The administration of immune checkpoint inhibitors via an elastomeric pump versus conventional intravenous infusion: an economic perspective.

BACKGROUND: Recent studies have underscored the potential of innovative administration methods to mitigate the capacity burden on healthcare systems, without compromising the quality of care. This study assessed and compared the resource utilization and associated costs of two distinct administration modes of immune checkpoint inhibitors: the innovative elastomeric pump and conventional intravenous infusion. This comparison can inform sustainable healthcare practices and healthcare decision-making to optimize treatment efficiency in an era of escalating healthcare demands. METHODS: In this micro-costing study, data on resource use and time allocation for drug preparation and administration were collected using an observational, non-interventional study design. Data were registered at the oncology daycare unit and hospital pharmacy. Cost categories included drug acquisition, disposable materials, healthcare professional time for drug administration, drug preparation, and patient time spent at the oncology day care unit. RESULTS: Drug administration through the elastomeric pump resulted in substantially lower healthcare costs when compared to conventional infusion, particularly due to reduced labor and chair time. The elastomeric pump reduced the total chair time by 78% and nurse time by 55%. Total average costs (excluding drug costs) were €103,47 and €77.99 for conventional infusion and the elastomeric pump, respectively, showcasing potential savings of €25.48 (P < 0.001) per administration. CONCLUSIONS: This study demonstrated that the elastomeric pump not only offers substantial cost savings but also enhances the treatment capacity of the oncology day care unit. These findings support the adoption of the elastomeric pump in clinical settings as a cost-saving and efficient alternative to conventional infusion. TRIAL REGISTRATION: This study has been registered in the National Trial Register (NTR), with the reference number NTR NL9473. Registration date: 05-05-2021.

[Alternatives to the intravenous route in emergency situations]. / Alternatives à la voie intraveineuse en situation d'urgence.

Patients in emergency situations or life distress most often need a intravenous line (IV) to give them the medications they need. The IV route is the preferred route to treat most of the patients in emergency situations out of hospital or in the emergency room but can be very tricky to obtain. Various alternatives have been developed, such as the intraosseous route, particularly useful in cases of venous collapse (shock, cardiorespiratory arrest), the intramuscular route (anaphylaxis, sedation) or the intranasal route (status epilepticus, analgesia). This article reviews the indications, contraindications and pharmacology of these different routes.

Les patients en situation de détresse vitale et d'urgence nécessitent le plus souvent un accès vasculaire veineux, permettant l'administration rapide de thérapeutiques indispensables à la préservation des fonctions vitales. La voie intraveineuse périphérique est l'abord privilégié pour traiter une majorité des patients en situation d'urgence intra ou extrahospitalière, mais elle peut s'avérer complexe à obtenir. Diverses alternatives sont cependant possibles, comme la voie intraosseuse, particulièrement utile en cas de collapsus vasculaire (état de choc, arrêt cardiorespiratoire), la voie intramusculaire (anaphylaxie, sédation) ou encore la voie intranasale (état de mal épileptique, analgésie). Cet article résume les indications, contre-indications et posologies respectives des médicaments susceptibles d'être administrés par ces différentes voies.

VAL-1221 for the treatment of patients with Lafora disease: study protocol for a single-arm, open-label clinical trial.

