: In this first-in-human, phase 1a/b, randomized, single-blind, placebo-controlled study, healthy volunteers were randomized 6:2 to receive a single dose of AZD3427 or placebo by subcutaneous injection in 5 mixed-ethnicity cohorts (5, 10, 30, 90, or 270 mg) and 1 Japanese-descent cohort (270 mg), or by intravenous injection in 1 cohort (15 mg). After confirming safety and tolerability in healthy volunteers, 3 cohorts of patients with heart failure and left ventricular ejection fraction ≤40% and 3 cohorts with ejection fraction ≥41% were randomized 6:2 to receive 5 weekly doses of AZD3427 (5, 15, or 45 mg) or placebo by subcutaneous injection. In total, 56 healthy volunteers and 48 patients with heart failure were randomized. AZD3427 was well tolerated at all doses. After subcutaneous administration, AZD3427 was absorbed slowly, and exposure was approximately linear across the dose range. In patients with heart failure, AZD3427 terminal half-life was 13 to 14 days and there were numerical increases in stroke volume and estimated glomerular filtration rate. No treatment-emergent antidrug antibodies were detected., Conclusions: AZD3427 had favorable safety and pharmacokinetic profiles. Hemodynamic changes in patients with heart failure were consistent with the anticipated effects of a relaxin analog. These findings support further development of AZD3427 as a novel long-term treatment for patients with heart failure., Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04630067.

Libtayo ® (cemiplimab-rwlc) injection for intravenous use was recently approved by the US Food and Drug Administration (FDA) for locally advanced basal cell carcinoma (laBCC) and metastatic basal cell carcinoma (mBCC), both being the advanced stages of BCC. In the past, it was approved by the FDA for the treatment of metastatic cutaneous squamous cell carcinoma (mCSCC) and locally advanced cutaneous squamous cell carcinoma (laCSCC), both being the advanced stages of CSCC. Cemiplimab is a monoclonal antibody that works by blocking the programmed death-1 pathway. In two open-label, single-arm, phase 2 studies, cemiplimab was investigated for the treatment of advanced stages of BCC (study 1620, NCT03132636) and advanced stages of CSCC (study 1540, NCT02760498). The primary endpoint was objec-tive response rate (ORR) per independent central review. In the study 1620, both mBCC and laBCC received cemiplimab 350 mg every 3 weeks. ORR was 21% (6/28) and 31% (26/84) in the mBCC and laBCC groups, respectively. In the study 1520, mCSCC was divided into two groups: one receiving cemiplimab 350 mg every 3 weeks (Q3W) and another receiving 3-mg/kg cemiplimab every 2 weeks (Q2W); the third group, laCSCC, received cemiplimab 3 mg/kg every 2 weeks. ORR was 41% (23/56) in the Q3W group, 49% (29/59) in the Q2W group, and 44% (34/78) in the laCSCC group. An acceptable safety profile and antitumor activity was discovered in patients treated with cemiplimab. The recommended dosage for cemiplimab to treat advanced stages of BCC and CSCC is 350 mg every 3 weeks administered intravenously over 30 min.

Background: Sanfilippo syndrome (mucopolysaccharidosis type IIIA; MPS IIIA) is a childhood dementia caused by inherited mutations in the sulfamidase gene. At present, there is no treatment and children with classical disease generally die in their late teens. Intravenous or intra-cerebrospinal fluid (CSF) injection of AAV9-gene replacement is being examined in human clinical trials; evaluation of the impact on brain disease is an intense focus; however, MPS IIIA patients also experience profound, progressive photoreceptor loss, leading to night blindness., Aim: To compare the relative efficacy of the two therapeutic approaches on retinal degeneration in MPS IIIA mice., Methods: Neonatal mice received i.v. or intra-CSF AAV9-sulfamidase or vehicle and after 20 weeks, biochemical and histological evaluation of neuroretina integrity was carried out., Results: Both treatments improved central retinal thickness; however, in peripheral retina, outer nuclear layer thickness and photoreceptor cell length were only significantly improved by i.v. gene replacement. Further, normalization of endo-lysosomal compartment size and microglial morphology was only observed following intravenous gene delivery., Conclusions: Confirmatory studies are needed in adult mice; however, these data indicate that i.v. AAV9-sulfamidase infusion leads to superior outcomes in neuroretina, and cerebrospinal fluid-delivered AAV9 may need to be supplemented with another therapeutic approach for optimal patient quality of life., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Purpose: To summarize recent cases of fatal insulin poisoning both domestically and internationally, thereby offering valuable insights for the forensic identification of insulin overdose cases., Methods: Literature published since 2000 on fatal insulin overdose were systematically searched and screened. Data encompassing variables such as year, age, sex, cause of death, scene conditions, occupations, medical histories of victims and perpetrators, autopsy timing, dosage and administration methods, forensic pathology, and toxicological analysis, were compiled for rigorous statistical analysis., Results: Among the 29 fatal cases of insulin poisoning, suicides and homicides accounted for 55.2 % and 41.4 %, respectively. Precisely 34.5 % of victims or perpetrators were associated with the medical industry, 27.6 % had diabetes, and 24.1 % had mental illnesses such as depression. Intravenous injection resulted in quicker death than did subcutaneous injection. In some cases, immunohistochemical staining of insulin and protamine at injection sites yielded positive results. The average molar ratio of insulin to C-peptide in post-mortem blood was 13.76 ± 5.167, indicating a significant diagnostic value for insulin poisoning., Conclusion: Assessment of cases of fatal insulin overdose should be thorough, incorporating case investigation, scene examination, medical records review, autopsy findings, pathological examinations, and laboratory tests, alongside considering the condition of the body and timing of death autopsy. Using mass spectrometry to detect insulin proves valuable, particularly in cases of poor body preservation., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Pain related to injection of propofol during induction of anesthesia decreases from 66.8% without prevention, to 22-31% of cases when lidocaine is associated. Hypnoanalgesia of the hand is currently used for painful procedures in children but has never been evaluated in this indication. The primary aim of this prospective randomized single-blind study was to evaluate the efficacy of hypnoanalgesia of the hand for the prevention of moderate to severe pain during intravenous injection of propofol alone in comparison to lidocaine admixture. The secondary aim was to compare the global satisfaction of children in both methods., Patients and Methods: One hundred patients aged 7-14 years, ASA 1-2, admitted for scheduled surgery under general anesthesia were randomized into two groups. Group L received a mixture of 1% propofol (3 mg/kg) and 1% Lidocaine (0.3 mg/kg). Group H received 1% propofol (3 mg/kg) after hypnoanalgesia of the hand realized by a single experimented operator. A video was made in order to evaluate the pain related to propofol injection by a blinded observer using the 4-point score of Cameron (painful ≥ 2). The global satisfaction of children was evaluated in postanesthesia care unit and documented if visual analog score was <7/10., Results: Ninety-six patients were analyzed. The rate of painful patients did not differ significantly between groups (8.5% in group H [n = 47] vs 6.1% in group L [n = 49], OR= 0.70; 95% CI [0.13-3.35], p = 0.65), nor did the rate of nonsatisfied patients (10.6 in group H vs. 12.2% in group L, OR = 0.85; 95% CI [0.19-3.65], p = 1)., Conclusions: Our results suggest that hypnoanalgesia of the hand alone is effective to prevent the pain related to propofol injection in children. No significant difference was found in comparison with lidocaine admixture nor for pain or satisfaction., (© 2024 The Authors. Pediatric Anesthesia published by John Wiley & Sons Ltd.)

