Infusion Of Solution Research Articles

A-192 Cause and Departmental Origin of Errors—An Investigation of Questionable Patient Test Results

Abstract Introduction Reliable patient test results are crucial for quality patient care, involving pre-, post- and analytical phases. Questionable Patient test Results (QPRs), either not matching patient clinical presentation or apparent outliers for the patient population, are often encountered. We aimed to investigate the source and nature of possible errors that cause QPRs. Methods 960 QPRs were identified during July-December 2022 at our institution. We examined the nature of the QPRs, the corresponding patient clinical records, the procedures involved in pre-, post- and analytical phases, and quality control systems. Results The QPRs were found to be originated from 31 departments and medical specialty units. Of those, 5 departments/units had >50 QPRs (accounting for 64% of total QPRs) and are listed in the table provided. The table also lists the information on 7 types of errors identified by our analysis. Of all errors, 78% occurred at pre-analytical phase, with the majority of errors occurring during sample collection. Discussion The most common types of errors were either diluted or contaminated samples accounting for 38% and 34%, respectively. Such errors often occur during sample drawing from an existing I.V. access port if not adequately flushed after saline solution infusion (causing sample dilution) or dextrose solution (causing glucose contamination). Many errors were due to samples drawn in the wrong collection tube type. Sample integrity issues included hemolysis, lack of sufficient sample volume, or clotting. For those QPRs that we did not find apparent errors, they were either due to random errors or the results fit the patient’s true medical condition. Conclusions Our findings highlight the importance of pre-analytical quality control measures and the need for regular staff education/training. This study pinpointed the errors that require targeted education materials, as well as the hospital units that would benefit most from this focus on error prevention.

Tuning Molecular Orientation Responses of Microfluidic Liquid Crystal Dispersions to Colloid and Polymer Flows.

An important approach to molecular diagnostics is integrating organized substances that provide complex molecular level responses to introduced chemical and biological agents with conditions that optimize and distinguish such responses. In this respect, liquid crystal dispersions are attractive components of molecular diagnostic tools. This paper analyzes a colloid system, containing a nematic liquid crystal as a dispersed phase, and aqueous surfactant and polymer solutions as the continuous phases. We applied a microfluidic approach for tuning orientation of liquid crystal molecules in picoliter droplets immobilized on microchannel walls. Introduction of surfactant to the aqueous phase was found to proportionally increase the order parameter of liquid crystal molecules in microdroplets. Infusion of polymer solutions into surfactant-mediated microfluidic liquid crystal dispersions increased the order parameter at much lower surfactant concentrations, while further infusion of surfactant solutions randomized the orientation of liquid crystal molecules. These effects were correlated with the adsorption of surfactant molecules on surfaces of microdroplets, stabilizing the effect of a polymer matrix on bound surfactant ions and the formation of insoluble polymer-colloid aggregates, respectively. The revealed molecular behavior of liquid crystal dispersions may contribute to optimized synthesis of responsive liquid crystal dispersions for in-flow molecular diagnostics of polymers and colloids, and the development of functional laboratory-on-chip prototypes.

Development of a generic approach for monitoring leachable compounds in hospital pharmacy-prepared prefilled plastic packaging by ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry with postcolumn infusion

Prefilled plastic packaging is time- and cost-effective in hospital pharmacy because it prevents waste, preparation errors, dosage errors, microbial contamination and accidents. This packaging mostly includes prefilled syringes (PFS), intravenous (IV) bags and vials intended for long-term storage that can be used for immediate treatment. There is a rising availability in the market for prefilled drug products due to their practical approach. Leachable compounds could be evaluated in hospital pharmacy-prepared prefilled drug solutions. The Pharmacy Department at the Lausanne University Hospital has developed an innovative, highly sensitive, and generic method by postcolumn infusion based on ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for the analysis of plastic additives in hospital pharmacies. The postcolumn infusion solution was developed with 2% ammonium hydroxide in methanol on a representative set of 30 candidate compounds with different physical-chemical properties, such as log P and molecular structure, to represent the most important categories of additives. The LODs obtained for all compounds ranged from 0.03 to 7.91 ng/mL with linearity up to 250 ng/mL. Through this screening method, plastic additives can be rapidly identified due to the combined use of retention time, exact mass (including isotopic pattern) and MS/MS spectra. In addition, the users can screen for vast categories of plastic additives, including plasticizers, epoxy monomers, antioxidants, UV stabilizers, and others. The screening is facilitated by assessments of a complex in-house-built database for extractable and leachable trace assessment (DELTA), containing 205 compounds for unambiguous identification. Relative response factors were established for all analytes to obtain a semiquantitation of compounds. Moreover, the database also contains valuable estimative toxicology information, which was obtained through calculating their permissible dose exposure threshold; thus, estimative toxicology assessment can be performed for identified compounds in prefilled drug products. This method and the database were applied to a hospital pharmacy-prepared prefilled vancomycin syringe for paediatric use. Ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) was used to prepare the samples for leachable analysis. As a result, 17 plastic additives were formally identified, and their concentrations were estimated. A toxicology assessment was performed by comparing their concentrations with their theoretical PDE thresholds. In conclusion, the prefilled drug solution released a negligible amount of known leachables that appeared to be safe for use in neonates and children.