INTRODUCTION: Lafora disease (LD) is an ultrarare fatal progressive myoclonic epilepsy, causing drug-resistant epilepsy, myoclonus and psychomotor deterioration. LD is caused by mutations in EPM2A or NHLRC1, which lead to the accumulation of polyglucosans in the brain and neurodegeneration. There are no approved treatments for LD. VAL-1221 is a fusion protein comprising the Fab portion of a cell-penetrating antibody and recombinant human acid alpha glucosidase, and has demonstrated an ability to clear polyglucosans. We hypothesise that intravenous infusion of VAL-1221 might be able to degrade cerebral polyglucosans and stabilise or improve disease outcomes. The aim of this study is to assess the safety and preliminary efficacy of VAL-1221 in patients with LD. METHODS AND ANALYSIS: The study is a phase 2, single-arm, open-label, baseline-controlled clinical trial which will be conducted in a single investigational study centre in Italy, namely the sponsor 'IRCCS Istituto delle Scienze Neurologiche di Bologna-Azienda USL di Bologna'. The study will enrol six genetically confirmed patients with mid- to late-stage LD. The global duration of the study for each participant will be 18 months, including screening period, open-label treatment (12 months) and follow-up period. VAL-1221 20 mg/kg will be administered as an intravenous infusion every week for 3 weeks, then every other week. Patients will undergo full clinical assessments at baseline, at an intermediate and at the end-of-treatment visit. The primary objective is to evaluate the safety. The exploratory efficacy endpoints will be related to epilepsy, neuropsychological and motor functions, global assessment and disease burden, in addition to biomarkers. Statistical analyses will be primarily descriptive. ETHICS AND DISSEMINATION: The study protocol was approved by the local ethics committee (number 232-2023-FARM-AUSLBO-23020, 22 March 2023). The results of this study will be disseminated by the investigators through presentations at international scientific conferences and reported in peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: European Union Clinical Trials Register (EudraCT 2023-000185-34).

Effect of intravenous esketamine in emergency cesarean deliveries: a retrospective analysis of maternal and neonatal outcomes.

BACKGROUND: This study investigates the effects of administering intravenous esketamine at a dose of 0.25 mg/kg to pregnant patients receiving epidural anesthesia for emergency cesarean section on both maternal and neonatal outcomes. METHODS: Medical records of pregnant patients transitioning from labor analgesia to epidural anesthesia for emergency cesarean sections between January 2020 and December 2022 were analyzed. The patients were categorized based on whether they received esketamine infusions during the incision-to-delivery interval. The variables compared between the groups included hemodynamic parameters, perioperative and postoperative adverse reactions, and neonatal outcomes (gender, weight, Apgar scores at 1 and 5 min, need for neonatal intensive care, and umbilical artery/vein blood gas analysis). RESULTS: For maternal outcomes, the systolic blood pressure (SBP) in the esketamine group showed a significant increase at 5 and 10 min' post-administration, and the diastolic blood pressure (DBP) significantly increased at 5 min, compared to the control group (p < 0.01). No significant differences were observed in heart rate (HR) and oxygen saturation (SpO2) at any time point (p > 0.05). The esketamine group experienced a significant rise in the incidence of arrhythmias, dizziness, and nystagmus during the perioperative period, a notable decrease in hypotension incidence, and an increase in postoperative nausea and dizziness. Regarding neonatal outcomes, there were no significant differences in gender, weight, Apgar scores ≤7 at 1 and 5 min, and the need for neonatal intensive care. However, the pH level in the umbilical artery blood of the esketamine group was significantly higher. The levels of PCO2 and PO2 in umbilical artery and venous blood did not show significant differences between the groups. CONCLUSIONS: In pregnant women undergoing emergency cesarean section, intravenous administration of 0.25 mg/kg esketamine is correlated with favorable maternal and neonatal outcomes.

A Pressure-Based Model of IV Fluid Therapy Kinetics.

The kinetics of intravenous (IV) fluid therapy and how it affects the movement of fluids within humans and animals is an ongoing research topic. Clinical researchers have in the past used a mathematical model adopted from pharmacokinetics that attempts to mimic these kinetics. This linear model is based on the ideas that the body tries to maintain fluid levels in various compartments at some baseline targets and that fluid movement between compartments is driven by differences between the actual volumes and the targets. Here a nonlinear pressure-based model is introduced, where the driving force of fluid movement out of the blood stream is the pressure differences, both hydrostatic and oncotic, between the capillaries and the interstitial space. This model is, like the linear model, a coarse representation of fluid movement on the whole body scale, but, unlike the linear model, it is based on some of the body's biophysical processes. The abilities of both models to fit data from experiments on both awake and anesthetized cats was analyzed. The pressure-based model fit the data better than the linear model in all but one case, and was deemed statistically significantly better in a third of the cases.

