Clinical Effectiveness and Safety of Transarterial Chemoembolization: Hepatic Artery Infusion Chemotherapy Plus Tyrosine Kinase Inhibitors With or Without Programmed Cell Death Protein-1 Inhibitors for Unresectable Hepatocellular Carcinoma-A Retrospective Study.

BACKGROUND: Locoregional treatment with transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC) and systemic targeted immunotherapy with tyrosine kinase inhibitors (TKI) and programmed cell death protein-1 (PD-1) inhibitors in the treatment of unresectable hepatocellular carcinoma (uHCC) have achieved promising efficacy. The retrospective study aimed to evaluate the efficacy and safety of TACE and HAIC plus TKI with or without PD-1 for uHCC. PATIENTS AND METHODS: From November 2020 to February 2024, the data of 44 patients who received TACE-HAIC + TKI + PD-1 (THKP group) and 34 patients who received TACE-HAIC + TKI (THK group) were retrospectively analyzed. Primary outcomes were overall survival (OS) and progress-free survival (PFS), and secondary outcomes were objective response rate (ORR), disease control rate (DCR), conversion rates, and adverse events (AEs). RESULTS: A total of 78 patients were recruited in our single-center study. The patients in THKP group had prolonged median OS [25 months, 95% confidence interval (CI) 24.0-26.0 vs 18 months, 95% CI 16.1-19.9; p = 0.000278], median PFS [16 months, 95% CI 14.1-17.9 vs 12 months 95% CI 9.6-14.4; p = 0.004] and higher ORR (38.6% vs 23.5%, p = 0. 156) and DCR (88.6% vs 64.7%, p = 0.011) compared with those in THK group. Multivariate analysis showed that treatment option and alpha-fetoprotein (AFP) level were independent prognostic factors of OS and PFS. The frequency of AEs were similar between the two groups. CONCLUSIONS: The THKP group had better efficacy for uHCC than the THK group, with acceptable safety.

Comparison of the effects of single injection and continuous infusion popliteal nerve block on pain and hemodynamics in diabetic foot surgery; prospective randomized clinical trial.

Objectives: In patients undergoing surgery due to diabetic foot complications from uncontrolled diabetes may lead to neuraxial or general anesthesia-related issues. Regional anesthesia techniques can be preferred to prevent these complications. This study aimed to compare the hemodynamic effects and outcomes in terms of pain of continuous infusion and single injection methods of popliteal nerve block in patients undergoing surgery due to diabetic foot. Materials and methods: Sixty-three patients in ASA II-IV risk group scheduled for diabetic foot surgery were randomized into two groups for popliteal nerve block as the anesthesia method. Group 1 (n:32), 30 mL of local anesthetic was administered around the popliteal nerve under ultrasound guidance and nerve stimulator. Group 2 (n:31) had a catheter placed beyond the needle tip by 4-5 cm. An elastomeric pump was prepared for the infusion of 2 mL/h of 0.25 % bupivacaine through the catheter. Hemodynamic parameters before and after the block, onset, block duration times, postoperative pain scores, time to analgesic requirement, patient satisfaction, and discharge time were recorded. Results: Pain scores were higher in Group 1 after 12 h postoperatively and in Group 2 after 60 h postoperatively (p = 0.006, p < 0.01, respectively). The time to the first analgesic requirement was not statistically different between Group 1 (mean 804.64 ± 1020.8 min) and Group 2 (mean 2012.78 ± 1424 min) (p = 0.072). There was no significant difference in systolic, diastolic, mean arterial blood pressure, and heart rate between groups before and after successful blockade (p > 0.05). Conclusions: Continuous infusion method of popliteal nerve block provides a longer pain-free period. Both methods showed similar hemodynamic data and low pain scores. Although continuous infusion method provides better analgesia, its procedural cost, technical difficulties, and adverse effects on patient comfort should also be considered.

A Skin Testing Strategy for Non-IgE-mediated Reactions Associated with Vancomycin.