Nerve Injury and Peripheral Nerve Functional Loss From Injection and Suture Needles: An Experimental Study on Rats.

During invasive procedures involving needles, there is a chance of damage to peripheral nerves. Therefore, a method for experimentally simulating these situations is needed. In this study we aimed to evaluate peripheral nerve lesions caused by the entry and exit of an injection needle, nerve transfixion through a suture stitch, and the injection of saline solution and lidocaine into the nerve. After obtaining approval from the Animal Ethics Committee, we randomly divided 36 Wistar rats, weighing approximately 250 g each, into 6 groups (control, sham, suture, needle, saline, and lidocaine groups), with 6 animals in each group. All procedures were performed on the left paws of the rats. After the procedure, walking track analysis was performed to assess the walking function of rats for 8 weeks. Four months after the procedures, we performed bilateral electrophysiological studies (measuring the latency and amplitude of the electrical impulse in the peroneal nerve). Subsequently, the rats were euthanized, and bilateral tissue samples were collected from the peroneal nerve and tibialis cranialis muscle for morphometric histological analysis. In the walking track analysis, all groups showed normalization of walking functionality after 13 days. There was little histological change between the groups, and no functional loss related to the procedures was observed. Procedures involving the infusion of local anesthetic or saline solution, or suture needles, are safe with regard to peripheral nerve function loss. Accidents tend not to cause nerve impairment.

Improving the Safety of Clinical Management of COVID-19 Patients Receiving Aminoglycosides and Parenteral Nutrition: Y-site Compatibility Studies

PurposeAminoglycosides (AMGs) are broad-spectrum bactericidal antibiotics that can resolve bacterial infections co-existing with COVID-19 or exploit their potential antiviral activities. Patients presenting the most severe forms of COVID-19 due to escalating catabolism and significant lean body mass loss often require the concomitant administration of parenteral nutrition (PN) and antibiotics. The Y-site administration is one of the approaches allowing the co-administration of two intravenous medications in patients with limited vascular access. Our study aimed to investigate the compatibility of AMGs and selected commercial PN admixtures enriched in omega-3 fatty acids. MethodsGentamycin (GM), amikacin (AM), and tobramycin (TM) solutions for infusion were combined with Nutriflex Omega Special (NOS) and Smofkabiven (SFK). Three different volume ratios were investigated: 1:2, 1:1, and 2:1, simulating Y-site administration. Samples underwent visual examination and determination of the lipid emulsion particle size, zeta potential, and pH immediately after preparation and after four hours of storage at room temperature (22 ± 2 °C) with sunlight exposure. ResultsGM and AM combined with NOS in all studied ratios met the set-up acceptance criteria. The addition of TM to NOS in a 2:1 volume ratio and all tested AMGs to SFK in all studied combinations significantly influenced the stability of the oil-water system leading to the appearance of globules larger than 5 µm exceeding the pharmacopeial limit of 0.05% immediately after preparation or after four hours of storage. ConclusionIn conclusion, our study showed that NOS was less prone to destabilization of oil-in-water systems by AMGs than SFK. In justified clinical cases, due to the lack of appearance of precipitate or enlarged lipid droplets, the combined administration of GM and AM with the NOS could be considered, provided tested volume ratios of the drug and MCB in the infusion line are maintained. However, it should be noted that such an infusion may be associated with the risk of changes in the pharmacokinetics of the drug.

Sustained Effects of Capsaicin Infusion into the Oropharynx on Swallowing in Perfused Rats.