Sanhuang ointment prolongs indwelling time and promotes vein injury repair in patients receiving intravenous infusion via peripheral venous indwelling needles.

We investigated the effect of Sanhuang ointment on the indwelling time and vein injury repair in patients receiving intravenous infusion via peripheral venous indwelling needles. Patients (n=120) who received infusion via peripheral venous indwelling needles were randomized into Sanhuang ointment, Hirudoid and blank control groups. The indwelling time, venous injury and repair rate, venous intimal roughness rate, vascular wall thickening rate, thrombosis rate and blood flow velocity were compared within 24h and on day 4 post-needle removal. The indwelling time in the Sanhuang ointment group was 7 (6,8) days, significantly longer than that in the Hirudoid (5(4,6) days) and blank control groups (4(3,5) days) (P<0.01). Within 24h of needle removal, differences in venous injury and repair grades, intimal roughness, wall thickening, thrombosis and blood flow were not significant (P>0.05). On day 4, the rates of venous intimal roughness, vascular wall thickening and thrombosis were significantly lower, while the blood flow velocity and venous repair rates were significantly higher in the Sanhuang ointment group than those in the Hirudoid and blank control groups (P<0.05). Sanhuang ointment application extends peripheral venous indwelling time and promotes vein repair without increased injury risk.

No benefit from the addition of low-dose ketamine infusion to standard evidence-based care of patients with multiple rib fractures.

BACKGROUND: Multiple rib fractures from blunt thoracic trauma cause significant morbidity. Optimal current management includes multimodal analgesia, pulmonary hygiene, and early mobilization. Low-dose ketamine infusion (LDKI) has been proposed as an adjunctive analgesic in this setting. A prior study reported decreased pain scores with LDKI in patients with multiple rib fractures. We hypothesized that LDKI would decrease morphine milligram equivalents (MMEs) in patients with multiple rib fractures. METHODS: A prospective randomized placebo-controlled trial was performed in adult (18 years or older) patients with three or more rib fractures. A prestudy power analysis calculated an 80% chance of identifying a 15% decrease in MMEs with 50 subjects. The study was approved by the institutional review board and informed consent obtained in all subjects. Demographic (age, sex) and injury specific information (Injury Severity Score, number of rib fractures) were obtained. Subjects were randomized 1:1 to receive continuous LDKI (0.1 mg/kg/h) or placebo infusion (0.9% NaCl) for ≤48 hours. All patients received a standard evidence-based multidisciplinary protocol for rib fractures management. Primary outcome measure was MME use or pulmonary complications. Statistical comparison of LDKI versus placebo was performed using the Mann-Whitney U test. RESULTS: All 50 enrolled subjects (placebo, 25; LDKI, 25) received study drug infusion. The two groups were well matched for age, Injury Severity Score, and number of rib fractures. We observed no differences in the Day 1 (p = 0.961), Day 2 (p = 0.373), or total MMEs (p = 0.946) between groups. Similar total MME use was observed when subjects who received ≥40 hours of study drug and were compared (p = 0.924). Use of LDKI did not alter subsequent need for opiate analgesics postinfusion, hospital length of stay, pulmonary complications, or need for readmission. CONCLUSION: The addition of LDKI to an established multimodal, evidence-based protocol for management of multiple rib fractures did not decrease opiate usage or impact pulmonary complications. LEVEL OF EVIDENCE: Therapeutic/Care Managaement; Level I.

Peripheral intravenous therapy infiltration and extravasation (PIVIE) risks in 11 006 paediatric surgery inpatients in China: a retrospective observational study.

