Oxaliplatin-Induced Peripheral Neuropathy Can Be Minimized By Pressurized Regional Intravascular Delivery In An Orthotopic Murine Pancreatic Cancer Model.

Purpose: There is a great need to reduce the toxicity of chemotherapy used in the management of pancreatic ductal adenocarcinoma (PDAC). Here we explore if regional pressurized delivery of oxaliplatin can minimize peripheral neuropathy in mice.Methods: We used an orthotopic PDAC mouse model and delivered a single dose of oxaliplatin through the portal vein using a pressure-enabled system (pancreatic retrograde venous infusion, PRVI). We analyzed the effects of PRVI on tumor burden and peripheral neuropathy using histopathological and functional assays.Results: Tumor weights in mice treated with 2 mg/Kg oxaliplatin using PRVI were significantly lower than in mice treated with the same dose systemically. This resulted in reduced peripheral neuropathy signatures in PRVI mice compared to the 20 mg/Kg systemic dose required to achieve similar tumor control.Conclusion: Regional delivery of highly cytotoxic agents using PRVI can reduce the therapeutic dose of these drugs, thereby lowering toxic side effects.

Health Informatics Study of Related Complications Relating to Upper Arm Implantable Intravenous Infusion Port in Breast Cancer Patients

Objective: In order to explore the clinical application effect of the upper arm venous infusion port, analyze the prevention and treatment effect of catheter rupture of the upper arm venous infusion port, and conduct a series of studies on postoperative related complications, as well as analyze the prevention and treatment of catheter rupture of the upper arm venous infusion port effect using chest radiography and computed tomography. Methods: We collected clinical data of 98 patients implanted in the upper arm venous infusion port in the Second Affiliated Hospital of Zhejiang University of Traditional Chinese Medicine and Hangzhou Shulan Hospital from January to December 2017, divided the 98 patients into two groups, and gave 49 patients in group A Based on the patient’s basic intervention, 49 patients in group B were given prevention and treatment intervention of catheter rupture, and the intervention effects of the two groups were compared. Consult the nursing records during the hospitalization and maintenance period after the implantation of the upper arm vein infusion port, summarize the complications, analyze the causes, and discuss the formulation of feasible nursing countermea-sures. Results: 98 patients were followed up for 5-16 months, with a median follow-up time of 10 months. Within 2 weeks after implantation of the upper arm vein infusion port and during discharge maintenance, the incidence of complications was 24.49% (24/98), 8.16% (8/98), the difference in the incidence of complications between the two time periods was statistically significant (P < 0.05). Among them, common complications include incision bleeding at the port body, poor healing of the incision, local swelling, obstruction of catheter withdrawal, extravasation of transfusion at the port body, catheter blockage, catheter displacement, and catheter-related thrombosis. There was a difference in the incidence of catheter rupture, catheter rupture time, and patient satisfaction after intervention between the two groups of intravenous implantation patients (P < 0.05), which was statistically significant. Conclusions: Complications within 2 weeks after implantation of the upper arm venous infusion port are significantly higher than the maintenance period. Among them, infusion extravasation, catheter-related thrombosis, catheter blockage, and catheter displacement at the port body are serious complications that directly affect the use of the upper arm infusion port . The prevention and treatment of catheter rupture for patients who have used implanted intravenous infusion ports for a long time has significant effects, which can reduce the occurrence of catheter rupture and ensure the safety of patients’ lives and health.

Pressure-Enabled Drug Delivery Approach in the Pancreas with Retrograde Venous Infusion of Lipiodol with Ex Vivo Analysis