BACKGROUND: Vancomycin infusion reaction (VIR), reportedly mediated through Mas-Related G Protein-Coupled Receptor-X2 (MRGPRX2), is the primary vancomycin-induced immediate drug reaction (IDR). Clinically, distinguishing the underlying drug-induced IDR mechanisms is crucial for future treatment strategies, including drug restriction, re-administration, and pretreatment considerations. However, the lack of validated diagnostic tests makes this challenging, often leading to unnecessary drug restriction. OBJECTIVE: To determine if intradermal tests (IDTs) and, separately, the basophil activation test (BAT) differentiate VIR from vancomycin-tolerant subjects. METHODS: Cross-sectional study of vancomycin-exposed adults with and without a history of VIR. Demographics, allergy-related comorbidities, history of vancomycin exposures, and VIR characteristics were collected. IDT with vancomycin was performed. IDT dose responses EC50, IDT-related local symptoms, and BAT were compared between groups. RESULTS: 11 VIR and 10 vancomycin-tolerant subjects were enrolled. The most reported VIR symptoms were pruritus (82%), flushing (82%), hives (46%), hives (46%), angioedema (27%), and dyspnea (19%). The IDT dose response mean EC50 was 328 µg/mL (95% CI 296, 367) in the VIR vs. 1,166 µg/mL (95% CI 1029, 1379) in the tolerant group (p<0.0001). All VIR subjects reported IDT-related local pruritus compared to 60% of tolerant subjects (p=0.0185). The %CD63+ basophils were consistently <2%, without significant differences between groups (p < 0.54). CONCLUSIONS: Variations in skin test methodologies could help identify other IDR mechanisms beyond IgE. This skin test protocol holds the potential for identifying VIR, particularly in cases where patients have received multiple drugs while BAT is insufficient. Future studies will validate and delineate its predictive value, assessing the risk of VIR.

Patients with type 2 diabetes who achieve reduced postprandial glucose levels during insulin intensive therapy may have a better recovery of ß-cell function.

OBJECTIVES: To explore parameters that may determine the improvement in C-peptide levels in patients with type 2 diabetes (T2D) receiving continuous subcutaneous insulin infusion (CSII) therapy. METHODS: The trial included a lead-in period for collecting baseline parameters and correcting hyperglycemia, a 4-day CGM period, and a 2-3 weeks treatment period. After screening, patients were hospitalized and randomized to the metformin add-on NovoRapid group or the Prandilin group. Once the glycemic target was reached, all patients underwent a 4-day CGM, with treatments maintained for 2-3 weeks. OGTTs were performed at baseline and endpoint. The primary endpoint was identifying factors contributing to better ß-cell function recovery after CSII therapy. RESULTS: A total of 99 recruited patients were admitted as inpatients and achieved glycemic control within 3.8 ± 1.1 days. Of these, 83 (84 %) patients showed improvement in C-peptide levels, while 16 (16 %) did not show any change in C-peptide levels at the endpoint. Pearson analysis showed a negative correlation between the incremental AUC of glucose concentration (from 0700 to 1000) and the increase in incremental AUC of C-peptide levels (r = -0.199, P < 0.05). CONCLUSIONS: Drug-naïve T2D patients with lower postprandial glucose concentration during CSII therapy exhibit better ß-cell function recovery.

A case of anaphylactic shock to human fibrinogen infusion during cardiac surgery.

Human fibrinogen (FIB) has been clinically proven to be considerably effective for the treatment of postoperative bleeding, with reported cases of allergic reactions to human FIB being rare. Here, we report a case of an anaphylactic shock in 27-year-old patients with rheumatic heart valve disease who received a human FIB infusion during mitral valve replacement, aortic valve replacement, and tricuspid valve-shaping surgery. The patients showed generalised profuse sweating, a barely noticeable skin rash, faint pulse, systolic pressure < 50 mmHg, and a heart rate of 71 beats/min. We share insights from a case of severe allergy to human FIB infusion during cardiac surgery, through which we have gained experience in the processes of diagnosing and treating. This report aims to provide a preliminary summary of the characteristics of this case to serve as a reference for fellow clinicians.

Combination Therapy of Lenvatinib and Hepatic Arterial Infusion Chemotherapy Using Cisplatin With Lipiodol and 5-Fluorouracil: A Potential Breakthrough Therapy for Unresectable Advanced Hepatocellular Carcinoma.