OBJECTIVE: To determine the risk factors associated with peripheral intravenous therapy infiltration and extravasation (PIVIE) in paediatric surgery inpatients. METHODS: This retrospective observational study was conducted at a tertiary general hospital in Sichuan, China. Logistic regression was employed to identify independent risk factors predictive of PIVIE. Kaplan-Meier survival analysis was undertaken to determine the relationship between the occurrence of PIVIE and the duration of that event (survival time). RESULTS: This study included 11 006 paediatric surgery inpatients and 19 771 peripheral intravenous catheters (PIVCs). The incidence of PIVIE was 16.93% (3347 of 19 771). The following were significant predictors of PIVIE: sex (odds ratio [OR] 0.834; 95% confidence interval [CI] 0.772, 0.900); age (OR 0.945; 95% CI, 0.934, 0.956); disease classification (OR 0.962, 95% CI 0.950, 0.976); puncture site (OR 1.061; 95% CI 1.044, 1.078); and indwelling time (OR 1.257; 95% CI 1.215, 1.300). CONCLUSIONS: Sex, age, type of disease, puncture site and indwelling time were risk factors for PIVIE. The puncture site should be effectively assessed and accurately selected. Informed judgements should be based on the child's sex, age and medical condition, so that the appropriate preventive measures to minimize the risk of PIVIE can be implemented.

Medical Costs and Caregiver Burden of Delivering Disease-Modifying Alzheimer's Treatments with Different Duration and Route of Administration.

BACKGROUND: Multiple disease modifying treatment for Alzheimer's disease are currently in clinical development or have been recently approved for use. They have vastly different treatment properties but so far, little work has been done to quantify the impact of treatment properties on the treatment's value in terms of medical and social care costs and caregiver burden. OBJECTIVES: This study aims to analyze how the mode of treatment administration, treatment frequency and duration, and monitoring requirements affect the value of disease modifying treatments. In order to isolate these effects, we compare five hypothetical disease modifying treatments with equal efficacy and safety: (1) chronic bi-weekly intravenous infusion, (2) chronic four-weekly intravenous infusion, (3) 52 weeks fixed duration four-weekly intravenous infusion, (4) chronic subcutaneous injections, and (5) chronic oral prescription on their direct medical costs, caregiver burden, and preservation of treatment value. DESIGN: Survey of Alzheimer's disease treatment clinics and retrospective data analysis. SETTING: United States. MEASUREMENTS: Direct medical cost and caregiver burden of treatment administration and monitoring compared to gross treatment benefit. RESULTS: Chronic bi-weekly infusion treatment had the highest direct medical cost ($45,208) and caregiver burden ($6,095), reducing the treatment value by 44%, while oral treatment with the lowest direct medical cost ($1,983) and caregiver burden ($457) reduced the treatment value by only 2%. Substantial caregiver burden was reported from the survey, with a reported average of 2.3 hours for an office visit and infusion, 44 minutes of round-trip travel time, and 78% of patients being accompanied by a caregiver for treatment. CONCLUSION: Burden of chronic intravenous treatments exceed the gross medical and social care cost savings and value of caregiver benefit. The results suggest the need for less complex treatments that require fewer clinic visits to preserve the economic value of disease modifying treatments.

A multicenter retrospective study on comparing the efficacy and safety of the therapy of intermittent cyclophosphamide and corticosteroids versus rituximab for primary membranous nephropathy.

BACKGROUND: Few clinical studies compare the long-term remission, relapse, and safety of rituximab (RTX) or a combination of intermittent intravenous infusion of cyclophosphamide (CTX) and oral corticosteroid for primary membranous nephropathy (PMN) patients. METHODS: We collected multicenter retrospective data on PMN patients with nephrotic syndrome who received RTX or intermittent intravenous CTX with oral corticosteroids between 1 January 2019 and 31 January 2024. Patients were followed up until two years after receiving immunotherapy. The primary outcomes were a composite of complete or partial remission rates at 6, 12, and 24 months. The secondary outcomes were the relapse and safety evaluation. RESULTS: Forty patients treated with RTX and 27 with the CTX regime were available for analysis. No significant difference in the remission rate at 6, 12, or 24 months was observed between the two groups (p > .05). Kaplan-Meier's survival analysis showed that the relapse-free cumulative survival rate of the RTX group was superior to that of the CTX group (p = .023). Compared with baseline, both the media of urine protein and serum albumin levels in the two groups showed a significant improvement at 6 months and maintained through to the second year. No significant difference in the occurrence of total side effects between the two groups (p = .160). CONCLUSIONS: There was no difference in remission rates and safety between RTX versus intermittent intravenous CTX combined with oral corticosteroid treatment for patients with PMN within 2 years. RTX appeared to have benefits in terms of prolonging relapse-free survival.

