Mechanisms of triple-negative breast cancer extravasation: Impact of the physical environment and endothelial glycocalyx.

Cancer metastasis is the leading cause of death for those afflicted with cancer. In cancer metastasis, the cancer cells break off from the primary tumor, penetrate nearby blood vessels, and attach and extravasate out of the vessels to form secondary tumors at distant organs. This makes extravasation a critical step of the metastatic cascade. Herein, with a focus on triple-negative breast cancer, the role that the prospective secondary tumor microenvironment's mechanical properties play in circulating tumor cells' extravasation is reviewed. Specifically, the effects of the physically regulated vascular endothelial glycocalyx barrier element, vascular flow factors, and subendothelial extracellular matrix mechanical properties on cancer cell extravasation are examined. The ultimate goal of this review is to clarify the physical mechanisms that drive triple-negative breast cancer extravasation, as these mechanisms may be potential new targets for anti-metastasis therapy.

Reciprocal Interaction with Neutrophils Facilitates Cutaneous Accumulation of Liposomes.

Liposomes are versatile drug delivery systems in clinical use for cancer and many other diseases. Unfortunately, PEGylated liposomal doxorubicin (sLip/DOX) exhibits serious dose-limiting cutaneous toxicities, which are closely related to the extravascular accumulation of sLip/DOX in the dermis. No clinical interventions have been proposed for cutaneous toxicities due to the elusive transport pathways. Herein, we showed that the reciprocal interaction between liposomes and neutrophils played pivotal roles in liposome extravasation into the dermis. Neutrophils captured liposomes via the complement receptor 3 (CD11b/CD18) recognizing the fragment of complement component C3 (iC3b) deposited on the liposomal surface. Uptake of liposomes also activated neutrophils to induce CD11b upregulation and enhanced the ability of neutrophils to migrate outside the capillaries. Furthermore, inhibition of complement activation either by CRIg-L-FH (a C3b/iC3b targeted complement inhibitor) or blocking the phosphate negative charge in mPEG-DSPE could significantly reduce liposome uptake by neutrophils and alleviate the cutaneous accumulation of liposomes. These results validated the liposome extravasation pathway mediated by neutrophils and provided potential solutions to the devastating cutaneous toxicities occurring during sLip/DOX treatment.

The effects of temperament type on infusion extravasation in newborns.

Infusion extravasation has an increased incidence in newborns, which can result in various adverse outcomes. This study aimed to investigate the effects of different types of temperament on infusion extravasation in newborns. A total of 209 newborns aged 4-7 days who were treated with infusion therapy were assessed for temperament type using the neonatal behavioral assessment scale score (NBAS). The 2009 Infusion Nurses Society clinical grading criteria for extravasation were used, and the clinical data of the newborns, such as gestational age and body weight, were collected. Out of 209 newborns assessed, 107 developed infusion extravasations, with an incidence rate of 51.2%. Newborns with intermediate temperament type were more prone to develop infusion extravasation. Newborns with low body weight, amniotic fluid aspiration syndrome, or meconium aspiration syndrome were prone to develop infusion extravasation. Body weight, temperament type of consolability, temperament type of peak of excitement, diseases, general temperament type, and NBAS total scores of the neonates were independent risk factors for infusion extravasation. Thus, different types of temperament can have an impact on neonatal extravasation.

Conditions that promote transcellular neutrophil migration in vivo.

Circulating leukocytes enter tissue either through endothelial junctions (paracellular) or via a pore through the body of endothelial cells (transcellular). We have previously shown that genetically replacing VE-cadherin with a VE-cadherin-α-catenin (VEC-αC) fusion construct-which binds constitutively to actin-obstructs junctions, and blocks leukocyte extravasation in lung, skin and postcapillary venules of cremaster muscle. However, neutrophil recruitment into the inflamed peritoneal cavity was unimpaired. Investigating reasons for this, here, we visualized neutrophil diapedesis by 3D intravital video microscopy in the cremaster muscle and omentum, the major site of neutrophil recruitment into the peritoneal cavity. We found that 80% of neutrophil-extravasation occurred through HEVs in the omentum, which was unimpaired by VEC-αC. In addition, in larger venules (60-85 µm) of both tissues, less than 15% of neutrophils extravasated transcellularly in WT mice. However, in VEC-α-C mice, transcellular diapedesis increased severalfold in the omentum, but not in the cremaster. In line with this, omental venules expressed higher levels of ICAM-1 and atypical chemokine receptor 1. Furthermore, only in the omentum, VEC-αC expression caused reduced elongation of venular endothelium in flow-direction, suggesting different biomechanical properties. Collectively, VEC-αC does not inhibit paracellular transmigration in all types of venules and can modulate the diapedesis route.

