RESUMEN
Bacille Calmette-Guérin (BCG) vaccine has been used increasingly in immunotherapy, including treatment of non-muscle-invasive bladder cancer, as an adjuvant therapy in metastatic prostate cancer and metastatic melanoma. However, systemic infection from inadvertent intravenous (instead of intravesical) injection is uncommon and can have systemic ramifications. We encountered 3 patients with disseminated Mycobacterium bovis infection that ensued after intravenous BCG injection.
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Vacuna BCG , Mycobacterium bovis , Humanos , Vacuna BCG/efectos adversos , Vacuna BCG/administración & dosificación , Masculino , Mycobacterium bovis/aislamiento & purificación , Mycobacterium bovis/inmunología , Persona de Mediana Edad , Inyecciones Intravenosas , Tuberculosis/tratamiento farmacológico , Anciano , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
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.
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Modelos Animales de Enfermedad , Progresión de la Enfermedad , Sepsis , Animales , Sepsis/microbiología , Humanos , Ratones , Inyecciones IntravenosasRESUMEN
Many disorders affect multiple organs or involve different regions of the body, so it is critical to deliver therapeutics systemically to target the affected cells located in different sites. Intravenous injection is a widely used systemic delivery route in preclinical studies that assess treatments intended for body-wide administration. In adult mice, it involves the intravenous administration of the therapeutic agent into the mouse's lateral tail veins. When mastered, tail-vein injections are safe and fast, and only require simple and commonly available tools. However, tail-vein injections are technically challenging and require extensive training and continuous practice to ensure the accurate delivery of the intended dose. Here we describe a detailed, optimized, lateral tail-vein injection protocol that we have developed based on our experience and on recommendations that had been previously reported by other groups. Other than the mouse restrainers and insulin syringes, this protocol requires only reagents and equipment that are readily available in most labs. We found that following this protocol results in consistently successful intravenous delivery of adeno-associated virus (AAV) into the tail veins of unsedated 7-9 week-old mice. Additionally, we describe the optimized protocols for the histological detection of fluorescent reporter proteins and vector genome per diploid genome (vg/dg) quantification used to assess AAV transduction and biodistribution. The goal of this protocol is to aid experimenters in easily performing tail-vein injections successfully and consistently, which can reduce the practice time needed to master the technique.
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Dependovirus , Cola (estructura animal) , Animales , Ratones , Dependovirus/genética , Inyecciones Intravenosas , Vectores Genéticos/administración & dosificaciónRESUMEN
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 (18F-flurodeoxyglucose [FDG]); (2) peptide-based probe measuring angiogenesis (64Cu-NOTA-PEG4-cRGD2); and (3) dextran-based nanocarrier (64Cu-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.
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Venas Yugulares , Neoplasias de la Próstata , Radiofármacos , Animales , Ratones , Masculino , Venas Yugulares/diagnóstico por imagen , Venas Yugulares/metabolismo , Distribución Tisular , Radiofármacos/farmacocinética , Radiofármacos/administración & dosificación , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Tomografía de Emisión de Positrones/métodos , Inyecciones Intravenosas , Línea Celular TumoralRESUMEN
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.
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Heparina , Neoplasias , Subtilisinas , Trombosis , Animales , Subtilisinas/administración & dosificación , Ratones , Trombosis/tratamiento farmacológico , Inyecciones Intravenosas , Heparina/administración & dosificación , Neoplasias/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Fibrinolíticos/farmacología , Electricidad Estática , Cobayas , Masculino , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Liposomas , HumanosRESUMEN
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.
