Local Infusion Research Articles

Methionine Sulfoximine as a Tool for Studying Temporal Lobe Epilepsy: Initiator, Developer, Attenuator.

Methionine sulfoximine (MSO) is a compound originally discovered as a byproduct of agene-based milled flour maturation. MSO irreversibly inhibits the astrocytic enzyme glutamine synthase (GS) but also interferes with the transport of glutamine (Gln) and of glutamate (Glu), and γ-aminobutyric acid (GABA) synthesized within the Glu/Gln-GABA cycle, in this way dysregulating neurotransmission balance in favor of excitation. No wonder that intraperitoneal administration of MSO has long been known to induce behavioral and/or electrographic seizures. Recently, a temporal lobe epilepsy (TLE) model based on local continuous infusion of MSO into the hippocampus has been developed reproducing the main features of human mesial TLE: induction of focal seizures, their spreading, increase in intensity over time, and development of spontaneous recurrent seizures. Fully developed TLE in this model is associated with hippocampal degeneration, hallmarked by reactive astrogliosis, and causally related to the concomitant loss of GS-containing astrocytes. By contrast, short-term pre-exposure of rats to relatively low MSO doses that only moderately inhibited GS, attenuated and delayed the initial seizures in the lithium-pilocarpine model of TLE and in other seizure-associated contexts: in the pentylenetetrazole kindling model in rat, and in spontaneously firing or electrically stimulated brain slices. The anti-initial seizure activity of MSO may partly bypass inhibition of GS: the postulated mechanisms include: (i) decreased release of excitatory neurotransmitter Glu, (ii) prevention or diminution of seizure-associated brain edema, (iii) stimulation of glycogenesis, an energy-sparing process; (iv) central or peripheral hypothermia. Further work is needed to verify either of the above mechanisms.

Regional nerve block in postoperative analgesia after cesarean section: A narrative review

Of all obstetric operations, cesarean section is one of the most common. The impact of postoperative pain on physical and mental health in women cannot be ignored. Moreover, effective postoperative analgesia is essential in women who have given birth. Traditional systemic analgesic methods (intravenous analgesia, oral analgesics, etc) are often accompanied by adverse reactions that are positively correlated with the drug dosage. Regional nerve block is an analgesic and anesthetic technique that temporarily blocks nerve conduction by injecting local anesthetics around the nerve roots, nerve trunks, nerve plexus, ganglia, or surgical area, thereby alleviating or eliminating pain. Currently, the regional block techniques used for postoperative analgesia following cesarean section include paravertebral nerve block, transversus abdominis plane block, rectus sheath block, quadratus lumborum block, ilioinguinal-iliohypogastric nerve block, erector spinae block, wound infiltration analgesia, and intraperitoneal infusion of local anesthetics. These regional block techniques hold great promise for providing effective postoperative analgesia after cesarean section, each with unique advantages. Moreover, regional blocks have a unique place in multimodal analgesia protocols following cesarean section and are increasingly used in clinical practice for analgesia after cesarean section. This review provides an overview of the regional nerve block techniques used for postoperative analgesia following cesarean section, discusses their benefits and drawbacks, and provides a reference for choosing postoperative pain management following cesarean delivery, offering a hopeful outlook for improved patient care.

Agonists of the opioid δ-receptor improve irritable bowel syndrome-like symptoms via the central nervous system.