To examine the sustained effects of oropharyngeal capsaicin stimulation on the regulation of swallowing, we recorded the swallowing-related nerve activities during continuous infusion of capsaicin solution into the oropharynx. In 33 in situ perfused brainstem preparation of rats, we recorded the activities of the vagus, hypoglossal, and phrenic nerves during fictive swallowing. The interburst intervals (IBIs) of the swallowing-related nerves during sequential pharyngeal swallowing (sPSW) elicited by electrical stimulation of the superior laryngeal nerve (SLN) during concurrent capsaicin stimulation of 10, 1, and 0.1 μM (n = 28) were compared with those during oropharyngeal infusion of saline (control) (n = 5). The IBIs during SLN-induced sPSW were reduced at 5 min after initiation of continuous infusion of 10 and 1 μM capsaicin solution. The IBIs showed significant decreases to -25.8 ± 6.9%, -25.9 ± 5.3, -18.3 ± 3.7, and -12.0 ± 1.6 at 30 min following 1 μM capsaicin stimulation at SLN stimulus conditions at 5 Hz of 1.2 times threshold, 10 Hz of 40 μA, 5 Hz of 60 μA, and 10 Hz of 60 μA, respectively. Continuous capsaicin stimulation of 0.1 μM solution did not show significant sustained effects. Pharmacological stimulation of capsaicin could provide time-dependent effects on the likelihood of swallowing, particularly subserving sustained facilitation of swallowing reflex with appropriate concentration of capsaicin. NA Laryngoscope, 134:305-314, 2024.

Poly(2-ethyl-2-oxazoline)-Conjugated Hemoglobins as a Red Blood Cell Substitute.

Hemoglobin wrapped covalently with poly(2-ethyl-2-oxazoline)s (POx-Hb) is characterized physicochemically and physiologically as an artificial O2 carrier for use as a red blood cell (RBC) substitute. The POx-Hb is generated by linkage of porcine Hb surface-lysines to a sulfhydryl terminus of the POx derivative, with the average binding number of the polymers ascertained as 6. The POx-Hb shows moderately higher colloid osmotic activity and O2 affinity than the naked Hb. Human adult HbA conjugated with POx also possesses equivalent features and O2 binding properties. The POx-Hb solution exhibits good hemocompatibility, with no influence on the functions of platelets, granulocytes, and monocytes. Its circulation half-life in rats is 14 times longer than that of naked Hb. Hemorrhagic shock in rats is relieved sufficiently by infusion of the POx-Hb solution, as revealed by improvements of circulatory parameters. Serum biochemistry tests and histopathological observations indicate no acute toxicity or abnormality in the related organs. All results indicate that POx-Hb represents an attractive alternative for RBCs and a useful O2 therapeutic reagent in transfusion medicine.

Determination of binding characteristics as a measure for effective albumin using different methods

Background & aimsTransport functions of albumin are of clinical and pharmacological interest and are determined by albumin's properties like posttranslational modifications or bound ligands. Both are affected in pathological conditions and in therapeutic grade albumin solutions. The term effective albumin concentration was introduced as a measure of functionally intact albumin. Our aim was to evaluate the impact of ligands and modifications with different approaches as a measure of effective albumin. Approach & resultsWe used a spin labelled fatty acid and dansylsarcosine to characterize binding properties of albumin i) prepared from plasma of patients and healthy control donors, ii) measured directly out of plasma, iii) research grade albumin, iv) in vitro modified albumin, and v) therapeutic infusion solutions before and after removal of stabilizers.Bilirubin is the main determinant for binding function in patients' albumin. In in vitro prepared albumin bound fatty acids correlated with impaired binding. Human nonmercaptalbumin1, not human nonmercaptalbumin2, showed reduced binding properties. Binding and transport function of therapeutic albumin was severely impaired and restored by filtration. Glycation of research grade albumin had no effect on the binding of dansylsarcosine and only a minor effect on fatty acid binding. ConclusionsOur results suggest that effective albumin -in terms of binding properties- is primarily determined by bound ligands and only to a minor extent by posttranslational modifications. Characterizing albumin directly from plasma better reflects the physiological situation whereas in the case of therapeutic grade albumin stabilizers should be removed to make its binding properties accessible.

Adrenaline-resistant anaphylactic shock caused by contrast medium in a patient after risperidone overdose: a case report

BackgroundIn Japan, the use of risperidone in combination with adrenaline is contraindicated, except in cases of anaphylaxis. Therefore, there is limited clinical evidence regarding the interaction of these two drugs. Here, we report the clinical course of a case of adrenaline-resistant anaphylactic shock induced by a contrast medium injection after a risperidone overdose.Case presentationA man in his 30s was transported to our hospital after attempting suicide by taking 10 mg of risperidone and jumping from a height of 10 m. To determine the location and severity of his injuries, he was injected with an iodinated contrast medium, after which he developed generalized erythema and hypotension and was diagnosed with anaphylactic shock. A 0.5 mg dose of adrenaline was administered with no improvement, followed by another 0.5 mg dose that did not change his blood pressure. After infusion of a sodium bicarbonate solution (8.4%), administration of fresh frozen plasma, and additional administration of adrenaline (0.6–1.2 µg/min), his blood pressure improved, and he recovered from the anaphylactic shock.ConclusionsThis was a rare case of a risperidone overdose followed by adrenaline-resistant anaphylactic shock. The resistance is likely associated with the high blood concentration of risperidone. Our findings indicate that the potential for decreased adrenergic responsiveness should be considered in patients undergoing risperidone treatment in the event of anaphylactic shock.