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Anticuerpos Monoclonales Humanizados , Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma Basocelular/tratamiento farmacológico , Antineoplásicos Inmunológicos/administración & dosificación , Antineoplásicos Inmunológicos/efectos adversos , Antineoplásicos Inmunológicos/uso terapéutico , Inyecciones Intravenosas , Femenino , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVE: Recombinant adeno-associated virus (rAAV) vectors are powerful tools for the sustained expression of proteins in vivo and have been successfully used for mechanistic studies in mice. A major challenge associated with this method is to obtain tissue specificity and high expression levels without need of local virus administration. METHODS: To achieve this goal for brown adipose tissue (BAT), we developed a rAAV vector for intravenous bolus injection, which includes an expression cassette comprising an uncoupling protein-1 enhancer-promoter for transcription in brown adipocytes and miR122 target sequences for suppression of expression in the liver, combined with packaging in serotype Rec2 capsid protein. To test tissue specificity, we used a version of this vector expressing Cre recombinase to transduce mice with floxed alleles to knock out MLXIPL (ChREBP) or tdTomato-Cre reporter mice. RESULTS: We demonstrated efficient Cre-dependent recombination in interscapular BAT and variable effects in minor BAT depots, but little or no efficacy in white adipose tissues, liver and other organs. Direct overexpression of glucose transporter SLC2A1 (GLUT1) using the rAAV vector in wild type mice resulted in increased glucose uptake and glucose-dependent gene expression in BAT, indicating usefulness of this vector to increase the function even of abundant proteins. CONCLUSION: Taken together, we describe a novel brown adipocyte-specific rAAV method to express proteins for loss-of-function and gain-of-function metabolic studies. The approach will enable researchers to access brown fat swiftly, reduce animal breeding time and costs, as well as enable the creation of new transgenic mouse models combining multiple transgenes.
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Adipocitos Marrones , Tejido Adiposo Pardo , Dependovirus , Vectores Genéticos , Animales , Ratones , Dependovirus/genética , Dependovirus/metabolismo , Vectores Genéticos/genética , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Ratones Endogámicos C57BL , Inyecciones Intravenosas , Masculino , Serogrupo , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Integrasas/metabolismo , Integrasas/genéticaRESUMEN
OBJECTIVE: To determine the pharmacokinetics and physiological effects following oral and intravenous (IV) administration of gabapentin in goats. STUDY DESIGN: Prospective, crossover study with a 3 week washout period between treatments. ANIMALS: A total of eight healthy, client-owned, female goats. METHODS: Gabapentin (10 mg kg-1) was administered to goats either orally or IV. Gabapentin concentrations were measured in serum samples collected 0-96 hours post-administration using liquid chromatography-quadrupole time-of-flight mass spectrometry. Heart rate, respiratory rate, blood pressure and temperature were recorded before and throughout the study. Correlations of the mean serum concentrations of gabapentin to those of each physiological parameter were determined using the Pearson method. RESULTS: The mean and standard deviation of oral bioavailability for gabapentin was 60.9 ± 11.2%. Maximum serum concentration of gabapentin was lower following oral (1.19 ± 0.29 µg mL-1) than after IV administration (59.76 ± 14.38 µg mL-1, p < 0.0001). Half-lives were longer following PO (8.18 ± 0.57 hours) than after IV administration (1.79 ± 0.06 hours, p < 0.0001). Time to maximum concentration was 6.86 ± 2.27 hours following oral administration. Heart rate was inversely correlated with serum gabapentin concentrations. Slight ataxia was observed in three animals, and one became recumbent following IV gabapentin. CONCLUSIONS AND CLINICAL RELEVANCE: Gabapentin is well-absorbed following oral administration to goats but yielded significantly lower serum concentrations than the IV route. The longer half-life of gabapentin following oral than after IV administration may result from prolonged absorption throughout the caprine gastrointestinal tract. IV gabapentin may cause slight ataxia in some goats.
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Estudios Cruzados , Gabapentina , Cabras , Animales , Gabapentina/administración & dosificación , Gabapentina/farmacocinética , Femenino , Administración Oral , Inyecciones Intravenosas/veterinaria , Analgésicos/farmacocinética , Analgésicos/administración & dosificación , Semivida , Frecuencia Cardíaca/efectos de los fármacos , Estudios Prospectivos , Administración Intravenosa/veterinariaRESUMEN
BACKGROUND: The aim of this study was to evaluate the adverse effects of allogeneic mesenchymal stem cells (MSCs) transplanted via intravenous infusion in dogs and examine their safety. We performed a retrospective analysis of various clinical assessments, including physical examination, blood tests, and radiographs, and monitored the formation of neoplasms during a 6-month follow-up period in 40 client-owned dogs that received intravenous infusion of adipose tissue-derived MSCs (AT-MSCs) for the treatment of various underlying diseases between 2012 and 2018. RESULTS: No significant adverse effects of MSC therapy were detected by clinical assessment, blood tests, or radiographic examination in the 6-month follow-up period after the first MSC treatment. Additionally no new neoplasms were observed during this period. CONCLUSIONS: To our knowledge, this study is the first to evaluate the safety aspects (≥ 6 months) associated with intravenous allogeneic AT-MSC infusion. These results suggest that allogenic AT-MSC infusion could be a useful and relatively safe therapeutic approach in canines.