Morphological correlates of anxiety-related experiences during a ketamine infusion.

OBJECTIVES: Ketamine exerts rapid antidepressant effects by enhancing neuroplasticity, particularly in the amygdala and hippocampus-regions involved in fear processing and learning. While the role of ketamine's dissociative effects in its antidepressant response is debated, anxiety experienced during infusion has been negatively correlated with treatment outcomes. METHODS: In this single-blind, placebo-controlled study, a subset of 17 healthy volunteers (6 males, 23.12 ± 1.9 years) received intravenously a placebo in the first and 0.5 mg/kg racemic ketamine in the second session. Anxiety-related experiences were assessed by the 5D-ASC score obtained post-infusion, structural magnetic resonance imaging scans were acquired 4 h post-infusion. An anxiety-score was obtained from the 5D-ASC. Relation between post-placebo amygdala volume, hippocampal volume, and its subfields with the anxiety-score were assessed using linear regression models. RESULTS: Results showed a statistically significant negative relation between hippocampal head volume and the anxiety score (ß = -0.733, p = 0.006), with trending negative association for each subfield's head and the score. CONCLUSION: These findings suggest that anxiety-related experiences during ketamine infusion may be mediated by the hippocampus, with smaller hippocampal volumes leading to more anxiety-related experiences. Thus, hippocampal subfield volumes may be used as a predictor for anxiety-related events during ketamine use and might predict treatment outcome in future approaches.

Bone marrow mesenchymal stem cell-derived extracellular vesicle infusion for amyotrophic lateral sclerosis.

Background: In this pilot safety study, we hypothesized that a human bone marrow stem cell-derived extracellular vesicle (hBM-MSC EV) investigational product (IP) would be safe and exhibit potential efficacy in amyotrophic lateral sclerosis (ALS) patients.Methods: Ten ALS patients received two 10-ml intravenous infusions of the IP given 1 month apart and evaluated over 3 months.Results: There were no serious adverse events or adverse events related to the IP and 30% of subjects' ALS functional rating scale-revised (ALSFRS-R) scores did not decline.Conclusion: HBM-MSC EVs appear safe in ALS patients. This early investigation suggests a controlled study of EVs for the treatment of ALS is warranted.

Amyotrophic lateral sclerosis (ALS) is a nervous system disease that affects the brain and spinal cord, causing the loss of muscle control. Currently, there is no cure for ALS and the disease gets worse over time. A potential new treatment is being investigated using mesenchymal stem cell extracellular vesicles (MSC EVs). MSC EVs are small structures that contain useful molecules and proteins that can be transported to cells affected by the disease, helping to reduce inflammation and encouraging repair. This 3-month study looked at the safety of human bone marrow MSC-EVs (hBM-MSC EVs) given as treatment to ten ALS patients, as well as how well it worked at delaying worsening of the disease. They found that there were no serious side effects caused by the treatment and that hBM-MSC EVs may have the potential for delaying the progression of ALS. This indicates that more, larger studies need to be carried out to find out treatment specifics, such as dose (how much of the treatment to give) and frequency (how often to give the treatment), and how they could be related to patient outcomes.

A dose-adjusted, open-label, pilot study of the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis.

