Tissue resident iNKT17 cells facilitate cancer cell extravasation in liver metastasis via interleukin-22.

During metastasis, cancer cells invade, intravasate, enter the circulation, extravasate, and colonize target organs. Here, we examined the role of interleukin (IL)-22 in metastasis. Immune cell-derived IL-22 acts on epithelial tissues, promoting regeneration and healing upon tissue damage, but it is also associated with malignancy. Il22-deficient mice and mice treated with an IL-22 antibody were protected from colon-cancer-derived liver and lung metastasis formation, while overexpression of IL-22 promoted metastasis. Mechanistically, IL-22 acted on endothelial cells, promoting endothelial permeability and cancer cell transmigration via induction of endothelial aminopeptidase N. Multi-parameter flow cytometry and single-cell sequencing of immune cells isolated during cancer cell extravasation into the liver revealed iNKT17 cells as source of IL-22. iNKT-cell-deficient mice exhibited reduced metastases, which was reversed by injection of wild type, but not Il22-deficient, invariant natural killer T (iNKT) cells. IL-22-producing iNKT cells promoting metastasis were tissue resident, as demonstrated by parabiosis. Thus, IL-22 may present a therapeutic target for prevention of metastasis.

Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation.

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation.

Age-related changes in the local milieu of inflamed tissues cause aberrant neutrophil trafficking and subsequent remote organ damage.

Aging is associated with dysregulated immune functions. Here, we investigated the impact of age on neutrophil diapedesis. Using confocal intravital microscopy, we found that in aged mice, neutrophils adhered to vascular endothelium in inflamed tissues but exhibited a high frequency of reverse transendothelial migration (rTEM). This retrograde breaching of the endothelium by neutrophils was governed by enhanced production of the chemokine CXCL1 from mast cells that localized at endothelial cell (EC) junctions. Increased EC expression of the atypical chemokine receptor 1 (ACKR1) supported this pro-inflammatory milieu in aged venules. Accumulation of CXCL1 caused desensitization of the chemokine receptor CXCR2 on neutrophils and loss of neutrophil directional motility within EC junctions. Fluorescent tracking revealed that in aged mice, neutrophils undergoing rTEM re-entered the circulation and disseminated to the lungs where they caused vascular leakage. Thus, neutrophils stemming from a local inflammatory site contribute to remote organ damage, with implication to the dysregulated systemic inflammation associated with aging.

Directional mast cell degranulation of tumor necrosis factor into blood vessels primes neutrophil extravasation.

Tissue resident mast cells (MCs) rapidly initiate neutrophil infiltration upon inflammatory insult, yet the molecular mechanism is still unknown. Here, we demonstrated that MC-derived tumor necrosis factor (TNF) was crucial for neutrophil extravasation to sites of contact hypersensitivity-induced skin inflammation by promoting intraluminal crawling. MC-derived TNF directly primed circulating neutrophils via TNF receptor-1 (TNFR1) while being dispensable for endothelial cell activation. The MC-derived TNF was infused into the bloodstream by directional degranulation of perivascular MCs that were part of the vascular unit with access to the vessel lumen. Consistently, intravenous administration of MC granules boosted neutrophil extravasation. Pronounced and rapid intravascular MC degranulation was also observed upon IgE crosslinking or LPs challenge indicating a universal MC potential. Consequently, the directional MC degranulation of pro-inflammatory mediators into the bloodstream may represent an important target for therapeutic approaches aimed at dampening cytokine storm syndromes or shock symptoms, or intentionally pushing immune defense.

Distinct Compartmentalization of the Chemokines CXCL1 and CXCL2 and the Atypical Receptor ACKR1 Determine Discrete Stages of Neutrophil Diapedesis.