Irritable bowel syndrome (IBS) is a common condition that is challenging to treat, and novel drugs are needed for this condition. Previously, a chronic vicarious social defeat stress (cVSDS) mouse model exhibits IBS-like symptoms. Also agonists of the opioid δ-receptor exert anti-stress effects in rodents with minimal adverse effects. Here, we evaluated the effects of δ-receptor agonists on the IBS-like symptoms in cVSDS mice. cVSDS mice (male C57BL/6J mice) were prepared following a 10-day exposure to witness of social defeat stress. Subsequently, intestinal peristaltic motility and abdominal hyperalgesia were evaluated using the charcoal meal test (CMT) and capsaicin-induced hyperalgesia test (CHT), respectively. Extracellular glutamate levels were measured using in vivo brain microdialysis. The drug was singly administrated 30 min before testing. In cVSDS mice, systemic (10 mg kg-1) and intracerebroventricular (30 nmol) administration of a δ-receptor agonist regulated intestinal peristalsis in the CMT and relieved abdominal pain in the CHT. Effects of systemic administration were blocked by intracerebroventricular injection of a δ-receptor inhibitor. Local infusion of the δ-receptor agonist (0.6 nmol) into the insular cortex improved cVSDS-induced intestinal hypermotility. The in vivo brain microdialysis study showed that re-exposure to VSDS elevated the extracellular glutamate levels in the IC, which was restored by the δ-receptor agonist. We propose that agonists of opioid δ-receptors are potential drugs for the radical treatment of IBS because they can ameliorate IBS-like symptoms via the CNS, specifically the insular cortex.

The Role of Transarterial Embolization Plus Radiotherapy Compared to Radiotherapy or Transarterial Embolization Alone in the Management of Painful Bone Metastases: Results of a Systematic Review.

This study systematically reviews the efficacy and safety of combining transarterial embolization (TAE) with radiotherapy (RT) for managing bone metastases (BM), assessing clinical response (CR), and local control (LC). A literature search using PubMed, Scopus, Web of Science, Medline Plus, and the Cochrane Library identified three relevant studies with 74 patients and 103 BM. One study included local chemotherapy infusion with TAE. All studies reported CR rates, though one used skeletal-related events as a surrogate, while only one study provided LC rates. Adverse events were noted across all studies. A quantitative analysis of CR rates showed a relative risk (RR) of 0.15 (confidence interval (CI): 0.03-0.69) favoring TAE plus RT over RT alone, while no significant differences were observed between TAE plus RT and TAE alone (RR: 0.91; CI: 0.51-1.63). The combined TAE and RT approach demonstrated effectiveness in local tumor control and produced faster, longer-lasting pain relief than RT alone, although TAE was associated with a mild, transient increase in side effects. While TAE plus RT shows potential benefit and acceptable toxicity, the current evidence is of low quality.

Coiling of echogenic perineural catheters with integral stylet: A proof-of-concept randomized control trial in a sciatic nerve block simulator and a pilot study in orthopaedic-trauma patients.

We investigated a technique that facilitates the coiling of a regular straight catheter (with integral stylet) behind the sciatic nerve in an ultrasound (US) regional anaesthesia simulator, and then applied our findings to a series of orthopedic-trauma patients. We conducted a randomized study of two methods of perineural catheter advancement in a sciatic nerve block Blue Phantom simulator. Two groups of twenty catheters each (method A and method B) were evaluated under real-time ultrasound imaging. The needle in-plane/nerve in-short-axis technique was applied. In method A the catheter was advanced beyond the needle tip with the integral stylet extending along its entire length; in method B the catheter was advanced after its integral stylet was retracted by 6 cm, thus providing flexibility to the catheter's distal end. Additionally, to assess the procedural effectiveness of method B coiling technique, a pilot study was conducted examining 25 perineural catheters coiled underneath the sciatic nerve in trauma-orthopaedic patients to document any catheter tip displacement from their initial position (for 36 hours postoperatively). In the simulation study, method B led to a significantly higher percentage (18/20:90%) of coiled catheters than method A (3/20:15%). Two coiled catheters of method B were found kinked/obstructed. In our patients, after catheter insertion, the distal end of 2/25 (8%) coiled catheters was obstructed. One perineural catheter was dislodged. For the remaining 22 (88%) catheters, ultrasound imaging demonstrated that local anaesthetic infusion made contact with the sciatic nerve, indicating no displacement of the catheter's distal end postoperatively. Regular straight perineural catheters can be coiled if their integral stylet is partially retracted. This coiling method offers extra catheter length adjacent to the nerve structure which potentially mitigates catheter tip displacement. clinicaltrials.gov, registration No: NCT06568510, 23/08/2024, registration URL: https://clinicaltrials.gov/study/NCT06568510?intr=coiling%20of%20echogenic%20sciatic%20nerve&rank=1#study-overview.