Increased circulating histones correlate with sepsis severity and are a potential therapeutic target. Pre-clinical studies showed benefit with a histone-neutralizing polyanion molecule (STC3141). We aimed to investigate the safety, tolerability, and pharmacokinetics of STC3141 in critically ill patients with sepsis. We studied 26 patients with sepsis divided into four cohorts of one, five, ten, and ten subjects, respectively. We conducted a dose-adjusted, open-label study to determine the safety, tolerability, and pharmacokinetics of STC3141 administered as an IV infusion for up to 72 h, with rate adjusted to estimated creatinine clearance. Four steady-state concentrations were targeted. Twenty of the 26 subjects (77%) in the study experienced at least one adverse event (AE). The most frequently reported study drug-related AE was a mildly prolonged aPTT (four events). Only one AE (pulmonary hemorrhage) led to discontinuation of the drug. After excluding patients receiving renal replacement therapy (RRT) patients, clearance ranged from 3.3 to 4.2 L/h across cohorts and was essentially completely renal in nature. Half-life values ranged from 5 to 7 h. The mean (±SD) terminal half-life for non-RRT subjects and for whom it was possible to calculate was approximately 9 (±4.77) h but increased to 19 (±7.94) h for subjects on RRT. Overall, 18 (69.2%) patients completed the study to day eight in the ICU, and 22 (84.6%) survived to 28 days. STC3141 administration appeared to have an acceptable degree of safety and tolerability and expected pharmacokinetics. Cautious, larger randomized efficacy trials in sepsis appear justified.

Real-world efficacy and safety of intravenous ferric carboxymaltose for the management of iron deficiency anaemia in Malaysia: A single centre cohort study.

INTRODUCTION: Up to 24.2% Malaysians are estimated to be affected by anaemia. Iron deficiency is the most common nutritional deficiency leading to anaemia. Oral iron therapy may not be well tolerated or efficient. Ferric carboxymaltose (FCM), a non-dextran intravenous iron formulation, may be an appealing alternative for iron replacement therapy. This retrospective study aimed to investigate the efficacy and safety of intravenous FCM infusion for the management of iron deficiency anaemia in a single centre in Malaysia. MATERIALS AND METHODS: All patients who received at least one dose of 500 mg intravenous FCM infusion from January to December 2023 in Bukit Tinggi Medical Centre (BTMC) were identified from the electronic medical record database. Inclusion criteria were patients: (1) ≥ 14 years old and (2) with iron deficiency anaemia. The primary outcome was the mean change in haemoglobin level before treatment and 30 day after treatment. Secondary outcomes included reasons for intravenous FCM infusion, median dose, adverse drug reactions, mean change in haemoglobin levels for different subgroups and percentage of patients with normalised haemoglobin after treatment. The efficacy outcome was analysed using per-protocol analysis while the safety outcome used intention-to-treat analysis. Paired t-test was used to compare the mean difference between the haemoglobin measurements before and 30-day after treatment. RESULTS: A total of 144 administrations were given to 141 patients requiring intravenous iron replacement therapy during the 1-year study period in BTMC. Intravenous FCM infusion was administered for the management of iron deficiency related to: (1) increased blood loss, including menorrhagia, haemorrhoids and GI-related surgery, (2) low iron intake, including poor nutrition and gastrointestinalrelated malabsorption and (3) haematological disorders, including autoimmune haemolytic anaemia, myelodysplastic syndrome, diffuse large B-cell lymphoma and idiopathic thrombocytopaenia purpura. The median dose of intravenous FCM infusion was 1000 mg. At 30 day post-infusion, the mean haemoglobin level increased significantly from 8.9 g/L to 11.6 g/L (p < 0.05), an increase of 2.68 g/L (95% CI: 2.45 - 2.90 g/L). No adverse drug reactions were reported. Subgroup analysis showed that patients with haematological disorders had significantly higher improvement in haemoglobin levels after intravenous iron infusion compared to those without. At 7-day, 14-day, 21-day post-infusion, 33% (33/99), 34% (34/99) and 36% (36/99) patients had a normalised haemoglobin level, respectively. The proportion of patients with a normalised haemoglobin level increased to 36% (36/99) and 42% (42/99) at 30-day and 90-day post-infusion. CONCLUSION: Within the limit of this single-centre retrospective study, intravenous FCM infusion was well tolerated and effective in increasing the haemoglobin level among patients with iron deficiency anaemia.