Neutrophils require directional cues to navigate through the complex structure of venular walls and into inflamed tissues. Here we applied confocal intravital microscopy to analyze neutrophil emigration in cytokine-stimulated mouse cremaster muscles. We identified differential and non-redundant roles for the chemokines CXCL1 and CXCL2, governed by their distinct cellular sources. CXCL1 was produced mainly by TNF-stimulated endothelial cells (ECs) and pericytes and supported luminal and sub-EC neutrophil crawling. Conversely, neutrophils were the main producers of CXCL2, and this chemokine was critical for correct breaching of endothelial junctions. This pro-migratory activity of CXCL2 depended on the atypical chemokine receptor 1 (ACKR1), which is enriched within endothelial junctions. Transmigrating neutrophils promoted a self-guided migration response through EC junctions, creating a junctional chemokine "depot" in the form of ACKR1-presented CXCL2 that enabled efficient unidirectional luminal-to-abluminal migration. Thus, CXCL1 and CXCL2 act in a sequential manner to guide neutrophils through venular walls as governed by their distinct cellular sources.

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.

PECAM-1 supports leukocyte diapedesis by tension-dependent dephosphorylation of VE-cadherin.

Leukocyte extravasation is an essential step during the immune response and requires the destabilization of endothelial junctions. We have shown previously that this process depends in vivo on the dephosphorylation of VE-cadherin-Y731. Here, we reveal the underlying mechanism. Leukocyte-induced stimulation of PECAM-1 triggers dissociation of the phosphatase SHP2 which then directly targets VE-cadherin-Y731. The binding site of PECAM-1 for SHP2 is needed for VE-cadherin dephosphorylation and subsequent endocytosis. Importantly, the contribution of PECAM-1 to leukocyte diapedesis in vitro and in vivo was strictly dependent on the presence of Y731 of VE-cadherin. In addition to SHP2, dephosphorylation of Y731 required Ca2+ -signaling, non-muscle myosin II activation, and endothelial cell tension. Since we found that ß-catenin/plakoglobin mask VE-cadherin-Y731 and leukocyte docking to endothelial cells exert force on the VE-cadherin-catenin complex, we propose that leukocytes destabilize junctions by PECAM-1-SHP2-triggered dephosphorylation of VE-cadherin-Y731 which becomes accessible by actomyosin-mediated mechanical force exerted on the VE-cadherin-catenin complex.

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.

Cholesterol synthesis is essential for the growth of liver metastasis-prone colorectal cancer cells.

Metastasis to the liver is a leading cause of death in patients with colorectal cancer. To investigate the characteristics of cancer cells prone to metastasis, we utilized an isogenic model of BALB/c and colon tumor 26 (C26) cells carrying an active KRAS mutation. Liver metastatic (LM) 1 cells were isolated from mice following intrasplenic transplantation of C26 cells. Subsequent injections of LM1 cells generated LM2 cells, and after four cycles, LM4 cells were obtained. In vitro, using a perfusable capillary network system, we found comparable extravasation frequencies between C26 and LM4 cells. Both cell lines showed similar growth rates in vitro. However, C26 cells showed higher glucose consumption, whereas LM4 cells incorporated more fluorescent fatty acids (FAs). Biochemical analysis revealed that LM4 cells had higher cholesterol levels than C26 cells. A correlation was observed between fluorescent FAs and cholesterol levels detected using filipin III. LM4 cells utilized FAs as a source for cholesterol synthesis through acetyl-CoA metabolism. In cellular analysis, cholesterol accumulated in punctate regions, and upregulation of NLRP3 and STING proteins, but not mTOR, was observed in LM4 cells. Treatment with a cholesterol synthesis inhibitor (statin) induced LM4 cell death in vitro and suppressed LM4 cell growth in the livers of nude mice. These findings indicate that colorectal cancer cells prone to liver metastasis show cholesterol-dependent growth and that statin therapy could help treat liver metastasis in immunocompromised patients.

Real-time visualization of dextran extravasation in intermittent hypoxia mice using noninvasive SWIR imaging.