Objective: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest., Design: Cluster randomised controlled trial., Setting: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic., Participants: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest., Interventions: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access., Main Outcome Measures: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge., Results: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes., Conclusions: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes., Trial Registration: NCT04135547ClinicalTrials.gov NCT04135547., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: this study was supported by the Taiwan Ministry of Science and Technology, National Science and Technology Council, and National Taiwan University Hospital, Yun-Lin Branch; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There are few reports of poisoning caused by high-dose intravenous injection of mercury. Its clinical manifestations are diverse and the risk of mortality is high. Currently, the pathogenesis is not clear and the treatment experience is insufficient, leading to difficulties in clinical diagnosis and treatment. In this article, the data of a case of mercury poisoning caused by intravenous self-administration was analyzed and summarized. The patient developed multiple organ dysfunction syndrome after intravenous injection of high-dose mercury. After comprehensive treatment, such as mercury removal, organ support, and infection prevention, the condition was improved. This case suggests that intravenous injection of mercury can cause damage to the functions of multiple organs, such as the heart, lungs, and kidneys. Early treatment and intervention can bring benefits.

Background: In patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels., Methods: In this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated., Results: Compared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively., Conclusion: Perioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl., Trial Registration: Chinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760 ., (© 2024. The Author(s).)

Information on the physical compatibility of intravenous (IV) medications is vital for patient care and safety in acute care settings. Drug information resources list ondansetron and nafcillin as IV compatible, however, bolus concentrations of ondansetron are not reported. This study investigated the in vitro physical compatibility of bolus and infusion concentrations of ondansetron hydrochloride with nafcillin sodium. Two admixtures were prepared: 1) ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL, and 2) ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL. The admixtures were prepared in triplicate using aseptic technique according to manufacturer guidance and stored at room temperature (22-23 °C) for up to 24 hours. Admixtures were examined for visual precipitation, turbidity, and pH at baseline and at 1, 5, 8, and 24 hours. Admixture 1 developed a haze immediately after mixing, which was sustained over 24 hours. There was a demonstrative change in absorbance after 1 hour, but pH remained stable until hour 24. Admixture 2 developed a haze at 5 hours, but the absorbance and pH remained stable until hour 24; a decrease in the pH was observed in all samples at hour 24. This in vitro study revealed that ondansetron hydrochloride 2 mg/mL and nafcillin sodium 20 mg/mL are not physically compatible when administered through the same IV line. No demonstrative change was observed with ondansetron hydrochloride 0.16 mg/mL and nafcillin sodium 20 mg/mL; however, concurrent administration of these medications is questionable when delivered through an IV line for periods of five hours or longer., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