Clinical Experience with Simultaneous Mixed Infusion of Trastuzumab and Pertuzumab in the Neo-Peaks Study (JBCRG-20 Sub-Study).

Dual human epidermal growth factor receptor 2(HER2)blockade with trastuzumab(H)and pertuzumab(P)combined with docetaxel and carboplatin(TCb)is a standard neoadjuvant therapy for HER2-positive breast cancer patients. We conducted this sub-study using data from the investigator-initiated randomized phase 2 JBCRG-20(Neo-peaks)study to evaluate the safety of simultaneous mixed HP infusion in Japanese patients, as there have been no data to date. A total of 204 patients in groups A-C received TCbHP, TCbHP followed by trastuzumab emtansine(T-DM1)+P, and T-DM1+P, respectively. Of the 103 patients in groups A and B who received H and P by sequential infusion in cycle 1, the 17(median age 59; range 29-69 years)who did not experience an infusion reaction(IF)received these agents as a mixed, single-bag infusion from cycle 2 onwards. No cases of IF were observed, thus 71 mixed doses were safely administered. Administration time was reduced to 60 min from cycle 3 onwards. Furthermore, in the group B patients, mixed HP infusion did not affect their subsequent treatment(i. e. 4 cycles of T-DM1+P). Simultaneous administration of H and P enables a reduced administration time, which would benefit both patients and healthcare providers.

[Observation of the effect of single dose intravenous infusion of tranexamic acid on white blood cell, erythrocyte sedimentation rate and C-reactive protein after double segmental posterior lumbar interbody fusion].

OBJECTIVE: To observe the safety and effectiveness of single dose intravenous infusion of tranexamic acid (TXA) in dual level posterior lumbar interbody fusion (PLIF), and to explore the changes and trends in perioperative white blood cell (WBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). METHODS: Between October 2020 and September 2022, 46 patients with lumbar degenerative disease were treated with dual level PLIF, including 18 males and 28 females, with an average age of (60.24±10.68) years old, from 34 to 80 years old. They were divided into observation group and control group according to different treatment methods. There were 28 patients in the observation group, including 12 males and 16 females, with an average age of (61.04 ± 9.03) years old. There were 3 cases with lumbar disc herniation (LDH), lumbar spinal stenosis (LSS) 18 cases, lumbar spondylolisthesis (LS) 7 cases. TXA (1 g/100 ml) was administered intravenously 15 min before skin incision after general anesthesia. The control group consisted of 18 patients, including 6 males and 12 females, with an average age of (59.00±13.04) years old. There were 5 cases with LDH, LSS 9 cases, LS 4 cases, and TXA was not used. The operation time, intraoperative bleeding volume, postoperative drainage volume, postoperative deep vein thrombosis (DVT), postoperative hospital stay, postoperative activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT), fibrinogen (FIB), platelet (PLT), red blood cell (RBC), hemoglobin (HB), hematocrit (HCT), the first day, the fourth day, the seventh day and the last tested after operation WBC, ESR and CRP were recorded. RESULTS: The postoperative wounds of the patients healed well and there was no DVT. 46 patients were followed up from 3 to 6 months. The intraoperative blood loss was 400.0 (300.0, 500.0) ml and the postoperative drainage was 260.0 (220.0, 450.0) ml in the observation group, which were lower than the control group[600.0(400.0, 1000.0) ml, 395.0 (300.0, 450.0) ml], P<0.05. There was no significant difference between the two groups in operation time, postoperative hospital stay, postoperative APTT, PT, TT, FIB, PLT, RBC, HB, HCT, and postoperative WBC, ESR and CRP at different times (P>0.05). CONCLUSION: Single dose intravenous infusion of TXA can reduce the blood loss of bi-segmental PLIF, and has no significant effect on WBC, ESR and CRP after operation.