Purpose To determine the safety and feasibility of pancreatic retrograde venous infusion (PRVI) utilizing a microvalvular infusion system (MVI) to deliver ethiodized oil (lipiodol) by means of the Pressure-Enabled Drug Delivery (PEDD) approach. Methods Utilizing transhepatic access, mapping of the pancreatic body and head venous anatomy was performed in 10 swine. PEDD was performed by cannulation of veins in the head (n = 4) and body (n = 10) of the pancreas with a MVI (Surefire® Infusion System (SIS), Surefire Medical, Inc (DBA TriSalus™ Life Sciences)) followed by infusion with lipiodol. Sets of animals were killed either immediately (n = 8) or at 4 days post-PRVI (n = 2). All pancreata were harvested and studied with micro-CT and histology. We also performed three-dimensional volumetric/multiplanar imaging to assess the vascular distribution of lipiodol within the glands. Results A total of 14 pancreatic veins were successfully infused with an average of 1.7 (0.5–2.0) mL of lipiodol. No notable change in serum chemistries was seen at 4 days. The signal-to-noise ratio (SNR) of lipiodol deposition was statistically increased both within the organ in target relative to non-target pancreatic tissue and compared to extra pancreatic tissue (p < 0.05). Histological evaluation demonstrated no evidence of pancreatic edema or ischemia. Conclusions PEDD using the RVI approach for targeted pancreatic infusions is technically feasible and did not result in organ damage in this pilot animal study.

Concomitant placement of dialysis and infusion catheters in the right internal jugular vein in the intensive care setting: Is it safe?

Purpose: This study examined the safety and efficacy of placing both a central venous dialysis catheter and a central venous catheter for infusion in the right internal jugular vein compared to only a central venous dialysis catheter. Methods: We conducted a retrospective chart review for all adult patients who underwent the placement of the right internal jugular dialysis catheter by a single surgeon. Patients were grouped based on whether they received a tunneled dual lumen dialysis catheter alone or in combination with a central venous infusion catheter in the right internal jugular vein. Catheter-related thrombosis, line infections, line malfunctions, pneumothorax, and need for line replacement were evaluated. Results: There were 97 patients in the dialysis catheter and central venous infusion line group and 63 patients in the dialysis catheter only group. The two groups were not different with regard to age (62.1 ± 16.3 years vs 57.9 ± 17.6 years) and gender (47.4% male vs 55.6% male). No significant differences were found in the incidence of thrombosis (1.0 % vs 0.0%, p > 0.999), line infection (2.1% vs 0.0%, p = 0.519), or line malfunctions (2.1% vs 0.0%, p = 0.516) in patients who did or did not have a central venous infusion catheter placed concomitantly with the dialysis catheter, respectively. No patients in either group had a pneumothorax. Conclusions: Although not currently utilized with frequency, these preliminary data indicate that placing both a dual lumen dialysis catheter and central venous infusion catheter in the right internal jugular simultaneously could be a viable option.

Comparison of gemcitabine delivery and tumor response in a pressurized pancreatic retrograde venous infusion versus systemic infusion in an orthotopic murine model.

737 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with limited response to systemic therapy (ST). Elevated tumor interstitial fluid pressures (IFP) inhibit penetration of ST. Regional Pressure Enabled Drug Delivery has recently demonstrated improved response for liver tumors in a clinical trial. However, this delivery method has not been evaluated in PDAC. We compared gemcitabine (Gem) by systemic delivery vs. a novel pressurized Pancreatic Retrograde Venous Infusion (PRVI) method in an orthotopic PDAC mouse model. Methods: PDAC murine cell line (KPC4580P) tumors were transplanted onto the pancreatic tail of C57BL/6J mice. Groups of 15 mice were randomly assigned to PRVI Gem, PRVI saline (Control), or intraperitoneal Gem (Systemic) groups. Five mice from the PRVI and Systemic groups were randomly selected after one hour post infusion to evaluate Gem tumor concentrations by liquid chromatography - tandem mass spectrometry (ng/mg), and the remainder of mice were euthanized after 7 days to evaluate treatment response. Results: Tumor concentrations of Gem were significantly higher following PRVI compared to Systemic (128 vs. 19, p < 0.01) at one hour after treatment. Seven days after treatment, PRVI Gem mice demonstrated lower mean tumor volume (mm3) than Systemic Gem and Control mice (274 vs. 857 vs. 629, p < 0.01), respectively. Histologic evaluation of tumors demonstrated decreased cellularity in the PRVI Gem mice compared to Systemic and Control mice (35 vs. 78 vs. 71%, p = 0.01), respectively. No differences were seen in Ki67% or immune cell infiltrate between groups. Conclusions: PRVI delivery resulted in increased PDAC Gem concentrations and improved treatment responses with decreased tumor burden and cellularity. These findings suggest that pressurized regional chemotherapy infusion overcomes the elevated PDAC IFP and justifies additional translational pre-clinical studies with other chemotherapeutics (including immunomodulating antibodies) with different physicochemical properties.