Describing Intravenous Extravasation Injuries in Children (DIVE2 Study).

Background: Extravasation is the erroneous delivery of IV medication or fluid into the extravascular space. Complications ranging from mild injury to amputation can result, depending on the physical and pharmacologic properties of the infusate. Children are at increased risk for extravasation injuries. There is a paucity of data on the treatment and outcomes of extravasation injuries, particularly in terms of the role of pharmacologic antidotes. Objectives: To describe the incidence of extravasation at a tertiary pediatric care centre (as an update to a previous study), to identify the agents most commonly involved in extravasation injuries, to describe the antidotes used for management of injuries and their related adverse drug effects, and to describe complications related to injuries. Methods: The medical records of pediatric patients who experienced an extravasation injury at the BC Children's and BC Women's Hospitals, between September 1, 2008, and September 30, 2020, were reviewed. Data regarding management (adherence with institutional protocol) and outcomes of injuries were collected. Results: The 242 charts included in the analysis noted a total of 245 extravasation injuries, for an extravasation incidence of 0.04% per patient-day. Of the 242 patients, 110 were excluded from secondary outcome analysis due to lack of data detailing the extravasation event. Of the remaining 132 patients, the majority were neonates (n = 54, 40.9%), infants (n = 33, 25.0%), and children (n = 34, 25.8%), and more than a third were treated on general pediatric wards (n = 50, 37.9%). The medications most frequently involved were total parenteral nutrition with lipids (36/132, 27.3%), vancomycin (36/132, 27.3%), and IV fluids (35/132, 26.5%). Most of the patients had mild outcomes and recovered without complications. No adverse drug events from antidotes were reported. Conclusions: The incidence of extravasation at the study institution remained low, with the medications involved being similar to those reported in the literature and the majority of patients having mild outcomes. Additional prospective studies are needed to assess the efficacy and safety of antidotes administered for extravasation injuries.

Contexte: L'extravasation est l'administration erronée de médicaments ou de liquides IV dans l'espace extravasculaire. Des complications allant d'une blessure légère à l'amputation peuvent en résulter, en fonction des propriétés physiques et pharmacologiques de la perfusion. Les enfants courent un risque accru de blessures par extravasation. Il existe peu de données sur le traitement et les conséquences des blessures par extravasation, notamment en ce qui concerne le rôle des antidotes pharmacologiques. Objectifs: Décrire l'incidence des extravasations dans un centre de soins pédiatriques tertiaires (en tant que mise à jour d'une étude précédente), recenser les agents les plus couramment impliqués dans les blessures par extravasation, décrire les antidotes utilisés pour la gestion des blessures et leurs effets indésirables liés aux médicaments et décrire les complications liées aux blessures. Méthodologie: Les dossiers médicaux des patients pédiatriques ayant subi une blessure par extravasation entre le 1er septembre 2008 et le 30 septembre 2020 aux hôpitaux BC Children's Hospital et BC Women's Hospital ont été examinés. Des données concernant la prise en charge (c'est-à-dire le respect du protocole de l'établissement) et les conséquences des blessures ont été recueillies. Résultats: Les 242 dossiers inclus dans l'analyse indiquaient un total de 245 blessures par extravasation, pour une incidence d'extravasation de 0,04 % par jour-patient. Parmi les 242 patients, 110 ont été exclus de l'analyse secondaire des conséquences en raison d'un manque de données concernant les détails de l'extravasation. Sur les 132 patients restants, la majorité était des nouveau-nés (n = 54, 40,9 %), des nourrissons (n = 33, 25,0 %) et des enfants (n = 34, 25,8 %) et plus du tiers ont reçu des soins dans un service de pédiatrie générale (n = 50, 37,9 %). Les médicaments les plus fréquemment impliqués étaient la nutrition parentérale totale avec des lipides (36/132, 27,3 %), la vancomycine (36/132, 27,3 %) et des liquides IV (35/132, 26,5 %). Les conséquences sur la plupart des patients étaient bénignes et ils se sont rétablis sans complications. Aucun effet indésirable lié aux antidotes n'a été signalé. Conclusions: L'incidence des extravasations dans l'établissement à l'étude est restée faible, les médicaments impliqués étant similaires à ceux rapportés dans la littérature et les conséquences pour la majorité des patients étaient bénignes. Des études prospectives supplémentaires sont nécessaires pour évaluer l'efficacité et la sécurité des antidotes administrés pour les blessures par extravasation.

Spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support: a case report.

BACKGROUND: Intercostal artery bleeding often occurs in a single vessel; in rare cases, it can occur in numerous vessels, making it more difficult to manage. CASE PRESENTATION: A 63-year-old Japanese man was admitted to the emergency department owing to sudden chest and back pain, dizziness, and nausea. Emergency coronary angiography revealed myocardial infarction secondary to right coronary artery occlusion. After intra-aortic balloon pumping, percutaneous coronary intervention was performed in the right coronary artery. At 12 hours following percutaneous coronary intervention, the patient developed new-onset left anterior chest pain and hypotension. Contrast-enhanced computed tomography revealed 15 sites of contrast extravasation within a massive left extrapleural hematoma. Emergency angiography revealed contrast leakage in the left 6th to 11th intercostal arteries; hence, transcatheter arterial embolization was performed. At 2 days after transcatheter arterial embolization, his blood pressure subsequently decreased, and contrast-enhanced computed tomography revealed the re-enlargement of extrapleural hematoma with multiple sites of contrast extravasation. Emergency surgery was performed owing to persistent bleeding. No active arterial hemorrhage was observed intraoperatively. Bleeding was observed in various areas of the chest wall, and an oxidized cellulose membrane was applied following ablation and hemostasis. The postoperative course was uneventful. CONCLUSION: We report a case of spontaneous intercostal artery bleeding occurring simultaneously in numerous vessels during antithrombotic therapy with mechanical circulatory support that was difficult to manage. As bleeding from numerous vessels may occur during antithrombotic therapy, even without trauma, appropriate treatments, such as transcatheter arterial embolization and surgery, should be selected in patients with such cases.

Delayed plasma kallikrein inhibition fosters post-stroke recovery by reducing thrombo-inflammation.

Activation of the kallikrein-kinin system promotes vascular leakage, inflammation, and neurodegeneration in ischemic stroke. Inhibition of plasma kallikrein (PK) - a key component of the KKS - in the acute phase of ischemic stroke has been reported to reduce thrombosis, inflammation, and damage to the blood-brain barrier. However, the role of PK during the recovery phase after cerebral ischemia is unknown. To this end, we evaluated the effect of subacute PK inhibition starting from day 3 on the recovery process after transient middle artery occlusion (tMCAO). Our study demonstrated a protective effect of PK inhibition by reducing infarct volume and improving functional outcome at day 7 after tMCAO. In addition, we observed reduced thrombus formation in cerebral microvessels, fewer infiltrated immune cells, and an improvement in blood-brain barrier integrity. This protective effect was facilitated by promoting tight junction reintegration, reducing detrimental matrix metalloproteinases, and upregulating regenerative angiogenic markers. Our findings suggest that PK inhibition in the subacute phase might be a promising approach to accelerate the post-stroke recovery process.

Required volume for color flow injection test to confirm the intravascular placement of a peripheral venous catheter.

BACKGROUND: Confirmation of adequate peripheral intravenous catheter placement is essential before using venous catheters. The color flow injection test has been reported as a method with high sensitivity and specificity for this purpose. The technique involves administrating saline through the peripheral venous route to observe changes in the color flow pattern around the same vein at a more central location. However, the required volume of saline remains uncertain. This study aims to determine the appropriate dosage for conducting the test in pediatric patients and explore any potential correlations between dosage and patient characteristics. METHODS: A prospective study was conducted in children under 6 years of age with American Society of Anesthesiologists Physical Status 1-2 presenting for general anesthesia. After an intravenous cannula was placed in the forearm under general anesthesia, normal saline was injected at a speed of approximately 1 mL/s while the axillary artery and vein were observed with color flow Doppler imaging. The volume of normal saline required to induce a change in the color flow pattern around the vessels was measured. Measurements were performed twice and averaged for comparison with patient characteristics and other factors. RESULTS: The study cohort included 30 patients aged from 0.3 to 5.5 (2.6 ± 1.6) years. The change in color flow Doppler imaging was noted in all the patients, and the average volume was 1.40 ± 0.36 mL (95% confidence interval (CI), 1.27-1.54; p < 0.001), which was significantly correlated with age, with a correlation coefficient of 0.435 (95% CI, 0.09-0.69; p = 0.02). CONCLUSIONS: The required volume for the color flow injection test is small; therefore, the test is easy to perform and minimally invasive in pediatric patients.