Modulation of cutaneous vasodilation by reactive oxygen species during local and whole body heating in young and older adults.

We evaluated reactive oxygen species (ROS) modulation of cutaneous vasodilation during local and whole body passive heating in young and older adults. Cutaneous vascular conductance normalized to maximum vasodilation (%CVCmax) was assessed in young and older adults (10/group) using laser-Doppler flowmetry at four dorsal forearm sites treated with 1) Ringer solution (control), 2) 100 µM apocynin (NADPH oxidase inhibitor), 3) 10 µM allopurinol (xanthine oxidase inhibitor), or 4) 10 µM tempol (superoxide dismutase mimetic), via intradermal microdialysis during local (protocol 1) and whole body heating (protocol 2). In protocol 1, forearm skin sites were set at 33°C during baseline and then progressively increased to 39°C and 42°C (30 min each). In protocol 2, participants were immersed in warm water (35°C, midsternum) with the experimental forearm above water level, and local skin sites were maintained at 34°C. Bath temperature was increased (∼40°C) to clamp core temperature at 38.5°C for 60 min. In protocol 1, there were significant treatment site by age interactions for the 39°C (P = 0.015) and 42°C (P = 0.004) plateaus; however no significant effects were observed after post hoc adjustment. In protocol 2, there was a significant treatment site by age interaction (P < 0.001), where %CVCmax in older adults was 11.0% [7.4, 14.6] higher for apocynin (P < 0.001), 8.9% [5.3, 12.5] higher for allopurinol (P < 0.001), and 4.8% [1.3, 8.4] higher for tempol (P = 0.016) sites relative to the control site. ROS derived from NADPH oxidase and xanthine oxidase attenuate cutaneous vasodilation in older adults during passive whole body heating, but not during local skin heating, with negligible effects on their young counterparts for either heating modality.NEW & NOTEWORTHY We found that local infusion of apocynin or allopurinol improved cutaneous vasodilator responses to passive whole body heating (but not local skin heating) in healthy older adults. These findings indicate that impaired microvascular responses to whole body heating with primary aging are linked to augmented production of reactive oxygen species (ROS) from NADPH oxidase and xanthine oxidase. This study sheds new light on the specific ROS pathways that modulate age-related changes in cutaneous microvascular responses to heating.

HPB SO34 - Inter-fascial/Wound Catheter with Local Anaesthetic Infusion vs Thoracic Epidural Analgesia in Hepato-biliary Surgery (HILA) – A Retrospective Cohort Study

Abstract Background Thoracic epidural analgesia (TEA) offers effective pain control after open hepato-biliary surgery, however it is associated with several limitations that delay post-operative recovery. This study compared outcomes between inter-fascial/wound catheter with local anaesthetic infusion (IF/WC) and thoracic epidural analgesia (TEA) following open liver and biliary surgery in an enhanced recovery after surgery (ERAS) setting. Method Retrospective cohort data of all open liver and biliary surgery between August 2023 to February 2024 that used inter-fascial/wound catheter with local anaesthetic infusion (IF/WC) or thoracic epidural analgesia (TEA). Baseline characteristics were similar in the combined IF (n=17) and WC (n=7) group vs TEA (n=39) group. Technical failure rates were 12.5% in the IF/WC group vs 20.5% in the TEA group, p=0.509. Results Vasopressor requirement immediately post-surgery decreased by 32.7% in IF/WC vs TEA group [8.3% vs 41.0%, p=0.005], whereas none in the IF/WC group required vasopressor beyond 24 hours [0 vs 25.6%, p=0.010]. Length of critical care stay reduced by 1.5 days [1.79 vs 3.28 days; 95% CI 0.28-2.70, p=0.016] while length of hospital stay reduced by 2.6 days [5.79 vs 8.41 days; 95% CI 0.72-4.52, p=0.022] in the IF/WC vs TEA group. Admission cost reduced by £3941 per patient in the IF/WC vs TEA group [£10323 vs £14265; 95% CI 661-7222, p=0.019]. Conclusion Inter-fascial/wound catheter with local anaesthetic infusion (IF/WC) is an effective, safe and cost-saving alternative to thoracic epidural analgesia (TEA) with significant decrease in post-operative vasopressor requirements, and length of critical care and hospital stay.