Acid-sensing ion channels blockade attenuates pressor and sympathetic responses to skeletal muscle metaboreflex activation in humans

In animals, the blockade of acid-sensing ion channels (ASICs), cation pore-forming membrane proteins located in the free nerve endings of group IV afferent fibers, attenuates increases in arterial pressure (AP) and sympathetic nerve activity (SNA) during muscle contraction. Therefore, ASICs play a role in mediating the metabolic component (skeletal muscle metaboreflex) of the exercise pressor reflex in animal models. Here we tested the hypothesis that ASICs also play a role in evoking the skeletal muscle metaboreflex in humans, quantifying beat-by-beat mean AP (MAP; finger photoplethysmography) and muscle SNA (MSNA; microneurography) in 11 men at rest and during static handgrip exercise (SHG; 35% of the maximal voluntary contraction) and postexercise muscle ischemia (PEMI) before (B) and after (A) local venous infusion of either saline or amiloride (AM), an ASIC antagonist, via the Bier block technique. MAP (BAM +30 ± 6 vs. AAM +25 ± 7 mmHg, P = 0.001) and MSNA (BAM +14 ± 9 vs. AAM +10 ± 6 bursts/min, P = 0.004) responses to SHG were attenuated under ASIC blockade. Amiloride also attenuated the PEMI-induced increases in MAP (BAM +25 ± 6 vs. AAM +16 ± 6 mmHg, P = 0.0001) and MSNA (BAM +16 ± 9 vs. AAM +8 ± 8 bursts/min, P = 0.0001). MAP and MSNA responses to SHG and PEMI were similar before and after saline infusion. We conclude that ASICs play a role in evoking pressor and sympathetic responses to SHG and the isolated activation of the skeletal muscle metaboreflex in humans. NEW & NOTEWORTHY We showed that regional blockade of the acid-sensing ion channels (ASICs), induced by venous infusion of the antagonist amiloride via the Bier block anesthetic technique, attenuated increases in arterial pressure and muscle sympathetic nerve activity during both static handgrip exercise and postexercise muscle ischemia. These findings indicate that ASICs contribute to both pressor and sympathetic responses to the activation of the skeletal muscle metaboreflex in humans.

Lower retention after retrograde coronary venous infusion compared with intracoronary infusion of mesenchymal stromal cells in the infarcted porcine myocardium

BackgroundCommonly used strategies for cell delivery to the heart are intramyocardial injection and intracoronary (IC) infusion, both having their advantages and disadvantages. Therefore, alternative strategies, such as retrograde coronary venous infusion (RCVI), are explored. The aim of this confirmatory study was to compare cardiac cell retention between RCVI and IC infusion. As a secondary end point, the procedural safety of RCVI is assessed.MethodsFour weeks after myocardial infarction, 12 pigs were randomised to receive mesenchymal stromal cells, labelled with Indium-111, via RCVI (n=6) or IC infusion (n=6). Four hours after cell administration, nuclear imaging was performed to determine the number of cells retained in the heart both in vivo and ex vivo. Procedure-related safety measures were reported.ResultsCardiac cell retention is significantly lower after RCVI compared with IC infusion (in vivo: RCVI: median 2.89% vs IC: median 13.74%, p=0.002, ex vivo: RCVI: median 2.55% vs IC: median 39.40%, p=0.002). RCVI led to development of pericardial fluid and haematomas on the frontal wall of the heart in three cases. Coronary venous dissection after RCVI was seen in three pigs, of which one also developed pericardial fluid and a haematoma. IC infusion led to no flow in one pig.ConclusionRCVI is significantly less efficient in delivering cells to the heart compared with IC infusion. RCVI led to more procedure-related safety issues than IC infusion, with multiple cases of venous dissection and development of haematomas and pericardial fluid collections.