E3112 is a recombinant human hepatocyte growth factor which is under development for the treatment of acute liver failure. Pharmacokinetics (PK) evaluation in experimental animals is important and thus a simple assay for the determination of E3112 in rat and monkey serum has been validated using a commercially available enzyme-linked immunosorbent assay (ELISA) kit. E3112 in rat and monkey serum was quantifiable from 0.313 ng/mL to 15.0 ng/mL without prozone effects. Dilution integrity enabled accurate assay up to 500,000-fold dilution. Accuracy and precision were within the acceptance criteria. PK of E3112 was investigated after intravenous administration to rats and monkeys. PK of E3112 was similar between male and female animals in both species. Nonlinear PK of E3112 was observed in rats after intravenous bolus dose at 1-100 mg/kg while nonlinear PK was not significant in monkeys after intravenous infusion at 0.5-25 mg/kg. These findings suggest that the assay of E3112 in serum using a commercially available ELISA kit was validated and successfully applied to PK studies in rats and monkeys., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Herein, we present the case of accidental intravenous injection of gasoline in a 62-year-old male who was admitted to a dialysis center for his regular hemodialysis. Due to previous contact with another SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) positive patient, the hemodialysis was conducted in an isolated room. At the end of the procedure, the nurse, wearing all necessary personal protective equipment (PPE), in the intent to clean the dialysis catheter, applied medical gasoline, instead of 0.9% sodium chloride, intravenously to the patient. Soon afterwards, the patient's clinical condition deteriorated, and cardiopulmonary resuscitation was started. Despite the immediate reaction of the medical staff, after two successful cardiopulmonary reanimation and necessary intensive care measures, the patient suffered respiratory, metabolic, and lactic acidosis, hypotension, and tachyarrhythmia and ultimately died 7 h after the incident. The autopsy was conducted under the order of the district attorney. Main autopsy findings were marked congestion; right pleural and pericardial effusion; brain and lung edema; enlarged heart with left ventricle thickening and mild perivascular fibrosis; nephrosclerosis; tubular thyroidization; and interstitial fibrosis with inflammation. Gasoline presence was indisputably proven by conducted toxicology analysis in lung, bile, and brain samples. Traces of gasoline could be noted in the patient's blood sample in comparison to the blood that did not contain gasoline, but it was not possible to confidently claim that gasoline was present in the blood. Based on relevant findings, we concluded that the death of the patient was violent and that the cause of death was acute intoxication by gasoline., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The incidence of arterial hypotension during induction of general anesthesia is influenced by the method of propofol administration, but there is a dearth of randomized clinical trials comparing bolus injection and target-controlled infusion in relation to arterial hypotension. This study seeks to compare the incidence of arterial hypotension between these two methods of propofol administration., Methods: This prospective, randomized, single-center, non-blinded study included 60 patients (aged 35 to 55 years), classified as ASA physical status I or II, who were undergoing non-cardiac surgeries. They were randomly allocated using a computer to two groups based on the method of propofol administration during the induction of general anesthesia: the Target Group, receiving target-controlled infusion at 4 μg.mL -1 , and the Bolus Group, receiving a bolus infusion of 2 mg.kg -1 . Both groups also received midazolam 2 mg, fentanyl 3 μg.kg -1 , and rocuronium 0.6 mg.kg -1 . Over the first 10 minutes of anesthesia induction, Mean Arterial Pressure (MAP), Heart Rate (HR), level of Consciousness (qCON), and Suppression Rate (SR) were recorded every 2 minutes., Results: Twenty-seven patients remained in the TCI group, while 28 were in the Bolus group. Repeated measure analysis using mixed-effects models could not reject the null hypothesis for the effect of group-time interactions in MAP (p = 0.85), HR (p = 0.49), SR (p = 0.44), or qCON (p = 0.72). The difference in means for qCON (60.2 for TCI, 50.5 for bolus, p < 0.001), MAP (90.3 for TCI, 86.2 for bolus, p < 0.006), HR (76.2 for TCI, 76.9 for bolus, p = 0.93), and SR (0.01 for TCI, 5.5 for bolus, p < 0.001), irrespective of time (whole period means), revealed some significant differences., Conclusion: Patients who received propofol bolus injection exhibited a lower mean arterial pressure, a greater variation in the level of consciousness, and a higher suppression rate compared to those who received it as a target-controlled infusion. However, the interaction effect between groups and time remains inconclusive., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection, with great clinical heterogeneity, high morbidity, and high mortality. At the same time, there are many kinds of infection sources, the pathophysiology is very complex, and the pathogenesis has not been fully elucidated. An ideal animal model of sepsis can accurately simulate clinical sepsis and promote the development of sepsis-related pathogenesis, treatment methods, and prognosis. The existing sepsis model still uses the previous Sepsis 2.0 modelling standard, which has some problems, such as many kinds of infection sources, poor repeatability, inability to take into account single-factor studies, and large differences from clinical sepsis patients. To solve these problems, this study established a new animal model of sepsis. The model uses intravenous tail injection of a single bacterial strain, simplifying the complexity of multibacterial infection, and effectively solving the above problems.

Aims: Cancer-related thrombosis (CAT) is a common complication in cancer patients, significantly impacting their quality of life and survival prospects. Nattokinase (NK) has potent thrombolytic properties, however, its efficacy is limited by low oral bioavailability and the risk of severe allergic reactions with intravenous use. Heparin (HP) is a widely used anticoagulant in clinical settings. This study aimed to overcome the intravenous toxicity of NK and explore its effect on CAT in advanced tumors., Main Methods: In this study, NK-HP electrostatic complexes were constructed, and their safety and thrombolytic efficacy were verified through guinea pig allergy tests, mouse tail vein tests, and both in vivo and in vitro thrombolysis experiments. Additionally, an S180 advanced tumor model was developed and combined with sialic acid-modified doxorubicin liposomes (DOX-SAL) to investigate the impact of NK-HP on CAT and its antitumor effects in advanced tumors., Key Findings: We observed that NK-HP can eliminate the intravenous injection toxicity of NK, has strong thrombolytic performance, and can prevent thrombosis formation. Intravenous injection of NK-HP can enhance the antitumor effect of DOX-SAL by reducing the fibrin content in advanced tumors and increasing the levels of the cross-linked protein degradation product D-dimer., Significance: This study developed a method to eliminate the intravenous injection toxicity of NK, proposing a promising therapeutic strategy for CAT treatment, particularly for CAT in advanced tumors, and improving the efficacy of nano-formulations in anti-tumor therapy., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2024. Published by Elsevier Inc.)