Assessment of Hyperosmolar Blood-Brain Barrier Opening in Glioblastoma via Histology with Evans Blue and DCE-MRI.

While the blood-brain barrier (BBB) is often compromised in glioblastoma (GB), the perfusion and consequent delivery of drugs are highly heterogeneous. Moreover, the accessibility of drugs is largely impaired in the margins of the tumor and for infiltrating cells at the origin of tumor recurrence. In this work, we evaluate the value of methods to assess hemodynamic changes induced by a hyperosmolar shock in the core and the margins of a tumor in a GB model. Osmotic shock was induced with an intracarotid infusion of a hypertonic solution of mannitol in mice grafted with U87-MG cells. The distribution of fluorescent dye (Evans blue) within the brain was assessed via histology. Dynamic contrast-enhanced (DCE)-MRI with an injection of Gadolinium-DOTA as the contrast agent was also used to evaluate the effect on hemodynamic parameters and the diffusion of the contrast agent outside of the tumor area. The histological study revealed that the fluorescent dye diffused much more largely outside of the tumor area after osmotic shock than in control tumors. However, the study of tumor hemodynamic parameters via DCE-MRI did not reveal any change in the permeability of the BBB, whatever the studied MRI parameter. The use of hypertonic mannitol infusion seems to be a promising method to increase the delivery of compounds in the margins of GB. Nevertheless, the DCE-MRI analysis method using gadolinium-DOTA as a contrast agent seems of limited value for determining the efficacy of opening the BBB in GB after osmotic shock.

Physical compatibility of ibuprofen and selected parenteral drugs during simulated y-site administration

Intravenous ibuprofen (IBF) is indicated for short-term acute moderate pain and fever management. Limited data concerning the compatibility of intravenous IBF and other parenteral medications makes it inconvenient to use in polypharmacy-required patients. The simultaneous administration of two incompatible drugs is a health- or even life-threatening medical error. This study was performed to evaluate the physical compatibility of two intravenous IBF doses (600 mg/100 mL, 400 mg/100 mL) during Y-site administration with common parenteral medications. Eight infusion fluids, seven ready-to-use solutions for infusion, and thirty concentrates or powders for solutions for infusion were examined. All these drugs, if relevant, were reconstituted and diluted following the manufacturer's instructions to achieve concentrations found most commonly in clinical practice. Samples were prepared by mixing IBFs and selected drug product solutions at the 1:1 volume ratio. All samples underwent visual inspection and determination of pH and turbidity before combining with IBF and in time points (0, 30, 60, and 120 minutes) after simulated Y-site administration with IBF. In the case of propofol, which is an emulsion for infusion, lipid droplet size, zeta potential, and polydispersity index were also determined. The incompatibilities were observed for IBF combinations with amiodarone, ciprofloxacin, clemastine, gentamicin, vinpocetine, and calcium chloride.

Meglumine Sodium Succinate in Diabetic Ketoacidosis

The most common agent used for infusion therapy in patients with diabetic ketoacidosis (DKA) is isotonic 0.9% sodium chloride solution. However, infusion of required volumes can result in development of iatrogenic complications — i. e., worsening of metabolic hyperchloremic acidosis in DKA patients with already altered acid-base balance. Balanced crystalloid solutions can be used as alternative to saline.Objective. To evaluate the feasibility of using meglumine sodium succinate (MSS) balanced crystalloid solution in DKA.Material and methods. We examined 2 groups of patients, 30 subjects each, with moderate and severe diabetic ketoacidosis admitted to anesthesiology and intensive care unit. Patients from both groups were administered with insulin and an infusion therapy was employed according to current clinical guidelines for the management of patients with complications of diabetes mellitus. In the comparison group, infusion therapy included 0.9% sodium chloride, 4% potassium chloride, and 5% dextrose. In the study group MSS intravenous drip infusions 10 ml/kg/daily were added to the infusion protocol. Volumes and infusion rates were comparable in both groups. The following indicators were evaluated: time to resolution and DKA resolution rates during thorough monitoring (first 48 hours of therapy), the time (in hours) before discontinuation of insulin infusion; the time to complete consciousness recovery (15 items on the Glasgow Coma scale); the duration (in hours) of stay in the intensive care unit (ICU), dynamics of blood electrolytes; parameters of acid-base balance; levels of glycemia and lactatemia.Results. All patients improved and were transferred from ICU, the mortality rate was 0%. Infusion of MSS shortened the time to DKA resolution (30.0 h [24.0 h; 36.0 h] in the study group, vs 44.5 h [36.5 h; 51.5 h] in the comparison group (P=0.001)); DKA resolution rates during 48 hours from initiation of therapy achieved 90.0% (27) in the study group, vs 66.7% (20) in the comparison group (P=0.060)); duration of intravenous insulin infusion was 32.0 h [24.5 h; 40.0 h] in the study group vs 48.0 h [40.0 h; 55.5 h] in the comparison group (P=0.001)); duration of ICU stay was 41.0 h [30.0 h; 48.0 h] in the study group, vs 56.0 h [50.0 h; 66.3 h] in the comparison group (P=0.001).Conclusion. Infusion of a balanced succinate-containing crystalloid solution improves the results of DKA treatment, as compared to traditional infusion of 0.9% sodium chloride.