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Enfermedades de los Perros , Trasplante de Células Madre Mesenquimatosas , Animales , Perros , Trasplante de Células Madre Mesenquimatosas/veterinaria , Trasplante de Células Madre Mesenquimatosas/efectos adversos , Trasplante de Células Madre Mesenquimatosas/métodos , Femenino , Masculino , Estudios Retrospectivos , Enfermedades de los Perros/terapia , Células Madre Mesenquimatosas , Trasplante Homólogo/veterinaria , Inyecciones Intravenosas/veterinaria , Tejido Adiposo/citologíaRESUMEN
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.
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Incompatibilidad de Medicamentos , Nafcilina , Ondansetrón , Ondansetrón/administración & dosificación , Ondansetrón/química , Nafcilina/administración & dosificación , Nafcilina/química , Infusiones Intravenosas , Administración Intravenosa , Estabilidad de Medicamentos , Concentración de Iones de Hidrógeno , Antieméticos/administración & dosificación , Antieméticos/química , Inyecciones IntravenosasRESUMEN
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.
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Dependovirus , Terapia Genética , Mucopolisacaridosis III , Retina , Animales , Mucopolisacaridosis III/terapia , Mucopolisacaridosis III/genética , Terapia Genética/métodos , Dependovirus/genética , Retina/patología , Ratones , Modelos Animales de Enfermedad , Hidrolasas/genética , Animales Recién Nacidos , Ratones Endogámicos C57BL , Demencia/genética , Demencia/terapia , Vectores Genéticos/administración & dosificación , Inyecciones IntravenosasRESUMEN
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.
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Antineoplásicos , Cobre , Metformina , Nanopartículas , Polímeros , Metformina/química , Metformina/farmacología , Metformina/administración & dosificación , Nanopartículas/química , Animales , Cobre/química , Ratones , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/administración & dosificación , Polímeros/química , Humanos , Inyecciones Intravenosas , Tamaño de la Partícula , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Línea Celular TumoralRESUMEN
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.
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Ensayo de Inmunoadsorción Enzimática , Factor de Crecimiento de Hepatocito , Proteínas Recombinantes , Animales , Ensayo de Inmunoadsorción Enzimática/métodos , Masculino , Ratas , Femenino , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/administración & dosificación , Humanos , Factor de Crecimiento de Hepatocito/farmacocinética , Factor de Crecimiento de Hepatocito/sangre , Ratas Sprague-Dawley , Macaca fascicularis , Inyecciones Intravenosas , Relación Dosis-Respuesta a Droga , Reproducibilidad de los Resultados , Administración IntravenosaRESUMEN
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.
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Compuestos de Aluminio , Cardiotoxicidad , Mitocondrias Cardíacas , Estrés Oxidativo , Fosfinas , Ratas Wistar , Animales , Fosfinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Masculino , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/efectos de los fármacos , Mitocondrias Cardíacas/patología , Compuestos de Aluminio/toxicidad , Modelos Animales de Enfermedad , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Inyecciones Intravenosas , Especies Reactivas de Oxígeno/metabolismo , Ratas , Antioxidantes/farmacología , Factores de TiempoRESUMEN
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.
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Ingle , Procedimientos de Cirugía Plástica , Colgajos Quirúrgicos , Procedimientos Quirúrgicos Vasculares , Humanos , Femenino , Masculino , Ingle/irrigación sanguínea , Persona de Mediana Edad , Anciano , Procedimientos Quirúrgicos Vasculares/efectos adversos , Procedimientos Quirúrgicos Vasculares/mortalidad , Colgajos Quirúrgicos/efectos adversos , Procedimientos de Cirugía Plástica/efectos adversos , Estudios Retrospectivos , Italia , Amputación Quirúrgica , Cicatrización de Heridas , Inyecciones Intravenosas , Resultado del Tratamiento , Factores de Tiempo , Abuso de Sustancias por Vía Intravenosa/complicaciones , Factores de Riesgo , Recuperación del Miembro , Infección de la Herida QuirúrgicaRESUMEN
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.