Imaging tools are crucial for studying the vascular network and its barrier function in various physiopathological conditions. Shortwave infrared (SWIR) window optical imaging allows noninvasive, in-depth exploration. We applied SWIR imaging, combined with vessel segmentation and deep learning analyses, to study real-time dextran probe extravasation in mice experiencing intermittent hypoxia (IH)-a characteristic of obstructive sleep apnea associated with potential cardiovascular alterations due to early vascular permeability. Evidence for permeability in this context is limited, making our investigation significant. C57Bl/6 mice were exposed to normoxia or intermittent hypoxia for 14 days. Then SWIR imaging between 1,250 and 1,700 nm was performed on the saphenous artery and vein and on the surrounding tissue after intravenous injection of labeled dextrans of two different sizes (10 or 70 kDa). Postprocessing and segmentation of the SWIR images were conducted using deep learning treatment. We monitored high-resolution signals, distinguishing arteries, veins, and surrounding tissues. In the saphenous artery and vein, after 70-kD dextran injection, tissue/vessel ratio was higher after intermittent hypoxia (IH) than normoxia (N) over 500 seconds (P < 0.05). However, the ratio was similar in N and IH after 10-kD dextran injection. The SWIR imaging technique allows noninvasive, real-time monitoring of dextran extravasation in vivo. Dextran 70 extravasation is increased after exposure to IH, suggesting an increased vessel permeability in this mice model of obstructive sleep apnea.NEW & NOTEWORTHY We demonstrate that SWIR imaging technique is a useful tool to monitor real-time dextran extravasation from vessels in vivo, with a high resolution. We report for the first time an increased real-time dextran (70 kD) extravasation in mice exposed to intermittent hypoxia for 14 days compared with normoxic controls.

Soluble vascular endothelial glycocalyx proteoglycans as potential therapeutic targets in inflammatory diseases.

Reducing the activity of cytokines and leukocyte extravasation is an emerging therapeutic strategy to limit tissue-damaging inflammatory responses and restore immune homeostasis in inflammatory diseases. Proteoglycans embedded in the vascular endothelial glycocalyx, which regulate the activity of cytokines to restrict the inflammatory response in physiological conditions, are proteolytically cleaved in inflammatory diseases. Here we critically review the potential of proteolytically shed, soluble vascular endothelial glycocalyx proteoglycans to modulate pathological inflammatory responses. Soluble forms of the proteoglycans syndecan-1, syndecan-3 and biglycan exert beneficial anti-inflammatory effects by the removal of chemokines, suppression of proinflammatory cytokine expression and leukocyte migration, and induction of autophagy of proinflammatory M1 macrophages. By contrast, soluble versikine and decorin enhance proinflammatory responses by increasing inflammatory cytokine synthesis and leukocyte migration. Endogenous syndecan-2 and mimecan exert proinflammatory effects, syndecan-4 and perlecan mediate beneficial anti-inflammatory effects and glypican regulates Hh and Wnt signaling pathways involved in systemic inflammatory responses. Taken together, targeting the vascular endothelial glycocalyx-derived, soluble syndecan-1, syndecan-2, syndecan-3, syndecan-4, biglycan, versikine, mimecan, perlecan, glypican and decorin might be a potential therapeutic strategy to suppress overstimulated cytokine and leukocyte responses in inflammatory diseases.

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.

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.

Beyond the barrier: the immune-inspired pathways of tumor extravasation.

Extravasation is a fundamental step in the metastatic journey, where cancer cells exit the bloodstream and breach the endothelial cell barrier to infiltrate target tissues. The tactics cancer cells employ are sophisticated, closely reflecting those used by the immune system for tissue surveillance. Remarkably, tumor cells have been observed to form distinct associations or clusters with immune cells where neutrophils stand out as particularly crucial partners. These interactions are not accidental; they are critical for cancer cells to exploit the immune functions of neutrophils and successfully extravasate. In another strategy, tumor cells mimic the behavior and characteristics of immune cells. They release a suite of inflammatory mediators, which under normal circumstances, guide the processes of endothelium reshaping and facilitate the entry and movement of immune cells within tissues. In this review, we offer a new perspective on the tactics employed by cancer cells to extravasate and infiltrate target tissues. We delve into the myriad mechanisms that tumor cells borrow, adapt, and refine from the immune playbook. Video Abstract.