Acyclovir extravasation in a newborn: a case report.

OBJECTIVE: Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation. CASE REPORT: A female newborn (Iranian, Asian) with gestational age 37+2 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase. CONCLUSION: Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.

Pelvic fractures in blunt trauma patients: A comparative study.

BACKGROUND: Pelvic fractures (PF) with concomitant injuries are on the rise due to an increase of high-energy trauma. Increase of the elderly population with age related comorbidities further complicates the management. Abdominal organ injuries are kindred with PF due to the proximity to pelvic bones. Presence of contrast blush (CB) on computed tomography in patients with PF is considered a sign of active bleeding, however, its clinical significance and association with outcomes is debatable. AIM: To analyze polytrauma patients with PF with a focus on the geriatric population, co-injuries and the value of contrast blush. METHODS: This retrospective cohort study included 558 patients with PF admitted to level 1 trauma center (01/2017-01/2023). Analyzed variables included: Age, sex, mechanism of injury (MOI), injury severity score (ISS), Glasgow coma scale (GCS), abbreviated injury scale (AIS), co-injuries, transfusion requirements, pelvic angiography, embolization, laparotomy, orthopedic pelvic surgery, intensive care unit and hospital lengths of stay, discharge disposition and mortality. The study compared geriatric and non-geriatric patients, patients with and without CB and abdominal co-injuries. Propensity score matching was implemented in comparison groups. RESULTS: PF comprised 4% of all trauma admissions. 89 patients had CB. 286 (52%) patients had concomitant injuries including 93 (17%) patients with abdominal co-injuries. Geriatric patients compared to non-geriatric had more falls as MOI, lower ISS and AIS pelvis, higher GCS, less abdominal co-injuries, similar CB and angio-embolization rates, less orthopedic pelvic surgeries, shorter lengths of stay and higher mortality. After propensity matching, orthopedic pelvic surgery rates remained lower (8% vs 19%, P < 0.001), hospital length of stay shorter, and mortality higher (13% vs 4%, P < 0.001) in geriatric patients. Out of 89 patients with CB, 45 (51%) were embolized. After propensity matching, patients with CB compared to without CB had more pelvic angiography (71% vs 12%, P < 0.001), higher embolization rates (64% vs 22%, P = 0.02) and comparable mortality. CONCLUSION: Half of the patients with PF had concomitant co-injuries, including abdominal co-injuries in 17%. Similarly injured geriatric patients had higher mortality. Half of the patients with CB required an embolization.

Curvature-mediated rapid extravasation and penetration of nanoparticles against interstitial fluid pressure for improved drug delivery.

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine.

Modulation of angiopoietin-2 and Tie2: Organ specific effects of microvascular leakage and edema in mice.