Modification of peripheric Treg and CD56brightNK levels in RIF women after egg donation, treated with GM-CSF or placebo

Recurrent implantation failure (RIF) is defined as when implantation repeatedly failed to reach a stage recognizable by pelvic ultrasound in IVF cycle and it may be due to several causes. The GM-CSF is a cytokine promoting leukocyte growth and trophoblast development: we tested it to treat these patients in a pilot-controlled trial evaluating the modification of peripheric Treg and CD56brightNK levels after the treatment with this cytokine and in control patients affected by RIF after egg donation cycles. This study was performed on 24 RIF women after egg donation cycles. Single good quality blastocyst transfer was performed in the cycle object of this study. Patients were randomly assigned to two groups: 12 women treated with subcutaneous GM-CSF 0.3 mg/kg/daily from the day before embryo transfer to the β-hCG day, and 12 women treated with subcutaneous saline solution infusion as control. All patients were tested for Treg and CD56brightNK cell levels in blood circulation before and after treatment using flow-cytometry with specific antibodies. The two groups of patients were similar for epidemiologic characteristics, the ongoing pregnancy rate in the GM-CSF group was 83.3% whereas in the control group was 25.0% (P = 0.0123). In the study group there was a significative increase of Treg cells (P < 0.001) with respect to the levels before treatment and to control group. Instead, the levels of CD56brightNK did not show any significative variation. Our study showed that the treatment with GM-CSF increases the Treg cells in the peripheric blood.

#4015 RECOMBINANT HIGH-DENSITY LIPOPROTEIN MODULATES INFLAMMATORY RESPONSE AND RENAL DYSFUNCTION IN A SWINE MODEL OF SEPSIS-INDUCED ACUTE KIDNEY INJURY

Abstract Background and Aims Sepsis is a severe and dysregulated inflammatory disease that often precedes the development of acute kidney injury (AKI) with consequent worsening outcome. Although clinical data demonstrate that high-density lipoprotein (HDL) levels drop in septic patients with a poor prognosis, little is known about the molecular basis of HDL's role in systemic inflammation and renal function. Here we investigate the possible effects of a novel engineered HDL-mimetic (CER-001) in a swine model of lipopolysaccharide (LPS)-induced AKI. Method Sepsis was induced by intravenous infusion of a saline solution containing 300 μg/kg of LPS in a porcine model. The animals were randomized into three groups: LPS (endotoxemic pigs, n = 6), CER20 (endotoxemic pigs treated with a single dose of CER-001 20mg/kg; n = 6), and CER20 × 2 (endotoxemic pigs treated with two doses of CER001 20mg/kg; n = 6). Animals were sacrificed after 24h from the start of experimental procedure. Renal histologic and biochemical changes were analyzed. Endothelial dysfunction biomarkers, circulating pro-inflammatory mediators, LPS and Apolipoprotein A-I (Apo A-I) levels were quantified with ELISA assay. Systemic complement activation was evaluated by Wieslab kit. Results Untreated animals were highly susceptible to LPS challenge and usually succumbed before completing the study protocol (LPS group 16.7%). CER-001 treatment increased the survival rate of endotoxemic pigs, compared to the LPS group (CER20, 50%; CER20 × 2, 66.7%). Furthermore, as shown in Figure 1A, LPS injection led to a time-dependent increase of IL-6 in endotoxemic animals respect to basal condition (T0). CER-001 treatment was able to reverse LPS effects. In particular, the second infusion of CER-001 three hours after the first dose (T3) strongly reduced IL-6 serum levels back to basal level (LPS p &amp;lt;0.05). Similarly, we found high levels of TNF-α and MCP-1 in endotoxemic pigs that were significantly decreased in both CER-001 treatment arms (T24, CER20 × 2 vs LPS group, IL-6, p = 0.0086; TNF-α, p&amp;lt;0.0001; MCP-1, p = 0.0009). In addition, CER-001 treatment ameliorated systemic endothelial dysfunction by reducing VCAM and ICAM serum levels. A significant activation of classical and alternative complement pathway (vs T0 p &amp;lt;0.05) was observed at 1h, 3h and 24h after LPS infusion. CER001 treatment significantly prevented systemic complement activation in both treated groups (vs LPS p &amp;lt;0.05). We also investigated whether CER001 infusions significantly prevented renal tissue damage. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; CER-001 treatment preserved renal parenchyma, recovered urine output, decreased creatine levels, and reduced the biomarkers of tubular damage, Cystatin C and KIM-1, both in serum and urine samples. Considering that HDL has a very high affinity for LPS, we evaluated the circulating LPS concentration in treated animals. We observed that LPS levels were greatly reduced in treated animals and the effects are more evident after the second infusion of CER-001(Figure 1B). Therefore, we also examined LPS levels in bile samples and we observed a dose-dependent increasing amount of endotoxin in the CER001 treated septic pigs. Conclusion This preclinical data indicates that CER001 treatment prevents systemic inflammation thereby limiting renal damage. The mechanism of action is two-fold consisting of both the scavenging of endotoxin and a direct anti-inflammatory effect of CER-001.