Checking vesicourethral anastomosis for urinary extravasation during radical prostatectomy: is it still necessary in the robotic era? A prospective, randomized case-control study.

PURPOSE: This study aims to evaluate the role of intraoperative control of the watertightness of vesicourethral anastomosis extravasation control (VUAEC) in predicting vesicourethral anastomosis (VUA) healing and early postoperative outcomes in patients undergoing robot-assisted radical prostatectomy (RARP). METHODS: 100 patients who underwent RARP between October 2020 and May 2023 were consecutively included in the study. Preoperatively, the patients were randomized to undergo VUAEC (Group-A) or not (Group-B). Patients in Group-A were evaluated in 2 subgroups: those with no extravasation observed during VUAEC (Group-A1; n = 31 (62%)) and those with extravasation (Group-A2; n = 19 (38%)). On the 8th post-operative day, a gravity cystogram (GC) was performed on all patients to assess VUA healing. RESULTS: There was no statistically significant difference between the groups in terms of clinical features, drain removal time, length of hospital stay, extravasation on GC, catheter removal time and postoperative complications (p > 0.05, for each). There was also no statistically significant difference between the subgroups in terms of drain removal time, length of hospital stays, catheter removal time (p > 0.05, for each). In Group-A2, urinary extravasation on GC was found in a greater percentage, but the difference remained statistically insignificant (p = 0.082). CONCLUSIONS: Performing intraoperative VUAEC did not have a significant role in the prediction of VUA healing and early postoperative outcomes in patients undergoing RARP. The current study did not identify a substantial clinical benefit of routine intraoperative VUAEC.

CT Texture-Based Nomogram in Ischemic Stroke to Differentiate Intracerebral Hemorrhage from Contrast Extravasation after Thrombectomy.

INTRODUCTION: Post-thrombectomy intraparenchymal hyperdensity (PTIH) in patients with acute ischemic stroke is a common CT sign, making it difficult for physicians to distinguish intracerebral hemorrhage in the early post-thrombectomy period. The aim of this study was to develop an effective model to differentiate intracerebral hemorrhage from contrast extravasation in patients with PTIH. METHODS: We retrospectively collected information on patients who underwent endovascular thrombectomy at two stroke centers between August 2017 and January 2023. A total of 222 patients were included in the study, including 118 patients in the development cohort, 52 patients in the internal validation cohort, and 52 patients in the external validation cohort. The nomogram was constructed using R software based on independent predictors derived from the multivariate logistic regression analysis, including clinical factors and CT texture features extracted from hyperdense areas on CT images. The performance and accuracy of the derived nomogram were assessed by the area under the receiver operating characteristic curve (AUC-ROC) and calibration curves. Additionally, decision curve analysis was conducted to appraise the clinical utility of the nomogram. RESULTS: Our nomogram was derived from two clinical factors (ASPECT score and onset to reperfusion time) and two CT texture features (variance and uniformity), with AUC-ROC of 0.943, 0.930, and 0.937 in the development, internal validation, and external validation cohorts, respectively. Furthermore, the calibration plot exhibited a strong agreement between the predicted outcome and the actual outcome. In addition, the decision curve analysis revealed the clinical utility of the nomogram in accurately predicting hemorrhage in patients with PTIH. CONCLUSION: The developed nomogram, based on clinical factors and CT texture features, proves to be effective in distinguishing intracerebral hemorrhage from contrast extravasation in patients with PTIH.

Safety of Peripherally Infused Sympathomimetic Vasopressors in the Intensive Care Unit and Emergency Department.

