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In a trial involving adults with out-of-hospital cardiac arrest, an intraosseous-first strategy for vascular access did not result in a higher incidence of 30-day survival than an intravenous-first strategy.

Background Indications for intra-osseous (IO) infusion are increasing in adults requiring administration of fluids and medications during initial resuscitation. However, this route is rarely used nowadays due to a lack of knowlegde and training. We reviewed the current evidence for its use in adults requiring resuscitative procedures, the contraindications of the technique, and modalities for catheter implementation and skill acquisition. Methods A PubMed search for all articles published up to December 2015 was performed by using the terms “Intra-osseous” AND “Adult”. Additional articles were included by using the “related citations” feature of PubMed or checking references of selected articles. Editorials, comments and case reports were excluded. Abstracts of all the articles that the search yielded were independently screened for eligibility by two authors and included in the analysis after mutual consensus. In total, 84 full-text articles were reviewed and 49 of these were useful for answering the following question “when, how, and for which population should an IO infusion be used in adults” were selected to prepare independent drafts. Once this step had been completed, all authors met, reviewed the drafts together, resolved disagreements by consensus with all the authors, and decided on the final version. Results IO infusion should be implemented in all critical situations when peripheral venous access is not easily obtainable. Contraindications are few and complications are uncommon, most of the time bound to prolonged use. The IO infusion allows for blood sampling and administration of virtually all types of fluids and medications including vasopressors, with a bioavailability close to the intravenous route. Unfortunately, IO infusion remains underused in adults even though learning the technique is rapid and easy. Conclusions Indications for IO infusion use in adults requiring urgent parenteral access and having difficult intravenous access are increasing. Physicians working in emergency departments or intensive care units should learn the procedures for catheter insertion and maintenance, the contraindications of the technique, and the possibilities this access offers.

Intravenous vascular access is technically challenging in the adult mouse and even more challenging in neonatal mice. The authors describe the technique of retro-orbital injection of the venous sinus in the adult and neonatal mouse. This technique is a useful alternative to tail vein injection for the administration of non-tumorigenic compounds. The authors report that they have routinely used this technique in the adult mouse to administer volumes up to 150 μl without incident. Administration of retro-orbital injections is more challenging in neonatal mice but can reliably deliver volumes up to 10 μl.

Our goal is to develop a vaccine that sustainably prevents Plasmodium falciparum (Pf) malaria in ≥80% of recipients. Pf sporozoites (PfSPZ) administered by mosquito bites are the only immunogens shown to induce such protection in humans. Such protection is thought to be mediated by CD8⁺ T cells in the liver that secrete interferon-γ (IFN-γ). We report that purified irradiated PfSPZ administered to 80 volunteers by needle inoculation in the skin was safe, but suboptimally immunogenic and protective. Animal studies demonstrated that intravenous immunization was critical for inducing a high frequency of PfSPZ-specific CD8⁺, IFN-γ-producing T cells in the liver (nonhuman primates, mice) and conferring protection (mice). Our results suggest that intravenous administration of this vaccine will lead to the prevention of infection with Pf malaria.

Consistent high-level, vaccine-induced protection against human malaria has only been achieved by inoculation of Plasmodium falciparum (Pf) sporozoites (SPZ) by mosquito bites. We report that the PfSPZ Vaccine—composed of attenuated, aseptic, purified, cryopreserved PfSPZ—was safe and well tolerated when administered four to six times intravenously (IV) to 40 adults. Zero of six subjects receiving five doses and three of nine subjects receiving four doses of 1.35 × 10⁵ PfSPZ Vaccine and five of six nonvaccinated controls developed malaria after controlled human malaria infection (P = 0.015 in the five-dose group and P = 0.028 for overall, both versus controls). PfSPZ-specific antibody and T cell responses were dose-dependent. These data indicate that there is a dose-dependent immunological threshold for establishing high-level protection against malaria that can be achieved with IV administration of a vaccine that is safe and meets regulatory standards.

GK-1 is a safe and effective molecule with high antimetastatic activity against murine breast and skin cancer. GK-1 treatment enhances cytotoxic response of CD8+ lymphocytes against the tumor and modifies the oxidative stress in the tumor. This study was designed to compare the antitumor efficacy of GK-1 by subcutaneous (SC) versus intravenous (IV) route of administration in the 4T1 mouse mammary carcinoma model and to extend its innocuity in heart and kidney, key tissues for observing damage induced by anticancer drugs and immunotherapy. BALB/c female mice were injected orthotopically with 1000 4T1 cells. When palpable primary tumors of about 1 mm3 were detected, GK-1 (5 mg/kg) was administered IV or SC weekly for 21 days. Tumor growth and mouse weight were monitored weekly. The primary tumor weight and volume, the number of lung metastases, and programmed cell death protein 1 (PD-1) expression were recorded after 28 days of starting treatment. Kidney, heart, spleen, serum, and blood samples from naïve mice were obtained to evaluate the safety of GK-1 administration by measuring the degree of damage to these tissues with specific cytotoxic markers. Subcutaneous or intravenous administration of GK-1 significantly increased the lifespan of mice and significantly reduced the primary tumor weight and volume and the number of lungs macrometastases. GK-1 reduced the expression of PD-1 in tumor-infiltrating lymphocytes in mice regardless of the route of immunization used, which is especially encouraging. No evidence of damage to kidney or heart tissues was detected in the tumor-free mice. This study supports that subcutaneous GK-1 administered, has an efficacy non-inferior to intravenous administration, well-tolerated with a similar safety profile and therefore offers a less invasive valid treatment alternative. •The subcutaneous and intravenous treatment of GK-1 had equal antitumoral effect in a breast cancer model.•GK-1 treatment reduces the expression of PD-1 on tumor infiltrating lymphocytes.•GK-1 is not immunogenic; therefore, it does not cause antibody immune-mediated adverse effects such as renal or cardiac damage in tumor-free mice.•GK-1 does not increase reactive oxygen species in tumor-free mice.