OBJECTIVES: To compare the defervescence period of azithromycin versus ceftriaxone in children with enteric fever. METHODS: This open-label, randomized-controlled trial was conducted at Pediatrics Department, Federal Government Polyclinic Hospital, Islamabad, Pakistan from June 30, 2015 to December 30, 2015. Sample Size calculated was 99 by using WHO Sample Size Calculator. Patients of either gender, aging 2-12 years, diagnosed as enteric fever were eligible for study. One hundred eligible patients selected through non-probability consecutive sampling technique were recruited in the study, after seeking an informed consent from the parents. These patients were randomized through lottery method in two groups of equal size (n=50 each). Group A, received oral azithromycin suspension/capsule (10mg/kg/day; maximum dose, 500mg/day) administered once daily for 7 days, while Group B received intravenous (I/V) ceftriaxone (75mg/kg/day; maximum dose, 2.5 g/day) administered twice daily for 10 days. The clinical response to the therapy of both drugs was calculated in terms of number of days taken for defervescence. Data was analyzed in SPSS version 22.0. RESULTS: Out of 100 patients, 64 (64%) were males and 36 (36%) were females and mean age of patients was 7.08±3.013 years. Patients on azithromycin had the mean time of defervescence 4.08±0.922 days and patients on ceftriaxone, the mean time of defervescence was 4.06±1.038 (p=0.919). CONCLUSION: There is no significant difference between oral azithromycin and intravenous ceftriaxone in term of defervescence period for the treatment of enteric fever in children. azithromycin could be a suitable alternative owing to its convenient dosing and monitored on outpatient basis.

We aimed to produce a mouse model of spinocerebellar ataxia type 3 (SCA3) using the mouse blood-brain barrier (BBB)-penetrating adeno-associated virus (AAV)-PHP.B. Four-to-five-week-old C57BL/6 mice received injections of high-dose (2.0 × 10 11 vg/mouse) or low-dose (5.0 × 10 10 vg/mouse) AAV-PHP.B encoding a SCA3 causative gene containing abnormally long 89 CAG repeats [ATXN3(Q89)] under the control of the ubiquitous chicken β-actin hybrid (CBh) promoter. Control mice received high doses of AAV-PHP.B encoding ATXN3 with non-pathogenic 15 CAG repeats [ATXN3(Q15)] or phosphate-buffered saline (PBS) alone. More than half of the mice injected with high doses of AAV-PHP.B encoding ATXN3(Q89) died within 4 weeks after the injection. No mice in other groups died during the 12-week observation period. Mice injected with low doses of AAV-PHP.B encoding ATXN3(Q89) exhibited progressive motor uncoordination starting 4 weeks and a shorter stride in footprint analysis performed at 12 weeks post-AAV injection. Immunohistochemistry showed thinning of the molecular layer and the formation of nuclear inclusions in Purkinje cells from mice injected with low doses of AAV-PHP.B encoding ATXN3(Q89). Moreover, ATXN3(Q89) expression significantly reduced the number of large projection neurons in the cerebellar nuclei to one third of that observed in mice expressing ATXN3(Q15). This AAV-based approach is superior to conventional methods in that the required number of model mice can be created simply by injecting AAV, and the expression levels of the responsible gene can be adjusted by changing the amount of AAV injected. Moreover, this method may be applied to produce SCA3 models in non-human primates.

Background: Alteplase is the standard agent used in early reperfusion therapy, but alternative thrombolytic agents are needed. The efficacy and safety of reteplase as compared with alteplase in patients with acute ischemic stroke are unclear., Methods: We randomly assigned patients with ischemic stroke within 4.5 hours after symptom onset in a 1:1 ratio to receive intravenous reteplase (a bolus of 18 mg followed 30 minutes later by a second bolus of 18 mg) or intravenous alteplase (0.9 mg per kilogram of body weight; maximum dose, 90 mg). The primary efficacy outcome was an excellent functional outcome, defined as a score of 0 or 1 on the modified Rankin scale (range, 0 [no neurologic deficit, no symptoms, or completely recovered] to 6 [death]) at 90 days. The primary safety outcome was symptomatic intracranial hemorrhage within 36 hours after symptom onset., Results: A total of 707 patients were assigned to receive reteplase, and 705 were assigned to receive alteplase. An excellent functional outcome occurred in 79.5% of the patients in the reteplase group and in 70.4% of those in the alteplase group (risk ratio, 1.13; 95% confidence interval [CI], 1.05 to 1.21; P<0.001 for noninferiority and P = 0.002 for superiority). Symptomatic intracranial hemorrhage within 36 hours after disease onset was observed in 17 of 700 patients (2.4%) in the reteplase group and in 14 of 699 (2.0%) of those in the alteplase group (risk ratio, 1.21; 95% CI, 0.54 to 2.75). The incidence of any intracranial hemorrhage at 90 days was higher with reteplase than with alteplase (7.7% vs. 4.9%; risk ratio, 1.59; 95% CI, 1.00 to 2.51), as was the incidence of adverse events (91.6% vs. 82.4%; risk ratio, 1.11; 95% CI, 1.03 to 1.20)., Conclusions: Among patients with ischemic stroke within 4.5 hours after symptom onset, reteplase was more likely to result in an excellent functional outcome than alteplase. (Funded by China Resources Angde Biotech Pharma and others; RAISE ClinicalTrials.gov number, NCT05295173.)., (Copyright © 2024 Massachusetts Medical Society.)