VS 02 - HPB Inter-fascial Catheter with Local Anaesthetic Infusion in Hepato-biliary Surgery (HILA) – A Video Guide to Catheter Placement

Abstract Background Thoracic epidural analgesia (TEA) offers effective pain control after open hepato-biliary surgery, however it is associated with several limitations that delay post-operative recovery. Inter-fascial catheter with local anaesthetic infusion (IF) is an effective, safe and cost-saving alternative to thoracic epidural analgesia (TEA) following open liver and biliary surgery, with significant decrease in post-operative vasopressor requirements, and length of critical care and hospital stay. Method This video presentation outlines current clinical evidence with local data from Nottingham University Hospital, relevant clinical anatomy of the inter-fascial plane, intra-operative placement techniques, tips and tricks as well as troubleshooting in the event of a catheter related complication. Results The inter-fascial catheters can be placed in the transversus abdominis or posterior rectus plane based on the type of skin incision to achieve optimal post-operative pain control. It is associated with a low technical failure rate. Conclusion Inter-fascial catheter with local anaesthetic infusion is an effective, safe and cost-saving technique associated with significant decrease in post-operative vasopressor requirement, and length of critical care and hospital stay.

Abstract 4135869: Local Ethanol Infusion after Pulsed Field Ablation Enhances Acute Efficacy of In Vivo Ventricular Electroporation

Background: Pulsed field ablation (PFA) has emerged as an innovative technology for treating cardiac arrhythmias. PFA increases cell permeability, which can lead to apoptosis. Greater PFA energy may be necessary to ablate ventricular myocardium for ventricular tachycardia circuits, but this carries risks of side effects such as gaseous formation (microbubbles) and hemolysis. Ethanol (EtOH) infusion has been used to ablate pathologic myocardial tissues in hypertrophic cardiomyopathy and for refractory arrhythmias. Hypothesis: We hypothesize that PFA in the ventricle can increase EtOH uptake through PFA-generated pores, thereby enhancing ablation efficacy, even at low powers, by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effect of local EtOH infusion after PFA on lesion size in porcine ventricles. Methods: The ventricles of five porcine subjects were ablated in vivo with a PFA low power setting (750 V, at 20 μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA was performed, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared the electrograms voltage amplitude reduction before and after PFA, and the ablation lesion characteristics. Results: A total of 10 lesions in the control group and 9 lesions in the EtOH group were analyzed. For the controls, the voltage after PFA was not reduced. In contrast, for the EtOH group, the voltage after PFA was significantly reduced ( Figure 1A ). On gross pathology, there were significant differences in ablation lesion depths and volumes between the 2 lesion sets ( Figure 1A-B ). Conclusion: Local EtOH infusion after ventricular PFA enhanced acute efficacy of electroporation. Concurrent PFA with local EtOH infusion has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Future studies on chronic efficacy are warranted.

Spinal analgesia with continuous local wound infusion vs thoracic epidural analgesia after open pancreaticoduodenectomy.

The current gold standard for postoperative analgesia following a pancreaticoduodenectomy (PD) is a thoracic epidural analgesia (TEA). Spinal analgesia with continuous wound infusion (CWI) of local anaesthetic is an emerging alternative modality. This non-inferiority study aimed to compare CWI with spinal analgesia to TEA and assess its impact on clinical outcomes. A retrospective observational analysis of patients undergoing open pancreatoduodenectomy through a midline laparotomy. A total of 74 patients were included in the study forming two groups: CWI (n = 33) and TEA (n = 41). TEA resulted in lower median pain scores at rest (p = 0.002) and with coughing (p = 0.005) on postoperative day 2. CWI was non-inferior to TEA for all other pain outcomes measures from days 0-5. Patients in the CWI group had a shorter time to first bowel motion (p = 0.001), commencement of a liquid diet (p = 0.04), earlier removal of nasogastric tube (p = 0.005), abdominal drain (p = 0.003) and indwelling catheter (p < 0.001). Analgesic failure and postoperative nausea and vomiting were also less frequent (p = 0.001 and p < 0.001 respectively). Local CWI with spinal analgesia was non-inferior to TEA for pain management in open pancreaticoduodenectomy. CWI demonstrated advantages in measures associated with enhanced recovery after surgery programs without disadvantages in terms of analgesia requirements.