#6078 MODULATION OF TRYPTOPHAN METABOLISM IN SEPSIS-INDUCED ACUTE KIDNEY INJURY (AKI): A NEW THERAPEUTIC APPROACH TO PREVENT NEUROCOGNITIVE IMPAIRMENT

Abstract Background and Aims Partial recovery following AKI could lead to long-term consequences that predispose to chronic dysfunction and may also accelerate progression of neurocognitive impairment. In this scenario, a tight crosstalk between kidney and brain named “kidney-brain axis” seems to play a pivotal role leading to detrimental outcome for AKI patients. Notably, many studies suggest a high relationship between kidney damage and brain dysfunction (cognitive impairment, taste and olfactory dysfunction, peripheral nerve dysfunction) even after the resolution of AKI. Furthermore, patients who suffered AKI may afterward show a disturbance of arousal, also called “brain fog”. Although major advances have been made in our understanding of the pathophysiology of AKI and brain dysfunction, there are no available preventive and therapeutic strategies in this field. Recent findings have revealed remarkable link existing between dyslipidemia/low High-density lipoprotein (HDL) levels and Kynurenine pathway (KP) alterations that lead to the production of neuroactive metabolites such as kynurenine (KYN) and quinolinic acid (QA) in AKI setting. Method Sepsis-induced AKI (SI-AKI) was induced in a porcine model by intravenous infusion of a saline solution containing 300 μg/kg of LPS. After LPS injection, 12 animals were treated with different doses of recombinant HDL (rHDL) (20–40 mg/kg) (rHDL group), while 6 animals did not receive treatment (LPS group). Animals were sacrificed after 24h from the start of experimental procedure. Results Endotoxemic pigs developed oliguric AKI with increased tubular and glomerular damage and interstitial inflammatory infiltrate. We found that rHDL treatment significantly decreased the inflammatory process and tubular damage, preventing AKI, especially in the rHDL 40 mg/kg group. Then, we evaluated the Indolamine-2,3-dioxygenase 1 (IDO1) enzyme activation, which is the first and rate-limiting step of KP, upregulated during inflammation in both sera and brain tissue, and has been linked to cognitive dysfunction. In our model, LPS induced an increased activation of the IDO-1 gene expression at brain level in endotoxemic animals, meanwhile it appears to be reduced in both treated arms (p&amp;lt;0.005). Furthermore, sera from the rHDL group showed a significant reduction in IDO1 activity (KYN/Trp ratio) (p&amp;lt;0.05) and QA levels (p&amp;lt;0.005) compared with the LPS group. Moreover, a significant decrease of both systemic and brain IL-6 levels was observed after rHDL treatments. Conclusion Our preliminary data indicated that HDL-enhancing therapies may decrease the inflammatory response, the retention of waste products and neuroactive compounds, improving renal and cognitive function in SI-AKI.