Immune modulation through the intracellular delivery of nucleoside-modified mRNA to immune cells is an attractive approach for in vivo immunoengineering, with applications in infectious disease, cancer immunotherapy, and beyond. Lipid nanoparticles (LNPs) have come to the fore as a promising nucleic acid delivery platform, but LNP design criteria remain poorly defined, making the rate-limiting step for LNP discovery the screening process. In this study, we employed high-throughput in vivo LNP screening based on molecular barcoding to investigate the influence of LNP composition on immune tropism with applications in vaccines and systemic immunotherapies. Screening a large LNP library under both intramuscular ( i.m. ) and intravenous ( i.v. ) injection, we observed differential influences on LNP uptake by immune populations across the two administration routes, gleaning insight into LNP design criteria for in vivo immunoengineering. In validation studies, the lead LNP formulation for i.m. administration demonstrated substantial mRNA translation in the spleen and draining lymph nodes with a more favorable biodistribution profile than LNPs formulated with the clinical standard ionizable lipid DLin-MC3-DMA (MC3). The lead LNP formulations for i.v. administration displayed potent immune transfection in the spleen and peripheral blood, with one lead LNP demonstrating substantial transfection of splenic dendritic cells and another inducing substantial transfection of circulating monocytes. Altogether, the immunotropic LNPs identified by high-throughput in vivo screening demonstrated significant promise for both locally- and systemically-delivered mRNA and confirmed the value of the LNP design criteria gleaned from our screening process, which could potentially inform future endeavors in mRNA vaccine and immunotherapy applications.

Purpose: Shivering occurs frequently after caesarean delivery. The present study aimed to investigate the ED50 and ED95 of an intravenous (i.v.) bolus of dexmedetomidine for treating severe shivering after caesarean delivery under combined spinal-epidural anaesthesia., Patients and Methods: Seventy-five parturients with severe shivering after caesarean delivery were randomized into one of the five groups to receive an i.v. bolus of 0.2 (Group D1), 0.25 (Group D2), 0.3 (Group D3), 0.35 (Group D4) or 0.4 (Group D5) μg/kg of dexmedetomidine. Effectiveness of shivering treatment was defined as a standardized shivering score decreasing to ≤1 within 10 min of dexmedetomidine injection. The ED50 and ED95 were determined by probit regression. Adverse effects were also compared among the groups., Results: The ED50 and ED95 of i.v. dexmedetomidine to treat severe shivering were 0.23 (95% CI, 0.16-0.26) μg/kg and 0.39 (95% CI, 0.34-0.52) μg/kg, respectively. No difference in the incidence of adverse effects was found between groups., Conclusion: An i.v. bolus of 0.39 μg/kg of dexmedetomidine will treat 95% of parturients experiencing severe shivering after caesarean delivery., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Yang et al.)

Background: Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized., Methods: In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed., Results: The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells., Conclusions: Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). Published by IMR Press.)

Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep., Competing Interests: The authorship has no competing interest with this work., (Copyright: © 2024 Smith et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Metabolic syndrome (MetS) is a significant epidemiological problem worldwide. It is a pre-morbid, chronic and low-grade inflammatory disorder that precedes many chronic diseases. Wharton's jelly-derived mesenchymal stem cells (WJ-MSCs) could be used to treat MetS because they express high regenerative capacity, strong immunomodulatory properties and allogeneic biocompatibility. This study aims to investigate WJ-MSCs as a therapy against MetS in a rat model., Methods: Twenty-four animals were fed with high-fat high-fructose (HFHF) diet ad libitum. After 16 weeks, the animals were randomised into treatment groups (n = 8/group) and received a single intravenous administration of vehicle, that is, 3 × 10 6 cells/kg or 10 × 10 6 cells/kg of WJ-MSCs. A healthy animal group (n = 6) fed with a normal diet received the same vehicle as the control (CTRL). All animals were periodically assessed (every 4 weeks) for physical measurements, serum biochemistry, glucose tolerance test, cardiovascular function test and whole-body composition. Post-euthanasia, organs were weighed and processed for histopathology. Serum was collected for C-reactive protein and inflammatory cytokine assay., Results: The results between HFHF-treated groups and healthy or HFHF-CTRL did not achieve statistical significance (α = 0.05). The effects of WJ-MSCs were masked by the manifestation of different disease subclusters and continuous supplementation of HFHF diet. Based on secondary analysis, WJ-MSCs had major implications in improving cardiopulmonary morbidities. The lungs, liver and heart show significantly better histopathology in the WJ-MSC-treated groups than in the untreated CTRL group. The cells produced a dose-dependent effect (high dose lasted until week 8) in preventing further metabolic decay in MetS animals., Conclusions: The establishment of safety and therapeutic proof-of-concept encourages further studies by improving the current therapeutic model., (© 2024. The Author(s).)

Background: In this study, the early and mid-term outcomes of sartorius flap reconstruction after the development of a prior groin infection were investigated., Methods: From January 2017 until June 2023, 44 patients from 2 centers in Italy underwent sartorius flap reconstruction after the development of a prior groin infection. Thirty-day outcome measures including major morbidity, amputation-free survival, and mortality were assessed. At 2-year follow-up, estimated outcomes of freedom from hemorrhagic complications, freedom from recurrent infection, freedom from reintervention, and amputation-free survival were analyzed using Kaplan-Meier curves., Results: In 35 cases (79.5%) a previous vascular procedure was performed, whilst in the remaining 9 cases (20.5%) the patient was an intravenous drug abuser. Thirty-day mortality and major amputation rates were 4.5%, and 2.3%, respectively. Overall 30-day wound healing rate was 56.8% (25 cases). The overall median duration of follow-up was 12 months (IQR 4-24). Complete wound healing was obtained in 36 cases (81.8%) after a median period of 1 month (IQR 1-3). The 2-year Kaplan-Meier estimates of freedom from hemorrhagic complications, freedom from recurrent infection, freedom from reintervention, and amputation-free survival were 82.1%, 70%, 71.9%, and 97.7%, respectively. Multivariate analysis confirmed the association of female sex with recurrent infection (HR 3.4, P=.05)., Conclusions: Sartorius flap reconstruction after the development of a prior groin infection following vascular procedures or intravenous drug injections yielded acceptable mid-term outcomes in terms of freedom from hemorrhagic complications, and freedom from recurrent infection. Female sex seemed to affect the rate of recurrent infection.