Comparison of the Effectiveness of Warmed Versus Room Temperature Intravenous Fluids Administration to Prevent Intraoperative Heat Loss in Anaesthetised Calves Undergoing Umbilical Herniorrhaphy.

BACKGROUND: Warmed intravenous (IV) fluids administration to prevent hypothermia provide controversial results in humans, cats and dogs, but its effect on calves is unknown. OBJECTIVXE: To evaluate the effectiveness of warmed IV fluids administered to prevent intraoperative heat loss in anaesthetised calves undergoing umbilical herniorrhaphy. METHODS: Thirty Simmental breed calves (aged 10-30 days) were randomly divided between two equal groups, wherein the infusion fluid (Ringer's lactate, 5 mL/kg/h) was administered either at room temperature (Group RoT) or warmed (Group WF). Pulse rate (PR), respiratory rate (fR), peripheral haemoglobin oxygen saturation (SpO2) and rectal temperature (RT) were recorded immediately after the onset of anaesthesia induction (T0) at T5, T10, T15, T30, T45 and T60. Duration of anaesthesia, surgery time and recovery scores were also noted. RESULTS: The PR, RT and fR values showed no significant difference between groups over time (p > 0.05). There was no significant difference in duration of anaesthesia, surgery time or recovery score between groups (p > 0.05). CONCLUSIONS: The findings of the current study suggest that warmed IV fluid as the warming method did not prevent intraoperative hypothermia in calves. A constant-rate infusion of warmed fluid (5 mL/kg/h) is insufficient to prevent intraoperative hypothermia in calves.

Low-dose dobutamine in acute myocardial infarction with intermediate to high risk of cardiogenic shock development (the DOBERMANN-D trial): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial.

BACKGROUND: Cardiogenic shock (CS) occurs in 5-10% of patients with acute myocardial infarction (AMI), and the condition is associated with a 30-day mortality rate of up to 50%. Most of the AMI patients are in SCAI SHOCK stage B upon hospital arrival, but some of these patients will progression through the stages to overt shock (SCAI C-E). Around one third of patients who develop CS are not in shock at the time of hospital admission. Pro-B-type natriuretic peptide (proband) is a biomarker closely related to CS development. The aim of this study is to investigate the potential for preventing progression of hemodynamic instability by early inotropic support with low-dose dobutamine infusion administrated after revascularization in AMI patients with intermediate to high risk of in-hospital CS development. METHODS: This investigator-initiated, double-blinded, placebo-controlled, randomized, single-center, clinical trial will include 100 AMI patients (≥ 18 years) without CS at hospital admission and at intermediate-high risk of in-hospital CS development (ORBI risk score ≥ 10). Patients will be randomized in a 1:1 ratio to a 24 h intravenous (IV) infusion of dobutamine (5 µg/kg/min) or placebo (NaCl) administrated after acute percutaneous coronary intervention (PCI) (< 24 h from symptom onset). Blood samples are drawn at time points from study inclusion (before infusion, 12, 24, 36, and 48 h). The primary outcome is peak plasma proBNP within 48 h after infusion as a surrogate-measure for the hemodynamic status. Hemodynamic function will be assessed pulse rate, blood pressure, and lactate within 48 h after infusion and by transthoracic echocardiography (TTE) performed after 24-48 h and at follow-up after 3 months. Markers of cardiac injury (troponin T and creatine kinase MB (CK-MB)) will be assessed. DISCUSSION: Early inotropic support with low-dose dobutamine infusion in patients with AMI, treated with acute PCI, and at intermediate-high risk of in-hospital CS may serve as an intervention promoting hemodynamic stability and facilitating patient recovery. The effect will be assessed using proBNP as a surrogate marker of CS development, hemodynamic measurements, and TTE within the initial 48 h and repeated at a 3-month follow-up. TRIAL REGISTRATION: The Regional Ethics Committee : H-21045751. EudraCT: 2021-002028-19. CLINICALTRIALS: gov: NCT05350592, Registration date: 2022-03-08. WHO Universal Trial Number: U1111-1277-8523.