High-pressure infusion improves multi-territory perforator flap viability via choke artery dilation: A preliminary study in a rat model

Multi-territory perforator flaps have become the preferred option for the repair and reconstruction of large soft tissue defects. Although methods (e.g., pharmacological agents, mechanical stimulation, and thermal stimulation) were developed to open choke vessels to improve flap survival, the flap necrosis rate is still as high as 28.8%. The authors hypothesized that high-pressure infusion might enhance flap viability by dilating choke arteries intraoperatively in a rat model of multi-territory perforator flap. Two-month-old male Sprague-Dawley rats were randomized into two groups (n=32 each). During the multi-territory perforator flap elevation based on the right superficial epigastric angiosome, one group received continuous high-pressure infusion (mean pressure, 250mmHg; duration, 1min) of an isotonic heparin sodium solution (12,500U/L) via the artery in the pedicle, whereas the other group received no infusion. At 7 days postoperatively, arteriography was performed; endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) expression and microvascular density were evaluated by western blot and histology, respectively; and flap survival was compared. Moreover, intraluminal diameters were examined at 1day and 7 days postoperatively using hematoxylin and eosin staining, and coagulation function was assessed immediately postoperatively. High-pressure infusion significantly promoted the dilation of choke arteries at 1day and 7 days postoperatively. It also increased eNOS and VEGF expression, flap survival, and microvascular density. The coagulation function remained unaffected. High-pressure infusion allowed intraoperative and postoperative dilation of the choke arteries that enhanced the viability of multi-territory perforator flaps in rats.

Chemical pancreatectomy in non-human primates ablates the acini and ducts and enhances beta-cell function

Chronic pancreatitis is a debilitating disease affecting millions worldwide. These patients suffer from bouts of severe pain that are minimally relieved by pain medications and may necessitate major surgeries with high morbidity and mortality. Previously, we demonstrated that “chemical pancreatectomy,” a pancreatic intraductal infusion of dilute acetic acid solution, ablated the exocrine pancreas while preserving the endocrine pancreas. Notably, chemical pancreatectomy resolved chronic inflammation, alleviated allodynia in the cerulein pancreatitis model, and improved glucose homeostasis. Herein, we extensively tested the feasibility of a chemical pancreatectomy in NHPs and validated our previously published pilot study. We did serial computed tomography (CT) scans of the abdomen and pelvis, analyzed dorsal root ganglia, measured serum enzymes, and performed histological and ultrastructural assessments and pancreatic endocrine function assays. Based on serial CT scans, chemical pancreatectomy led to the loss of pancreatic volume. Immunohistochemistry and transmission electron microscopy demonstrated exocrine pancreatic ablation with endocrine islet preservation. Importantly, chemical pancreatectomy did not increase pro-nociceptive markers in harvested dorsal root ganglia. Also, chemical pancreatectomy improved insulin secretion to supranormal levels in vivo and in vitro. Thus, this study may provide a foundation for translating this procedure to patients with chronic pancreatitis or other conditions requiring a pancreatectomy.

Stability of nafamostat in intravenous infusion solutions, human whole blood and extracted plasma: implications for clinical effectiveness studies.

Aim: To describe the stability of nafamostat in infusion solutions, during blood sample collectionand in extracted plasma samples in the autosampler. Methods: Nafamostat infusion solutions were stored at room temperature in the light for 24h. For sample collection stability, fresh blood spiked with nafamostat was subjected to combinations of anticoagulants, added esterase inhibitor and temperature. Nafamostat was monitored in the extracted plasma samples in the autosampler. Results: Nafamostat was stable in infusion solutions. Nafamostat in whole blood was stable for 3h before centrifugation when collected in sodium fluoride/potassium oxalate tubes (4°C). Nafamostat in extracted plasma samples degraded at 4.7±0.7% per h. Conclusion: Viable samples can be obtained using blood collection tubes with sodium fluoride, chilling and processing promptly.

Abomasal infusion of oleic acid and exogenous emulsifier alter fatty acid digestibility and production responses of lactating dairy cows