INTRODUCTION: Critical illness is associated with organ failure, in which endothelial hyperpermeability and tissue edema play a major role. The endothelial angiopoietin/Tie2 system, a regulator of endothelial permeability, is dysbalanced during critical illness. Elevated circulating angiopoietin-2 and decreased Tie2 receptor levels are reported, but it remains unclear whether they cause edema independent of other critical illness-associated alterations. Therefore, we have studied the effect of angiopoietin-2 administration and/or reduced Tie2 expression on microvascular leakage and edema under normal conditions. METHODS: Transgenic male mice with partial deletion of Tie2 (heterozygous exon 9 deletion, Tie2+/-) and wild-type controls (Tie2+/+) received 24 or 72 pg/g angiopoietin-2 or PBS as control (n = 12 per group) intravenously. Microvascular leakage and edema were determined by Evans blue dye (EBD) extravasation and wet-to-dry weight ratio, respectively, in lungs and kidneys. Expression of molecules related to endothelial angiopoietin/Tie2 signaling were determined by ELISA and RT-qPCR. RESULTS: In Tie2+/+ mice, angiopoietin-2 administration increased EBD extravasation (154 %, p < 0.05) and wet-to-dry weight ratio (133 %, p < 0.01) in lungs, but not in the kidney compared to PBS. Tie2+/- mice had higher pulmonary (143 %, p < 0.001), but not renal EBD extravasation, compared to wild-type control mice, whereas a more pronounced wet-to-dry weight ratio was observed in lungs (155 %, p < 0.0001), in contrast to a minor higher wet-to-dry weight ratio in kidneys (106 %, p < 0.05). Angiopoietin-2 administration to Tie2+/- mice did not further increase pulmonary EBD extravasation, pulmonary wet-to-dry weight ratio, or renal wet-to-dry weight ratio. Interestingly, angiopoietin-2 administration resulted in an increased renal EBD extravasation in Tie2+/- mice compared to Tie2+/- mice receiving PBS. Both angiopoietin-2 administration and partial deletion of Tie2 did not affect circulating angiopoietin-1, soluble Tie2, VEGF and NGAL as well as gene expression of angiopoietin-1, -2, Tie1, VE-PTP, ELF-1, Ets-1, KLF2, GATA3, MMP14, Runx1, VE-cadherin, VEGFα and NGAL, except for gene and protein expression of Tie2, which was decreased in Tie2+/- mice compared to Tie2+/+ mice. CONCLUSIONS: In mice, the microvasculature of the lungs is more vulnerable to angiopoietin-2 and partial deletion of Tie2 compared to those in the kidneys with respect to microvascular leakage and edema.

Safe administration of noradrenaline by the peripheral route: A systematic review. / Administración segura de noradrenalina por vía periférica: una revisión sistemática.

PURPOSE: To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety. METHODS: Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included. RESULTS: NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA. CONCLUSIONS: Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

Evaluation of the clinical impact of decreasing the maximum osmolarity of neonatal peripheral parenteral nutrition.

OBJECTIVE: To describe the clinical impact of lowering the peripheral parenteral nutrition (PPN) maximum osmolarity limit from 1000 to 900 mOsm/L in patients in two neonatal intensive care units (NICUs). METHODS: This was a retrospective cohort study including inborn neonates that received PPN for at least 3 consecutive days within the first 14 days of life. Data were evaluated to compare the ability of PPN with a maximum osmolarity limit of 1000 to 900 mOsm/L to provide daily recommended macronutrient doses, and daily recommended goal calories, as well as to compare the incidence of significant peripheral intravenous (PIV) infiltrates. RESULTS: A total of 200 PPN orders representing 57 patients were included for analysis, with 100 PPN orders in each osmolarity cohort. Baseline characteristics were similar between the two cohorts. Significantly more PPN orders met goal amino acid doses (45% vs. 24%, p = 0.003) and goal intravenous fat emulsion (IVFE) doses (61% vs. 37%, p = 0.001) in the 1000 mOsm/L osmolarity limit cohort compared to the 900 mOsm/L osmolarity limit cohort. A total of three patients received hyaluronidase for PN infiltration, two in the 1000 mOsm/L osmolarity limit and one in the 900 mOsm/L osmolarity limit cohort (p = 0.6). CONCLUSION: A lower PPN osmolarity limit of 900 mOsm/L significantly limited the ability to provide goal amino acid and IVFE doses to NICU patients compared to the previous osmolarity limit of 1000 mOsm/L without reducing the incidence of PIV infiltration or extravasation.

Chain-length dependent effects of inorganic polyphosphate on endothelial function and nucleotide pool.

Endothelial cells (ECs) are the first line that comes into contact with blood pathogens, pathogen-derived molecules, and factors that stimulate coagulation and inflammation. Inorganic polyphosphate (polyP) - a polymer of orthophosphate units synthesized by bacteria under stress and released by platelets upon their activation is among these factors. Bacterial and platelet polyPs differ in length, and both variants elicit different effects in eukaryotes. This study aimed to investigate how bacterial-like long-chain polyP (Lc-polyP) and platelet-like short-chain polyP (Sc-polyP) affect the functionality of cultured endothelial cells. Murine immortalized heart endothelial cells (H5V) were exposed to polyP of different chain lengths to assess the effects of these stimuli on intracellular energetics, permeability, and endothelial adhesion. We observed varying effects between Lc-polyP and Sc-polyP treatments. Lc-polyP more potently disturbs the intracellular ATP pool, a parameter strongly connected with vascular injury, whereas Sc-polyP robustly stimulates cellular adhesion to the endothelium. Both polymers similarly enhance endothelial permeability, suggesting potent immunomodulatory properties. This study provides evidence that polyP elicits profound cellular responses in endothelium depending on the polymer's length.