Abstract 4114716: Concurrent Ethanol Infusion with Pulsed Field Ablation Augments Electroporation of Porcine Atria

Background: Pulsed field ablation (PFA) is a promising modality for treatment of cardiac arrhythmias. PFA increases cell permeability, thereby promoting cell apoptosis. Although greater PFA energy may produce larger lesions, it also carries risks of side effects such as arcing, hemolysis, and microbubbles. Chemical ablation using ethanol (EtOH), such as with injection of the Vein of Marshall, has been used to treat atrial myocardium for refractory atrial arrhythmias. Hypothesis: We hypothesize that PFA in the atria can increase EtOH uptake through PFA-generated pores, thereby augmenting ablation efficacy by utilizing the cell permeability effects of PFA. Aim: The aim of this study is to investigate the effects of local EtOH infusion after PFA on lesion size in porcine atria. Methods: The atria of five porcine subjects were ablated in vivo with low PFA power settings (250V, at 20μs for 50 pulses separated by 200 ms) using a focal bipolar irrigated ablation catheter and BTX 830 electroporation generator (Harvard Apparatus). After PFA, 2 ml of 90 % EtOH vs. saline (control) was infused through the catheter tip to the site of ablation. We compared electrogram voltage amplitude reduction and ablation lesion parameters before and after PFA. Results: A total of 14 control lesions and 14 EtOH lesions were analyzed. There was significant difference in voltage reduction between two groups ( Figure 1A-B ). On gross pathology, there were significant differences in ablation lesion maximum surface diameter, lesion depth, and volume between the 2 lesion sets ( Figure 1C ). Conclusion: Concurrent EtOH infusion after PFA enhanced acute efficacy of electroporation in porcine atria. Adjuvant therapy has the potential to improve efficacy without requiring higher energy parameters, thereby reducing PFA risks. Further studies to assess chronic efficacy are warranted.

The Efficacy of Non-Steroidal Anti-Inflammatory Drugs in Athletes for Injury Management, Training Response, and Athletic Performance: A Systematic Review.

(1) Background: The purpose of this systematic review is to investigate the prevalent use of non-steroidal anti-inflammatory drugs (NSAIDs) in athletes and to comprehensively review the effectiveness and the results of these medications as it relates to injury management, training response, and overall sport performance. (2) Methods: An electronic literature search was performed in accordance with the recommendations and guidelines of the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) protocol. A total of 7 randomized controlled studies met the review's specific inclusion criteria from the 2250 studies initially identified within the PubMed database. (3) Results: In total, 346 adult female and male athletes from a variety of sporting activities and fitness levels were observed, of which 175 athletes were treated with either oral, topical, or local muscular infusion of an NSAID. Depending on study design, the outcomes focused on results obtained through physical exam findings, questionnaires, various performance metrics, and direct tissue sampling from microdialysis or biopsies. Across the 7 total studies, 2 articles focused on injured athletes and their varying pain responses with NSAIDs; 2 studies assessed the limited impact of NSAIDs on performance; and 3 articles revealed the use of NSAIDs correlating to no increases in either collagen synthesis or satellite cell activity after exercise. (4) Conclusions: The systematic review affirmed that NSAIDs can be effective for managing acute pain. However, their value appears to diminish when treating chronic injuries or if NSAIDs are expected to improve performance or have other ergogenic effects in athletes, as the aggregate data did not support such benefits. (5) Practical applications: NSAIDs can be beneficial for athletes in the right situation, but the fact that there are risks and possible disadvantageous results with their use highlights the importance of promoting appropriate expectations and the judicious use of these medications with the athletic community.