BACKGROUND: Sympathomimetic vasopressors may be administered through a peripheral catheter, but there are limited data available on the safety of peripheral use. OBJECTIVE: The purpose of this study was to analyze the safety of peripherally infused sympathomimetic vasopressors. METHODS: A multicenter, retrospective observational study was conducted to evaluate patients who received peripheral vasopressors. The study's primary outcome was to assess the incidence of extravasation during the administration of peripheral vasopressors. Secondary outcomes include avoidance of central venous catheter (CVC) placement and institution protocol deviations. RESULTS: There were 198 patients included in the study, of which 142 patients received norepinephrine, 48 patients received phenylephrine, and 8 patients received epinephrine peripherally. Extravasation events occurred in 11 (5.6%) patients. Seven patients required a pharmacologic antidote and 10 patients required a warm compress. No significant differences were seen in characteristics of patients who extravasated compared with those who did not. Protocol deviations identified during the study included 24 (12.1%) patients receiving doses above the protocol maximum, 19 (9.6%) with a body mass index above the protocol maximum, and 45 (22.7%) patients receiving peripheral vasopressor over 24 hours. The majority of patients were able to avoid CVC placement (59.1%). CONCLUSION AND RELEVANCE: Peripherally infused sympathomimetic vasopressors are safe to administer up to 24 hours with a low incidence of extravasation events while avoiding CVC placement in the majority of patients.

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.

GEDEFO-SEFH management of antineoplastic extravasations survey results.

INTRODUCTION: Extravasation is a potentially severe complication of intravenous administration of antineoplastic drugs. The limited data makes it difficult to develop an optimal management scheme. The objective of this study is to describe the clinical practice in the extravasation management of antineoplastic agents in Spanish centers. METHODS: An online survey was distributed to oncology pharmacists using the email distribution list of the Spanish Society of Hospital Pharmacists. Respondents were surveyed on the standard operational protocol (SOP) of extravasation, tissue damage risk classification, and specific measures of extravasation management. RESULTS: A total of 68 surveys were completed. A specific extravasation SOP was available in 82.4% centers. The pharmacist participates in the authorship (100%) and actively collaborates in extravasation management (76.5%). A tissue damage risk classification based on the three categories was mostly adopted (48.2%) and 73.2% applied specific criteria based on concentration and/or extravasated volume. Extravasation management was mainly performed with the application of physical measures and/or antidotes (91.2%). High variability in the choices of pharmacological and/or physical measures recommended is outstanding. CONCLUSION: The results of this study highlight the involvement of Spanish pharmacists in extravasation management, the application of physical measures and/or pharmacological measures as the method of choice in extravasation management, as well as the existing discrepancies in tissue damage risk classification and management recommendations.

Feasibility of preventing massive contrast media extravasation using a sensor device in contrast-enhanced CT: an observational study.

BACKGROUND: Recent guidelines recommend direct patient observation, pressure monitoring, and sensor devices to prevent extravasation during contrast media (CM) injection. However, it is impractical in terms of time and cost to install sensors for all patients. PURPOSE: To identify risk factors for CM extravasations during contrast-enhanced computed tomography (CECT) in a large population and to establish criteria for placing the sensor device on patients. MATERIAL AND METHODS: This retrospective study included 143,556 patients who underwent CECT at our hospital between April 2012 and July 2022. We performed multivariable logistic regression analysis between patients with (n = 350) and randomly selected patients without CM extravasation (n = 350). We investigated the percentage of patients with sensor devices and their sensitivity for detecting extravasation using receiver operating characteristic curve analysis. RESULTS: The extravasation rate was 0.27%. Multivariable logistic regression analysis showed that the injection rate (adjusted odds ratio [AOR] = 1.61, 95% confidence interval [CI] = 1.33-1.95: P <0.001), catheter gauge (AOR = 3.86, 95% CI = 1.92-7.76; P <0.001), the use of anticancer drugs (AOR = 1.81, 95% CI = 1.32-2.50; P <0.001), and existing catheters (AOR = 1.52, 95% CI = 1.10-2.11; P = 0.009) were significantly associated with extravasation. To achieve a sensitivity of 90%, 80%, 70%, 60%, and 50%, 80%, 65%, 50%, 40%, and 28% of all patients required the placement of a sensor device, respectively. CONCLUSION: Sensitivity analysis established criteria for effective placing sensor devices.