Fluid-Dynamic Culture of Tumour and Immune Cells for More Predictive Infiltration Studies and Immunotherapy Drug Screening.

Immunotherapies represent one of the current most promising challenges in cancer treatment. They are based on the boost of natural immune responses, aimed at cancer eradication. However, the success of immunotherapeutic approaches strictly depends on the interaction between immune cells and cancer cells. Preclinical drug tests currently available are poor in fully predicting the actual safety and efficacy of immunotherapeutic treatments under development. Indeed, conventional 2D cell culture underrepresents the complexity of the tumour microenvironment, while in vivo animal models lack in mimicking the human immune cell responses. In this context, predictability, reliability, and complete immune compatibility still represent challenges to overcome. For this aim, novel 3D, fully humanized in vitro cancer tissue models have been recently optimized by adopting emerging technologies, such as organ-on-chips (OOC) and 3D cancer cell-laden hydrogels. In particular, a novel multi-in vitro organ (MIVO) OOC platform has been recently adopted to culture 3D clinically relevant size cancer tissues under proper physiological culture conditions to investigate anti-cancer treatments and immune-tumour cell crosstalk.The proposed immune-tumour OOC-based model offers a potential tool for accurately modelling human immune-related diseases and effectively assessing immunotherapy efficacy, finally offering promising experimental approaches for personalized medicine.

A Versatile Microfluidic Platform for Extravasation Studies Based on DNA Origami-Cell Interactions.

The adhesion of circulating tumor cells (CTCs) to the endothelial lumen and their extravasation to surrounding tissues are crucial in the seeding of metastases and remain the most complex events of the metastatic cascade to study. Integrins expressed on CTCs are major regulators of the extravasation process. This knowledge is primarily derived from animal models and biomimetic systems based on artificial endothelial layers, but these methods have ethical or technical limitations. We present a versatile microfluidic device to study cancer cell extravasation that mimics the endothelial barrier by using a porous membrane functionalized with DNA origami nanostructures (DONs) that display nanoscale patterns of adhesion peptides to circulating cancer cells. The device simulates physiological flow conditions and allows direct visualization of cell transmigration through microchannel pores using 3D confocal imaging. Using this system, we studied integrin-specific adhesion in the absence of other adhesive events. Specifically, we show that the transmigration ability of the metastatic cancer cell line MDA-MB-231 is influenced by the type, distance, and density of adhesion peptides present on the DONs. Furthermore, studies with mixed ligand systems indicate that integrins binding to RGD (arginine-glycine-aspartic acid) and IDS (isoleucine-aspartic acid-serine) did not synergistically enhance the extravasation process of MDA-MB-231 cells.

CLINICAL PROTOCOLS ADOPTED BY NURSES IN THE EXTRAVASATION OF ANTINEOPLASTIC DRUGS: AN INTEGRATIVE REVIEW / PROTOCOLOS CLÍNICOS ADOPTADOS POR ENFERMERÍA EN LA EXTRAVASACIÓN DE FÁRMACOS ANTINEOPLÁSICOS: UNA REVISIÓN INTEGRADORA / PROTOCOLOS CLÍNICOS ADOTADOS PELOS ENFERMEIROS NO EXTRAVASAMENTO DE ANTINEOPLÁSICOS: UMA REVISÃO INTEGRATIVA

Objective: To identify the patient safety measures and clinical protocols adopted by nurses in the case of antineoplastic extravasation. Methodology: The research approach was based on an integrative literature review that used the PICo strategy to structure the research question. Bibliographic surveys were carried out using the MEDLINE, Lilacs, BDENF, SciELO and PubMed databases using the following terms according to DeCS: "Clinical Protocols", " Extravasation of Therapeutic and Diagnostic Materials", "Oncology Nursing", "Patient Safety", "Antineoplastics". After applying the inclusion and exclusion criteria, 25 articles were selected, read in full, classified and organized according to the theme, and critically analyzed. Results: From the analysis of the studies, it was possible to delimit the main actions and knowledge of nurses in the management and guarantee of patient safety in the face of antineoplastic extravasation, as well as promising new managements in the prevention and treatment of this aggravation. Conclusion: Nurses' knowledge of specific measures for antineoplastic drug leakage is incipient, and there is a clear need for research to minimize the gaps in innovative knowledge in nursing practice with the aim of preventing extravasation.