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Infusiones Intraóseas , Paro Cardíaco Extrahospitalario , Humanos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/mortalidad , Femenino , Masculino , Infusiones Intraóseas/métodos , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Taiwán/epidemiología , Servicios Médicos de Urgencia/métodos , Extremidad Superior , COVID-19 , Resultado del Tratamiento , Reanimación Cardiopulmonar/métodos , Adulto Joven , Inyecciones Intravenosas , SARS-CoV-2RESUMEN
BACKGROUND: Although research on the mechanism and control of pain and inflammation in fish has increased in recent years, the use of analgesic drugs is limited due to the lack of pharmacological information about analgesic drugs. Tolfenamic acid is a non-steroidal anti-inflammatory drug and can be used in fish due to its low side effect profile and superior pharmacokinetic properties. OBJECTIVES: The pharmacokinetics, bioavailability and plasma protein binding of tolfenamic acid were investigated following single intravascular (IV), intramuscular (IM) and oral administration of 2 mg/kg in rainbow trout at 13 ± 0.5°C. METHODS: The experiment was carried out on a total of 234 rainbow trout (Oncorhynchus mykiss). Tolfenamic acid was administered to fish via IV, IM and oral route at a dose of 2 mg/kg. Blood samples were taken at 13 different sampling times until the 72 h after drug administration. The plasma concentrations of tolfenamic acid were quantified using high pressure liquid chromatography-ultraviolet (UV) and pharmacokinetic parameters were assessed using non-compartmental analysis. RESULTS: The elimination half-life (t1/2Êz) of tolfenamic acid for IV, IM and oral routes was 3.47, 6.75 and 9.19 h, respectively. For the IV route, the volume of distribution at a steady state and total body clearance of tolfenamic acid were 0.09 L/kg and 0.03 L/h/kg, respectively. The peak plasma concentration and bioavailability for IM and oral administration were 8.82 and 1.24 µg/mL, and 78.45% and 21.48%, respectively. The mean plasma protein binding ratio of tolfenamic acid in rainbow trout was 99.48% and was not concentration dependent. CONCLUSIONS: While IM route, which exhibits both the high plasma concentration and bioavailability, can be used in rainbow trout, oral route is not recommended due to low plasma concentration and bioavailability. However, there is a need to demonstrate the pharmacodynamic activity of tolfenamic acid in rainbow trout.
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Antiinflamatorios no Esteroideos , Disponibilidad Biológica , Proteínas Sanguíneas , Oncorhynchus mykiss , ortoaminobenzoatos , Animales , Oncorhynchus mykiss/metabolismo , Oncorhynchus mykiss/sangre , ortoaminobenzoatos/farmacocinética , ortoaminobenzoatos/sangre , Antiinflamatorios no Esteroideos/farmacocinética , Antiinflamatorios no Esteroideos/sangre , Administración Oral , Proteínas Sanguíneas/metabolismo , Inyecciones Intramusculares/veterinaria , Unión Proteica , Inyecciones Intravenosas/veterinaria , SemividaRESUMEN
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 .
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Glucemia , Dexametasona , Humanos , Dexametasona/administración & dosificación , Método Doble Ciego , Masculino , Femenino , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Persona de Mediana Edad , Anciano , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/sangre , Inyecciones Intravenosas , Periodo Posoperatorio , Artroplastia de Reemplazo de Cadera/efectos adversos , Glucocorticoides/administración & dosificación , Artroplastia de Reemplazo/efectos adversos , Administración IntravenosaRESUMEN
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.
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Intoxicación por Mercurio , Mercurio , Humanos , Intoxicación por Mercurio/tratamiento farmacológico , Inyecciones Intravenosas , Masculino , Insuficiencia Multiorgánica/inducido químicamente , AdultoRESUMEN
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.