As one of the most common iron-chelating agents, deferoxamine (DFO) rapidly chelates iron in the body. Moreover, it does not compete for the iron characteristic of hemoglobin in the blood cells, which is common in the clinical treatment of iron poisoning. Iron is a trace element necessary to maintain organism normal life activities. Iron deficiency can lead to anemia, whereas iron overload can cause elevated levels of cellular oxidative stress and cell damage. As a consequence, detection of the iron content in tissues and blood is of great significance. The traditional techniques for detecting the iron content include inductively coupled plasma-mass spectrometry and atomic absorption spectrometry, which cannot be used for imaging purposes. Laser ablation-ICP-MS and synchrotron radiation micro-X-ray fluorescence can map the concentration and distribution of iron in tissues. However, these methods can only be used to measure the total iron levels in blood or tissues. In recent years, due to the deepening understanding of iron metabolism, diseases related to iron overload have attracted increasing attention. Therefore, we took advantage of the properties of DFO in terms of chelating iron and investigated different sampling times following DFO injection in the tail vein of mice. We used mass spectrometry imaging (MSI) technology to detect the DFO and ferrioxamine content in the blood and different tissues to indirectly characterize the non-heme iron content., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: The purpose of this study is to compare the opioid requirement and pain intensity after surgeries of mandibular fractures with administration of dexmedetomidine by two approaches of infusion and single bolus., Methods: In this double-blind clinical trial, the participants were randomized and matched in terms of age and gender in two groups (infusion and bolus). In both groups, the amount of narcotic used, hemodynamic indices, oxygen saturation, and pain intensity were collected based on the ten-point Visual Analogue Scale (VAS) at 7 time points for 24 h. SPSS version 24 software was used for data analysis. A significance level of less than 5% was considered., Results: A total of 40 patients were included in the study. There was no significant difference between the two groups in terms of gender, age, ASA class, and duration of surgery (P>0.05). There was no significant difference between the two groups in terms of nausea and vomiting and subsequently receiving anti-nausea medication (P>0.05). The need for opioid consumption after surgery was not different in two groups (P>0.05). Infusion of dexmedetomidine reduced postoperative pain more rapidly than its single bolus dose (P<0.05). However, over time, there was no significant difference between the two groups in terms of changes in oxygen saturation variables (P>0.05). Homodynamic indices including heart rate, systolic blood pressure, and diastolic blood pressure in the bolus group were significantly lower than the infusion group (P<0.05)., Conclusion: Administration of dexmedetomidine in the form of infusion can reduce postoperative pain better than bolus injection, with less probability of hypotension and bradycardia., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Tranexamic acid (TXA) administration is supported by numerous evidence in reducing blood loss after total knee arthroplasty (TKA). The combination of intravenous (IV) and intra-articular (IA) TXA administration revealed good result in blood loss reduction with less evidence of venous thromboembolism event (VTE). Several literature reviews portray that peri-articular (PA) administration yields similar hemostasis in comparison to IV route. However, there is no report on the clinical effect of combining PA + IA TXA in blood loss reduction and its complications, compared to combining IV + IA TXA after TKA., Materials and Methods: We conducted a double-blind, randomized controlled trial comparing the use of PA + IA TXA administration and IV + IA TXA administration in 70 patients who were scheduled for unilateral primary TKA. Thirty-five patients were assigned for PA + IA injection (Group 1) and anoter 35 patients were assigned for IV + IA injection (Group 2). Primary outcomes included total blood loss at 48 h, and the need for blood transfusion. Secondary outcomes included thigh and leg circumference, degree of knee flexion, and postoperative complications., Results: The calculated blood loss at 48 h showed no difference between Groups 1 and 2 (617 ml vs. 632 ml, p = 0.425). The total hemoglobin and hematocrit changes were not different (1.89 g/dL vs. 1.97 g/dL, p = 0.371 and 5.66% vs. 5.87%, p = 0.391). There was no need for blood transfusion in either group. However, lower thigh swelling was significant in Group 1 (2.15 cm vs. 2.79 cm, p = 0.04). Leg circumferences at 48 h was also lower in Group 1 (42.12 cm vs. 42.77 cm, p = 0.04). There was no significant difference in knee flexion decrease between the two groups (38° vs. 37°, p = 0.425). There were no VTE complications or infections found in either group., Conclusions: Combined PA + IA TXA administration had similar efficacy in blood loss reduction and blood transfusion when compared to combined IV + IA TXA. The first group displayed less soft tissue swelling. The combination of PA + IA TXA administration can be used as an alternative regimen to avoid IV TXA administration., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Propofol for anesthesia has become increasingly popular for endoscopic procedures. However, pain on propofol injection (POPI) remains an issue with administration. The primary endpoint of this study was to identify patient characteristics and factors, such as IV site and gauge, that could predict the occurrence of POPI., Methods: This was a prospective chart review study of 291 patients undergoing endoscopic procedures. The patient's demographics, intravenous (IV) site, and gauge were extrapolated. POPI was scored 0-3: 0 for no pain, 1 for minimal discomfort or awareness of sensation, 2 for discomfort but manageable/tolerable, and 3 for severe discomfort with writhing., Results: 291 patient charts were reviewed. One patient was excluded for a lower extremity IV site. 225 (77.6%) had no pain, 48 (16.6%) grade 1 pain, 16 (5.5%) grade 2 pain, and 1 (0.3%) grade 3 pain. 137, 13, and 140 patients respectively had antecubital (AC), forearm, and hand IVs. Zero patients with an AC IV experienced a score greater than 1. Compared to AC, forearm IVs with pain of 2-3 had a univariate odds ratio (OR) of 11.3 (0.66,1.92; p-value < 0.001), and hand IVs had a univariate OR of 18.8 (2.46,143.3; p-value < 0.001) with a multivariable OR 15.2 (1.93,118.9; p-value 0.004). Patients with anxiety/depression and pain had a univariate OR 2.31 (1.09, 7.27; p-value 0.031) with a multivariable OR 2.85 (1.06, 7.74; p-value 0.039). SSRI/SNRI use had a univariate OR 1.56 (0.57,4.28; p-value 0.38). Alcohol use had a univariate OR 1.24 (0.39,3.91; p-value 0.71). Narcotic use had a Univariate OR 6.18 (1.49,25.6; p-value 0.012). Diabetic patients had a univariate OR of 1.42 (0.45,4.48; p-value 0.55). Chronic pain had a univariate OR of 3.11 (1.04,9.28; p-value 0.042). Females had a univariate OR 0.98 (0.37,2.63; p-value 0.95)., Conclusion: This study identified potential characteristics for having POPI. The incidence of POPI was statistically significant in patients with hand and forearm IVs compared to AC IV sites, larger IV gauges, history of depression/anxiety, history of chronic narcotic use, fibromyalgia, and chronic pain syndromes. This shows the potential of premedicating with analgesics or using AC sites on these select patients to help reduce the risk of POPI., (© 2024. The Author(s).)