Objetivo: Identificar las medidas de seguridad del paciente y los protocolos clínicos adoptados por el personal de enfermería en el caso de extravasación de antineoplásicos. Metodología: El abordaje de la investigación se basó en una revisión bibliográfica integradora que utilizó la estrategia PICo para estructurar la pregunta de investigación. Las pesquisas bibliográficas fueron realizadas en las bases de datos MEDLINE, Lilacs, BDENF, SciELO y PubMed, utilizando los siguientes términos de acuerdo con el DeCS: "Protocolos clínicos", " Extravasación de material terapéutico y de diagnóstico", "Enfermería oncológica", "Seguridad del paciente", "Antineoplásicos". Tras aplicar los criterios de inclusión y exclusión, se seleccionaron 25 artículos, que fueron leídos en su totalidad, clasificados y organizados según el tema, y analizados críticamente. Resultados: A partir del análisis de los estudios, fue posible delinear las principales acciones y conocimientos de las enfermeras en el manejo y garantía de la seguridad del paciente ante la extravasación de antineoplásicos, así como nuevos manejos promisorios en la prevención y tratamiento de este agravamiento. Conclusión: El conocimiento de las enfermeras sobre las medidas específicas para la fuga de fármacos antineoplásicos es incipiente, existiendo una clara necesidad de investigación para minimizar las lagunas de conocimiento innovador en la práctica enfermera con el objetivo de prevenir la extravasación.

Objetivo: Identificar quais são as medidas de segurança do paciente e protocolos clínicos adotados pelos enfermeiros no extravasamento de antineoplásicos. Metodologia: A abordagem da pesquisa se deu a partir de uma revisão integrativa da literatura que se utilizou da estratégia PICo para estruturar a questão de pesquisa. Foram realizados levantamentos bibliográficos utilizando as bases de dados MEDLINE, Lilacs, BDENF, SciELO e PubMed utilizando os termos segundo o DeCS: "Protocolos Clínicos", "Extravasamento de Materiais Terapêuticos e Diagnósticos", "Enfermagem Oncológica", "Segurança do paciente", "Antineoplásicos". Após a aplicação dos critérios de inclusão e exclusão, foram selecionados 25 artigos lidos na íntegra, classificados e organizados conforme a temática, e analisados criticamente. Resultados: A partir da análise dos estudos, foi possível delimitar as principais ações e conhecimentos dos enfermeiros no manejo e garantia da segurança do paciente diante do extravasamento de antineoplásicos, assim como novos manejos promissores na prevenção e tratamento deste agravo. Conclusão: Incipiente é o conhecimento dos enfermeiros sobre as medidas específicas diante do extravasamento de antineoplásicos, com evidente necessidade de pesquisas que minimizem as lacunas no conhecimento inovador na prática da enfermagem com desígnio de prevenir  o extravasamento.

Extravasation and infiltration: under-recognised complications of intravenous therapy.

Occasionally, the administration of intravenous (IV) therapies can go wrong. Infiltration or extravasation is a complication when a drug or IV therapy leaks into the tissues surrounding the vascular access device. Extravasation can cause serious and often life-changing injuries. Extravasation is often associated with systemic anti-cancer therapy but non-chemotherapy drugs have been reported as having a greater risk of serious complications. This study outlines the first UK Infusion unit evaluation of the ivWatch infusion monitoring device which was undertaken from August 2023 to January 2024. Out of 2254 infusions monitored with ivWatch, the device prevented 122 cases of infiltration and extravasation from causing any harm to the patient, corresponding to a 5.4% 'check IV' notification rate.

The multiple strategies adopted in a complex case of calcium extravasation in a child: a case report.

Extravasation of calcium solution is a common adverse event in children in intensive care units. The lack of adequate and timely treatment can lead to important functional sequelae. Here, we report the case of calcium extravasation in a child and we discuss the multiple therapeutic strategies adopted.