Intracoronary administration of an abciximab bolus during a primary percutaneous coronary intervention results in a high local drug concentration, improved perfusion, and reduction of infarct size compared with intravenous bolus application. However, the safety and efficacy of intracoronary versus standard intravenous bolus application in patients with ST-elevation myocardial infarction (STEMI) undergoing this intervention has not been tested in a large-scale clinical trial. The AIDA STEMI trial was a randomised, open-label, multicentre trial. Patients presenting with STEMI in the previous 12 h with no contraindications for abciximab were randomly assigned in a 1:1 ratio by a central web-based randomisation system to intracoronary versus intravenous abciximab bolus (0·25 mg/kg bodyweight) during percutaneous coronary intervention with a subsequent 12 h intravenous infusion 0·125 μg/kg per min (maximum 10 μg/min). The primary endpoint was a composite of all-cause mortality, recurrent infarction, or new congestive heart failure within 90 days of randomisation. Secondary endpoints were the time to occurrence of the primary endpoint, each individual component of that endpoint, early ST-segment resolution, thrombolysis in myocardial infarction (TIMI) flow grade, and enzymatic infarct size. A masked central committee adjudicated the primary outcome and its components. Treatment allocation was not concealed from patients and investigators. This trial is registered with ClinicalTrials.gov, NCT00712101. Between July, 2008, and April, 2011, 2065 patients were randomly assigned intracoronary abciximab (n=1032) or intravenous abciximab (n=1033). Intracoronary, as compared with intravenous abciximab, resulted in a similar rate of the primary composite clinical endpoint at 90 days in 1876 analysable patients (7·0% vs 7·6%; odds ratio [OR] 0·91; 95% CI 0·64–1·28; p=0·58). The incidence of death (4·5% vs 3·6%; 1·24; 0·78–1·97; p=0·36) and reinfarction (1·8% vs 1·8%; 1·0; 0·51–1·96; p=0·99) did not differ between the treatment groups, whereas less patients in the intracoronary group had new congestive heart failure (2·4% vs 4·1%; 0·57; 0·33–0·97; p=0·04). None of the secondary endpoints or safety measures differed significantly between groups. In patients with STEMI undergoing primary percutaneous coronary intervention, intracoronary as compared to intravenous abciximab did not result in a difference in the combined endpoint of death, reinfarction, or congestive heart failure. Since intracoronary abciximab bolus administration is safe and might be related to reduced rates of congestive heart failure the intracoronary route might be preferred if abciximab is indicated. Lilly, Germany. University of Leipzig—Heart Centre. University of Leipzig, Clinical Trial Centre Leipzig, supported by the Federal Ministry of Education and Research (BMBF).

Carbon nanotubes are promising new materials for molecular delivery in biological systems. The long-term fate of nanotubes intravenously injected into animals in vivo is currently unknown, an issue critical to potential clinical applications of these materials. Here, using the intrinsic Raman spectroscopic signatures of single-walled carbon nanotubes (SWNTs), we measured the blood circulation of intravenously injected SWNTs and detect SWNTs in various organs and tissues of mice ex vivo over a period of three months. Functionalization of SWNTs by branched polyethylene-glycol (PEG) chains was developed, enabling thus far the longest SWNT blood circulation up to 1 day, relatively low uptake in the reticuloendothelial system (RES), and near-complete clearance from the main organs in [almost equal to]2 months. Raman spectroscopy detected SWNT in the intestine, feces, kidney, and bladder of mice, suggesting excretion and clearance of SWNTs from mice via the biliary and renal pathways. No toxic side effect of SWNTs to mice was observed in necropsy, histology, and blood chemistry measurements. These findings pave the way to future biomedical applications of carbon nanotubes.

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.

Decongestion is a primary goal during hospitalizations for decompensated heart failure (HF). However, data surrounding the preferred route and strategy of diuretic administration are limited with varying results in prior studies. This is a retrospective analysis using patients from ASCEND-HF with a stable diuretic strategy in the first 24 hours following randomization. Patients were divided into three groups: intravenous (IV) continuous, IV bolus and oral strategy. Baseline characteristics, in-hospital outcomes, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality were compared across groups. Inverse propensity weighted modeling was used for adjustment. Among 5,738 patients with a stable diuretic regimen in the first 24 hours (80% of overall ASCEND trial), 3,944 (68.7%) patients received IV intermittent bolus administration of diuretics, 799 (13.9%) patients received IV continuous therapy and 995 (17.3%) patients with oral administration. Patients in the IV continuous group had a higher baseline creatinine (IV continuous 1.4 [1.1-1.7]; intermittent bolus 1.2 [1.0-1.6]; oral 1.2 [1.0-1.4] mg/dL; P <0.001) and high NTproBNP (IV continuous 5,216 [2,599-11,603]; intermittent bolus 4,944 [2,339-9,970]; oral 3,344 [1,570-7,077] pg/mL; P <0.001). There was no difference between IV continuous and intermittent bolus group in weight change, total urine output and change in renal function till 10 days/discharge (adjusted P >0.05 for all). There was no difference in 30 day mortality and HF readmission (adjusted OR 1.08 [95%CI: 0.74, 1.57]; P = 0.701) and 180 days mortality (adjusted OR 1.04 [95%CI: 0.75, 1.43]; P = 0.832). In a large cohort of patients with decompensated HF, there were no significant differences in diuretic-related in-hospital, or post-discharge outcomes between IV continuous and intermittent bolus administration. Tailoring appropriate diuretic strategy to different states of acute HF and congestion phenotypes needs to be further investigated.