Comparing the Effects of Infusion and Bolus Doses of Bupivacaine Applied with Infraclavicular Catheter on the Duration and Need of Postoperative Analgesia

Objective: This study aimed to evaluate postoperative analgesia duration, analgesic requirements, and patient satisfaction between continuous infusion and bolus injection techniques using an infraclavicular catheter in patients undergoing forearm surgery. Material and Method: We examined 100 patients which were divided into 2 groups to evaluate the data retrospectively. Bolus Injection Group (B): Patients who received 4 mL of bupivacaine (0.5%) from the catheter if the VAS value was &gt; 3. Continuous Infusion Group (C): Patients who received 20 mg bupivacaine (0.02%) infusion via catheter using an infusion pump in 24 hours. Demographic data, American Society of Anesthesiologists (ASA) score, intraoperative and postoperative hemodynamic data, sensory and motor block onset times, postoperative Visual Analogue Scale (VAS) (1-2-6-12-24th hour), postoperative 24th and 48th hour satisfaction score, obtained from anesthesia and algology follow-up forms, were evaluated. Results: When both groups were compared, VAS6 and VAS24 values of Group C were found to be statistically significantly lower than Group B. Satisfaction scores revealed that significantly more patients in Group C reported being very satisfied compared to Group B. Conclusion: Our findings suggest that continuous local anesthetic infusion via catheter offers more sustainable analgesia compared to bolus administration.

The Feasibility of Thrombolysis Followed with Ultrasound-Guided Percutaneous Transluminal Balloon Angioplasty in Acutely and Sub-Acutely Thrombosed Arteriovenous Fistulas.

Prompt resolution of arteriovenous fistula (AVF) thrombosis is essential to minimize the need for temporary dialysis catheters. Identifying the ideal timing for the management of thrombosed arteriovenous fistula (AVF) is an area that has not been thoroughly explored. Herein, we examined a local infusion of urokinase for thrombolysis followed by ultrasound-guided percutaneous transluminal balloon angioplasty (PTA) in acute and subacute AVF thromboses. This retrospective cohort research assessed thrombosed AVF in patients referred to the Second Xiangya Hospital. We included patients who underwent local thrombolysis followed by ultrasound-guided PTA treatment between January 1, 2018, and January 1, 2020. Results. We enrolled the records of 86 patients into the present study, including 44 patients with acute AVF thrombosis (group 1: thrombus age, < 72 hours) and 42 patients with subacute AVF thrombosis (group2: thrombus age, 72 hours to seven days). The thrombolytic success rate was 79.5% in group 1 and 42.9% in group 2 (P < .001). All patients underwent ultrasound-guided PTA to dissolve any residual thrombi regardless of thrombolytic success. Technical success after PTA procedures was achieved in 93.2% of patients in group 1 and 88.1% in group 2 (P = .417). Primary patency at six months was comparable between the two groups (67.5% vs. 64.8%, P = .564). We observed that thrombolytic effect does not affect PTA success rate, and six-month patency rate. Direct local infusion of urokinase to the affected area followed by ultrasound-guided PTA constitutes a minimally invasive and effective method for salvaging thrombosed AVF in contrast to abandoning the occluded fistula.

The Excessive Tonic Inhibition of the Peri-infarct Cortex Depresses Low Gamma Rhythm Power During Poststroke Recovery.