Background: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload., Objectives: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults., Search Methods: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024., Selection Criteria: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors., Data Collection and Analysis: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence., Main Results: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I 2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I 2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I 2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I 2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I 2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I 2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics., Authors' Conclusions: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Glucocorticoids have been widely used in perioperative period for postoperative pain relief after total knee arthroplasty (TKA). However, the optimal administration protocols of glucocorticoids remain controversial. This study aims to compare the efficacy of glucocorticoids between intravenous and periarticular injection on clinical outcomes., Methods: A total of 114 patients were randomly assigned to intravenous (IV) group ( n = 57) and periarticular injection (PI) group ( n = 57). The IV group received 10 mg dexamethasone intravenously and the PI group received periarticular injection of 10 mg dexamethasone during the procedure. The clinical outcomes were assessed using visual analogue scale (VAS), knee society score (KSS), range of motion (ROM), knee swelling, inflammation markers and complications after TKA., Results: The VAS score during walking at 2nd day postoperatively was lower in the PI group compared with the IV group (2.08 ± 1.45 vs 2.73 ± 1.69, p = .039), and there was no significant difference at the other time points of VAS score in two groups. The inflammation markers, knee swelling, knee ROM and KSS score were not statistically different. Vomiting and other complications occurrence were not significantly different between the two groups., Conclusions: Intraoperative periarticular injection of glucocorticoids has similar analgesic effect compared to intravenous in the postoperative period following TKA and may be even more effective on the second postoperative day. In addition, periarticular injection of glucocorticoids does not impose an excess risk or complication on patients., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Even though subconjunctival injections are used in clinics, their quantitative pharmacokinetics has not been studied systematically. For this purpose, we evaluated the ocular and plasma pharmacokinetics of subconjunctival dexamethasone in rabbits. Intravenous injection was also given to enable a better understanding of the systemic pharmacokinetics. Dexamethasone concentrations in plasma (after subconjunctival and intravenous injections) and four ocular tissues (iris-ciliary body, aqueous humour, neural retina and vitreous) were analysed using LC-MS/MS. Population pharmacokinetic modelling for plasma data from both injection routes were used, and for first time the constant rate of absorption of dexamethasone from the subconjunctival space into plasma was estimated (k a,plasma  = 0.043 min -1 , i.e. absorption half-life of 17.3 min). Non-compartmental analysis was used for the ocular data analysis and resulting in ocular drug exposure of iris-ciliary body (AUC 0-∞ = 41984 min·ng/g) > neural retina (AUC 0-∞ = 25511 min·ng/g) > vitreous (AUC 0-∞ = 7319 min·ng/mL) > aqueous humour (AUC 0-∞ = 6146 min·ng/mL). The absolute bioavailability values after subconjunctival injection, reported for the first time, were 0.74 % in aqueous humour (comparable to topical dexamethasone suspensions), and 0.30 % in vitreous humour (estimated to be higher than in topical administration). These novel and comprehensive pharmacokinetic data provide valuable information on the potential for exploiting this route in ocular drug development for treating both, anterior and posterior segment ocular diseases. Moreover, the new generated dexamethasone-parameters are a step-forward in building predictive pharmacokinetic models to support the design of new subconjunctival dexamethasone formulations, which may sustain drug effect for longer period of time., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the hepatic effects of high-dose intravenous (IV) iron, including those on liver function and the degree of fibrosis, in a rat model of cirrhosis., Methods: We evenly allocated 25 Sprague-Dawley rats into five groups: normal rats (control group), cirrhotic rats receiving IV normal saline (liver cirrhosis [LC] group), and cirrhotic rats receiving 20, 40, or 80 mg/kg IV ferric carboxymaltose (LC-iron20, LC-iron40, and LC-iron80 group, respectively). Biochemical parameters were compared at 0, 7, 14, 21, and 28 days. The degrees of hepatic fibrosis and iron deposition were evaluated. Inflammatory and oxidative stress markers were also compared., Results: There were no significant differences in the 28-day serum alanine aminotransferase levels among the LC-iron20, LC-iron40, and LC-iron80 groups (69 ± 7, 1003 ± 127, 1064 ± 309, 919 ± 346, and 820 ± 195 IU/L in the control, LC, LC-iron20, LC-iron40, and LC-iron80 groups, respectively). Hepatic iron accumulation increased in a dose-dependent manner, but the degree of hepatic fibrosis was comparable among the groups. The inflammatory and oxidative stress marker levels did not differ significantly according to the IV iron dose., Conclusions: Administration of IV iron at various high doses appears safe in our rat model of cirrhosis., Competing Interests: Declaration of conflicting interestsThe authors declare that there is no conflict of interest.