We evaluated the effects of abomasal infusion of cis-9 C18:1 (oleic acid) and an exogenous emulsifier (polysorbate-C18:1) on fatty acid (FA) digestibility and production responses of dairy cows. Eight rumen-cannulated multiparous cows (96 ± 23 d in milk) were assigned to a 2 × 2 factorial arrangement of treatments in 4 × 4 Latin squares with 18-d periods consisting of 7 d of washout and 11 d of infusion. Treatments were abomasal infusions of water carrier only (CON), 45 g/d oleic acid (OA), 20 g/d polysorbate-C18:1 (T80), or both 45 g/d OA and 20 g/d T80 (OA+T80). The OA treatments were dissolved in ethanol and the T80 treatments in water. To deliver the daily dose for each treatment, the infusate solution was divided into 4 equal infusions per day, occurring every 6 h. Cows were fed the same diet, which contained [% of dry matter (DM)] 30.3% neutral detergent fiber (NDF), 16.3% crude protein, 30% starch, and 3.2% FA (including 1.8% DM from a FA supplement containing 34.4% C16:0 and 47.7% C18:0). Infusion of T80 increased NDF digestibility compared with all other treatments (3.57 percentage units), whereas OA+T80 decreased NDF digestibility compared with CON (3.30 percentage units). Compared with CON, OA (4.90 percentage units) and T80 (3.40 percentage units) increased total FA digestibility, whereas OA+T80 had no effect on total FA digestibility. We did not observe differences between OA and T80 for total FA digestibility. Infusion of OA (3.90 percentage units) and T80 (2.80 percentage units) increased 16-carbon FA digestibility compared with CON. Digestibility of 16-carbon FA did not differ between OA and T80 or between CON and OA+T80. Compared with CON, OA increased (5.60 percentage units) and T80 tended to increase 18-carbon FA digestibility. Digestibility of 18-carbon FA did not differ between OA and T80 or between CON and OA+T80. Compared with CON, all treatments increased or tended to increase the absorption of total and 18-carbon FA. Infusion of OA and T80 increased the yields of milk fat (both increased 0.10 kg/d), 3.5% fat-corrected milk (1.90 and 2.50 kg/d), and energy-corrected milk (1.80 and 2.60 kg/d) compared with CON. We did not observe differences between OA and T80 or between CON and OA+T80 for yields of milk fat, 3.5% fat-corrected milk, or energy-corrected milk. Infusing OA tended to increase plasma insulin concentration compared with CON. Compared with the other treatments, OA+T80 decreased the yield of de novo milk FA (31.3 g/d). Compared with CON, OA tended to increase the yield of de novo milk FA. Compared with OA+T80, CON and OA tended to increase the yield of mixed milk FA, whereas T80 increased it (83 g/d). Compared with CON, all emulsifier treatments increased the yield of preformed milk FA (52.7 g/d). In conclusion, abomasally infusing either 45 g of OA or 20 g of T80 improved digestibility and similarly favored the production parameters of dairy cows. In contrast, providing both (45 g of OA + 20 g of T80) had no additional benefits and moderated the positive responses observed in the individual treatments with OA and T80.

Mitigation of post breeding endometritis in mares treated with platelet rich plasma

Persistent breeding-induced endometritis (PBIE) is one of the major causes of infertility in mares, characterized by a lingering inflammatory response in the uterus, which leads to accumulation of uterine fluid and polymorphonuclear cells (PMN), harming the reproductive efficiency of the animal. The aim of this study was to determine if the presence and volume of intrauterine fluid and the percent of endometrial neutrophils decreased after intrauterine application of blood platelet-rich plasma (PRP) in mares with post-mating endometritis. Healthy estrous crossbreed mares (n = 9) aged between 6 to 12 years, with optimal body condition and under the same nutritional management, had two cycles randomly assigned to a crossover trial. Each received either intrauterine infusions of lactate ringer solution (LRS) or autologous PRP 4h after artificial insemination (AI) with fresh semen of low sperm quality from the same stallion. All the animals went through all the treatments. A total of 100 mL of citrated whole blood was collected for PRP production and was centrifuged at 2315g for 15 minutes then 579g for 10 minutes. The presence of intrauterine fluid (IUF) was analyzed by ultrasonographic examination and the percentage of endometrial neutrophils was determined through endometrial cytology, both before insemination (in the presence ofa preovulatory follicle ≥35mm and endometrial edema) and 24h after treatment application. Statistical analysis was performed by a Mixed model (SAS, 2023) for repeated measures with treatment and time as between subject factors. The presence of intrauterine fluid had an effect of time (p ≤ 0.049), where fluid size was smaller before AI than 24h after treatment; however, there was no treatment effect (p ≥ 0.264) over intrauterine fluid. The percentage of endometrial neutrophils had an effect of time (p ≤0.001), less inflammatory cells were found before AI than 24 hours after treatment; there was an effect of treatment (p ≤0.001) as well, where PRP decreased the number of endometrial polymorphonuclear cells compared to the control group infused with LRS. The increase in intrauterine fluid with time suggests that semen itself increases blood perfusion that generates intrauterine fluid accumulation. After induction of physiological endometritis, endometrial polymorphonuclear cell numbers were reduced successfully with PRP treatment. PRP is rich in peptides and signaling proteins that suppress the expression of proinflammatory cytokines such as IL-1 and TNF, inhibits polymorphonuclear neutrophil migration, and thus regulates intrauterine inflammation through decreased endometrial COX-2 expression.