The cortex immediately surrounding a brain ischemic lesion, the peri-infarct cortex (PIC), harbors a large part of the potential to recover lost functions. However, our understanding of the neurophysiological conditions in which synaptic plasticity operates remains limited. Here we hypothesized that the chronic imbalance between excitation and inhibition of the PIC prevents the normalization of the gamma rhythm, a waveband of neural oscillations thought to orchestrate action potential trafficking. Probing the local field potential activity of the forelimb primary sensory cortex (S1FL) located in the PIC of male adult mice, we found a constant, deep reduction of low-gamma oscillation power (L-gamma; 30-50 Hz) precisely during the critical time window for recovery (1-3 weeks after stroke). The collapse of L-gamma power negatively correlated with behavioral progress in affected forelimb use. Mapping astrocyte reactivity and GABA-like immunoreactivity in the PIC revealed a parallel high signal, which gradually increased when approaching the lesion. Increasing tonic inhibition with local infusion of GABA or by blocking its recapture reduced L-gamma oscillation power in a magnitude similar to stroke. Conversely, the negative allosteric modulation of tonic GABA conductance using L655,708 or the gliopeptide ODN rescued the L-gamma power of the PIC. Altogether the present data point out that the chronic excess of ambient GABA in the PIC limits the generation of L-gamma oscillations in the repairing cortex and suggests that rehabilitative interventions aimed at normalizing low-gamma power within the critical period of stroke recovery could optimize the restitution of lost functions.

Effect of dexmedetomidine combined with ropivacaine block on flap blood flow and patient satisfaction after flap transfer for hand trauma: a randomized controlled trial.

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Local calcium chloride infusion after pulsed field ablation enhances acute efficacy of cardiac electroporation.

Pulsed field ablation (PFA) has emerged as an innovative therapy for cardiac arrhythmias. Drawing parallels with PFA's application in solid tumors, calcium chloride (CaCl2) as an adjuvant therapy, known as calcium electroporation, may amplify PFA's apoptotic effects. We propose that PFA in the atrium could enhance calcium uptake through PFA-created pores, thereby increasing ablation efficacy even at reduced power levels by exploiting PFA's permeabilization effects. We conducted in vivo ablations on the atria of seven pigs using low PFA power (250 V, 20 μs for 50 pulses at 200 ms intervals). Post-PFA, we randomly administered an infusion of either 200 mg/2 ml CaCl2 (calcium group) or saline (control) directly to the ablation site via the catheter tip. We evaluated reduction in electrogram voltage amplitude, electrocardiography (ECG) parameters, ablation lesion parameters, and histology after PFA. Nineteen lesions from control and calcium groups were examined. Control lesions showed no voltage decrease post-PFA, whereas calcium-treated lesions exhibited a significant voltage reduction. Gross pathology indicated marked differences in maximum lesion surface diameter, depth, and volume between the lesion groups. Histologically, calcium group lesions were characterized by a more severe acute PFA response with contraction band necrosis, myocytolysis and nuclear pyknosis in adjacent myocardium, in addition to microhemorrhages. Infusing calcium chloride locally after PFA markedly improves the immediate efficacy of electroporation in porcine atria. This study suggests that calcium electroporation could bolster PFA outcomes without higher energy levels, potentially diminishing associated risks. These preliminary findings warrant further research into the long-term efficacy and potential clinical application of calcium electroporation in PFA.

Continuous local anaesthetic wound infusion in infants undergoing thoracic or abdominal surgery: A systematic review

ObjectiveTo determine whether continuous local anaesthetic wound infusion (CLAWI) provides more effective pain relief and decrease the need for systemic opioids compared to other analgesic agents in term or preterm newborn infants undergoing thoracic or abdominal surgery. MethodsCochrane Central Register of Controlled Trials, Medline, Embase and CINAHL were searched from database inception to August 2022. Publications were screened and their references were hand-searched to identify additional studies. This review included randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs. Two reviewers independently extracted data and examined the methodological quality of the eligible studies. A meta-analysis was performed for available outcomes. ResultsAfter screening 1202 articles, two RCTs with 98 patients were included. Meta-analysis for combined data was possible for only two outcomes: pain scores post-surgery and length of hospital stay. The random effects model for the pooled standardised mean difference of pain scores between treatment groups post-surgery was -2.54 (95 % CI:7.53, 2.46, p = 0.3196) and for length of stay in the NICU was -0.19 (95 % CI:0.58, 0.21, p = 0.3574), suggesting that CLAWI was not more effective in either providing pain relief or reducing length of stay. However, the small number of studies included, the considerable heterogeneity between the studies, and the small sample sizes of the individual studies limit the generalizability of the findings. ConclusionThis review highlights the need for further, adequately powered well-designed, multicentre trials to examine the effectiveness of CLAWI in reducing postoperative pain in newborns undergoing abdominal and thoracic surgery. Level of evidenceLevel I - Evidence from a systematic review of all relevant randomized controlled trials