Background: Acute gastrointestinal bleeding (AGIB) is common in older patients but the use of iron in this context remains understudied., Aims: This study aimed to evaluate prospectively the efficacy of ferric carboxymaltose to treat anaemia in older patients after AGIB., Methods: This randomised double-blinded placebo-controlled clinical trial was conducted in 10 French centres. Eligible patients were 65 years or more, had controlled upper or lower gastrointestinal bleeding and a haemoglobin level of 9-11 g/dl. Patients were randomly assigned, in a 1:1 ratio, to receive either one intravenous iron injection of ferric carboxymaltose or one injection of saline solution. The primary endpoint was the difference in haemoglobin level between day 0 and day 42. Secondary endpoints were treatment-emergent adverse events, serious adverse events, rehospitalisation and improvement of quality of life (QOL) at day 180., Results: From January 2013 to January 2017, 59 patients were included. The median age of patients was 81.9 [75.8, 87.3] years. At day 42, a significant difference in haemoglobin level increase was observed (2.49 g/dl in the ferric carboxymaltose group vs. 1.56 g/dl in the placebo group, P = 0.02). At day 180, QOL, measured on European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, improved by 10.5 points in the ferric carboxymaltose group and by 8.2 points in the placebo group (P = 0.56). Rates of adverse events and rehospitalisation were similar in the two groups., Conclusions: Intravenous iron seems safe and effective to treat anaemia in older patients after AGIB and should be considered as a standard-of-care treatment. ClinicalTrials.gov (NCT01690585)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Objective: HY-088 injection is an ultrasmall superparamagnetic iron oxide nanoparticle (USPIOs) composed of iron oxide crystals coated with polyacrylic acid (PAA) on the surface. The purpose of this study was to investigate the pharmacokinetics, tissue distribution, and mass balance of HY-088 injection., Methods: The pharmacokinetics of [ 55 Fe]-HY-088 and [ 14 C]-HY-088 were investigated in 48 SD rats by intravenous injection of 8.5 (low-dose group), 25.5 (medium-dose group), and 85 (high-dose group) mg/100 μCi/kg. Tissue distribution was studied by intravenous injection of 35 mg/100 μCi/kg in 48 SD rats, and its tissue distribution in vivo was obtained by ex vivo tissue assay. At the same time, [ 14 C]-HY-088 was injected intravenously at a dose of 25.5 mg/100 μCi/kg into 16 SD rats, and its tissue distribution in vivo was studied by quantitative whole-body autoradiography. [ 14 C]-HY-088 and [ 55 Fe]-HY-088 were injected intravenously into 24 SD rats at a dose of 35 mg/100 μCi/kg, and their metabolism was observed., Results: In the pharmacokinetic study, [ 55 Fe]-HY-088 reached the maximum observed concentration (C max ) at 0.08 h in the low- and medium-dose groups of SD rats. [ 14 C]-HY-088 reached C max at 0.08 h in the three groups of SD rats. The area under the concentration-time curve (AUC) of [ 55 Fe]-HY-088 and [ 14 C]-HY-088 increased with increasing dose. In the tissue distribution study, [ 55 Fe]-HY-088 and [ 14 C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes of both female and male rats. In the mass balance study conducted over 57 days, the radioactive content of 55 Fe from [ 55 Fe]-HY-088 was primarily found in the carcass, accounting for 86.42 ± 4.18% in females and 95.46 ± 6.42% in males. The radioactive recovery rates of [ 14 C]-HY-088 in the urine of female and male rats were 52.99 ± 5.48% and 60.66 ± 2.23%, respectively., Conclusions: Following single intravenous administration of [ 55 Fe]-HY-088 and [ 14 C]-HY-088 in SD rats, rapid absorption was observed. Both [ 55 Fe]-HY-088 and [ 14 C]-HY-088 were primarily distributed in the liver, spleen, and lymph nodes. During metabolism, the radioactivity of [ 55 Fe]-HY-088 is mainly present in the carcass, whereas the 14 C-labeled [ 14 C]-HY-088 shell PAA is eliminated from the body mainly through the urine., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: This review summarizes the available data on the effectiveness of indocyanine green fluorescence imaging (ICG-FI) for real-time detection of breast cancer (BC) tumors with perioperative imaging technologies., Methods: PubMed and Scopus databases were exhaustively searched for publications on the use of the real-time ICG-FI evaluation of BC tumors with non-conventional breast imaging technologies., Results: Twenty-three studies were included in this review. ICG-FI has been used for BC tumor identification in 12 orthotopic animal tumor experiences, 4 studies on animal assessment, and for 7 human clinical applications. The BC tumor-to-background ratio (TBR) was 1.1-8.5 in orthotopic tumor models and 1.4-3.9 in animal experiences. The detection of primary human BC tumors varied from 40% to 100%. The mean TBR reported for human BC varied from 2.1 to 3.7. In two studies evaluating BC surgical margins, good sensitivity (93.3% and 100%) and specificity (60% and 96%) have been reported, with a negative predictive value of ICG-FI to predict margin involvement intraoperatively of 100% in one study., Conclusions: The use of ICG-FI as a guiding tool for the real-time identification of BC tumors and for the assessment of tumor boundaries is promising. There is great variability between the studies with regard to timing and dose. Further evidence is needed to assess whether ICG-guided BC surgery may be implemented as a standard of care., (© 2024. The Author(s).)