Investigation of treatment outcomes for severe extremity trauma in an independent orthopedic trauma center: A case series

BackgroundSevere extremity trauma is one of the most challenging injuries to treat. Limb salvage after severe extremity trauma requires rapid revascularization, accurate and appropriate bone and soft tissue reconstruction, and appropriate management to address critical complications. The purpose of this study was to report the treatment outcomes for severe extremity trauma injuries at our independent orthopedic trauma center. MethodsThis study included patients with severe extremity trauma who underwent major vascular repair or soft tissue reconstruction. Bone reconstruction method, presence or absence of revascularization, and flap type were investigated. Complications were investigated, including revascularization failure, flap failure, infection, and ultimately, whether amputation was required. Additionally, we investigated the number of surgeries performed on each patient at the time of initial hospitalization. ResultsThirty-five patients who underwent revascularization or soft tissue reconstruction were included in this study. Plate fixation was performed in 18 patients, intramedullary nail fixation in 8, screw fixation in 1, pinning in 4, and without implant fixation in 4. Revascularization was performed in six patients, and no vascular complications occurred. Pedicled and free flaps were used in 17 and 16 patients, respectively. Partial flap necrosis occurred in four patients, and arterial occlusion occurred in one. Infection occurred in 10 patients who were treated with frequent irrigation and high-concentration antibiotics local infusion therapy. None of the 35 patients required limb amputation. Mean number of surgeries was 12.5. ConclusionsThe limb of all the 35 patients with severe extremity trauma treated at our independent orthopedic trauma center were salvaged.

Albumin adjuvant therapy for acute ischemic stroke with large vessel occlusion (AMASS-LVO): rationale, design, and protocol for a phase 1, open-label, clinical trial.

Acute ischemic stroke (AIS) is an acute brain injury caused by sudden occlusion of a blood vessel. Endovascular therapy is the most effective way to restore blood flow. However, despite the restoration of blood flow in some patients, their clinical prognosis often remains unsatisfactory. Albumin has shown neuroprotective effects in animal models of AIS. Therefore, this study aims to evaluate the safety, feasibility, and efficacy of local arterial infusions of 20% human serum albumin solution as an adjuvant therapy after endovascular therapy in patients with AIS. This study is a prospective, therapeutic exploratory, non-randomized, open-label, phase 1 clinical trial testing the use of 20% human serum albumin solution injected via the artery immediately after successful reperfusion in patients with AIS. The study is divided into two stages. In the first stage, a single-dose-finding will explore the maximum safe dose according to the 3 + 3 dose escalation principle;, with the maximum dose being 0.60 g/kg. After recanalizing the occluded blood vessel, human serum albumin solution will be injected into the internal carotid artery region through a guiding catheter for 30 min. The second stage involves an albumin adjuvant therapy cohort (AT) and an endovascular treatment lonely cohort (ET). The AT cohort will encompass at least 15 additional participants to complete safety trials at the maximum safe dose determined in the first stage. The ET cohort will include well-matched patients receiving endovascular therapy alone, derived from a contemporaneous prospective registry, who will be excluded from having cardiopulmonary disorders and from receiving any neuroprotective therapy. The primary outcome of this study will be symptomatic intracranial hemorrhage. Efficacy outcomes will include the proportion of patients with the progression of cerebral infarction volume, a modified Rankin Scale of 0-2 on day 90 after randomization. An exploratory secondary outcome will be the analysis of thromboinflammatory and neuroprotective molecule profiles. This pilot trial aims to explore the safety and efficacy of arterial infusion of an albumin solution after occlusive vessel opening in AIS. The results will provide data parameters for subsequent tests on the arterial infusion of albumin solutions. ClinicalTrials.gov, NCT05953623.