INTRODUCTION: In 2021, the LEOPARD trial reported that the combination of lenvatinib+one-shot cisplatin infusion might contribute to improving the results of conventional advanced hepatocellular carcinoma (HCC) treatment. Thus, combination therapy with lenvatinib and catheterization has emerged as a focal point in treating advanced HCC. Conversely, the New FP regimen consists of low-dose cisplatin (CDDP) combined with 5-fluorouracil (5-FU) and lipiodol via hepatic arterial infusion chemotherapy (HAIC), with a high response rate of approximately 70%. Therefore, lenvatinib+New FP (LEN-New FP) may be a more promising treatment for HCC. Here, we report six patients who were administered LEN+New FP and achieved high therapeutic efficacy. Among them, one case had an interesting clinical course, which has been described in detail. MATERIALS AND METHODS: This study included six patients who were administered 12 mg or 8 mg of lenvatinib once daily based on a body weight of ≥60 kg or <60 kg, respectively, along with 50 mg of cisplatin in 5-10 mL lipiodol, and a continuous infusion of 5-FU (1500 mg/5 days) infused every 2-4 weeks. Tumor evaluations were performed 4-8 weeks after the initiation of New FP administration and every 8-12 weeks thereafter. RESULTS: The median patient age was 65 years. All patients had a history of prior treatment with atezolizumab and bevacizumab and one of the factors associated with poor overall survival for New FP monotherapy, such as a maximum tumor diameter ≥7 cm and bilobular multifocal distribution. Four (67%) patients had severe vascular invasion. The best objective response and disease control rates were 83% and 100%, respectively. The best response of the target lesion was complete remission in four out of six patients. CONCLUSION: The LEN-New FP combination for advanced HCC showed a high response rate and was more effective in high-risk patients with factors associated with poor overall survival than that reported with conventional New FP monotherapy. Additionally, LEN-New FP exhibited extremely high objective response and disease control rates and was well tolerated, including in cases where it was considered second- or third-line systemic chemotherapy for advanced HCC. Thus, LEN-New FP can serve as a breakthrough therapy for advanced HCC based on appropriate case selection.

[Clinical observation on acupuncture at infusion points of "four seas" on refractory peripheral facial paralysis].

OBJECTIVE: To observe the clinical effect of acupuncture at the infusion points of "four seas" for refractory peripheral facial paralysis on the basis of conventional acupuncture. METHODS: A total of 52 patients with refractory peripheral facial paralysis were randomized into an observation group (26 cases, 2 cases dropped out) and a control group (26 cases, 1 case dropped out). On the basis of conventional acupuncture (Yintang [GV 24+] and Yangbai [GB 14], Dicang [ST 4] at affected side, etc.), acupuncture at the infusion points of "four seas", i.e. Baihui (GV 20), Dazhui (GV 14) and bilateral Shangjuxu (ST 37), Xiajuxu (ST 39), Zusanli (ST 36), was delivered in the observation group. On the basis of conventional acupuncture, shallow acupuncture was applied at corresponding non-meridian and non-acupoint points of the infusion points of "four seas" in the control group. The needles were maintained for 30 min, the treatment was given once every other day, 3 times a week for 4 weeks in the two groups. Before and after treatment, the House-Brackmann (H-B) facial nerve grading and the dynamic view score of the facial nerve function scoring system were observed, and the clinical efficacy was evaluated after treatment in the two groups. RESULTS: After treatment, the H-B facial nerve grading was improved compared with that before treatment in the two groups (P<0.05), and the grading in the observation group was superior to that in the control group (P<0.05); the dynamic view scores of the facial nerve function scoring system were increased compared with those before treatment in the two groups (P<0.05), and the score in the observation group was higher than that in the control group (P<0.05). The total effective rate was 91.7% (22/24) in the observation group, and that in the control group was 84.0% (21/25), there was no significant difference in the total effective rate between the two groups (P>0.05). The cure rate was 62.5% (15/24) in the observation group, which was higher than 20.0% (5/25) in the control group (P<0.05). CONCLUSION: On the basis of conventional acupuncture, acupuncture at infusion points of "four seas" can effectively treat refractory peripheral facial paralysis, improve the facial nerve function and increase the cure rate.

Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses.

Canagliflozin (CFZ) is a sodium-glucose cotransporter-2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC-MS/MS). A non-compartmental analysis revealed key pharmacokinetic parameters, including a median Tmax of 7 h, a Cmax of 2350 ng/mL, and a t1/2Z of 28.5 h. CFZ treatment reduced glucose (AUCGLU, p = 0.001) and insulin (AUCINS, p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.

Phytogenic effects of Marrubium vulgare on the growth performance of weaned piglets: biochemical parameters and liquid chromatographic-electrospray ionization-mass spectrometric profile of plant and animal serum.

BACKGROUND: Multidrug-resistant bacteria in humans have prompted the search for alternative solutions derived from herbal medicines that can substitute antibiotics in livestock production. Thus, the goal of this study was to evaluate the phytogenic properties of Marrubium vulgare infusion (MVI) on weaned pigs. Thirty animals were randomly divided into five groups of six animals, each receiving a physiological solution, clenbuterol and the infusion extract at doses of 0.01 (MVI 1%), 0.1 (MVI 10%) and 0.2 (MVI 20%) mg kg-1 for 28 days. Biochemical parameters and the liquid chromatographic-electrospray ionization-mass spectrometric (LC-ESI-MS) chemical profiles of the infusion extract and animal serum were studied. RESULTS: The doses MVI 1 and 10% led to weight gain higher than the controls. No significant changes were noted in the biochemical parameters including erythrocytes, hemoglobin, hematocrit, mean corpuscular volume and others. Evaluation of enzymatic levels in blood revealed no significant changes. LC-ESI-MS data of MVI showed the presence of 34 secondary metabolites, and successive chromatographic purification of MVI yielded marrubiin and apigenin as major components. LC-ESI-MS data of animal serum showed the presence of a diterpene, a flavonoid and diverse cholic acid derivatives. CONCLUSION: Results indicated the doses MVI 1 and 10% promote weight gain with no significant alterations in blood biochemicals, and liver and kidney function. © 2024 Society of Chemical Industry.

A single-centre study on abnormal antinuclear antibodies in children caused by intravenous infusion of gamma globulin.

Objective: To clarify the impact of intravenous infusion of gamma globulin (IVIg) on antinuclear antibodies (ANAs) in children. Methods: A retrospective analysis was performed on the data of children with nonspecific autoantibody-related diseases whose antinuclear antibody (ANA) and autoantibody profiles were detected in our hospital from January to March 2022. A total of 108 patients with a clear history of IVIg infusion within 28 days composed the IVIg group, and 1201 patients without a history of IVIg infusion composed the non-IVIg group. Results: All patients in the IVIg group had either positive ANAs or positive autoantibodies. Anti-SSA, anti-Ro52 and anti-AMA Mi2 were the top three autoantibodies in the IVIg group. The proportions of patients who were positive for either of these three autoantibodies in the IVIg group were significantly greater than those in the non-IVIg group (all P<0.5). Spearman correlation analysis revealed that the signal intensities of anti-SSA and anti-Ro52 were negatively correlated with the number of days of ANA detection after IVIg infusion (P<0.05). Multiple logistic analyses revealed that a greater total dosage of IVIg, greater IVIg per kilogram of body weight, and fewer ANA detection days after IVIg infusion were independent risk factors for positive anti-SSA and anti-Ro52 results. Conclusions: It is recommended that if rheumatic diseases are suspected, ANA detection should be carried out beforeIVIg infusion. But for patients who are positive for at least one of these three autoantibodies after IVIg infusion, doctors should first consider adoptive antibodies.

Minor histocompatibility antigens to predict, monitor or manipulate GvL and GvHD after allogeneic hematopoietic cell transplantation.

Allogeneic hematopoietic cell transplantation (alloHCT) provides a potential curative treatment for haematological malignancies. The therapeutic Graft-versus-Leukaemia (GvL) effect is induced by donor T cells attacking patient hematopoietic (malignant) cells. However, if healthy non-hematopoietic tissues are targeted, Graft-versus-Disease (GvHD) may develop. After HLA-matched alloHCT, GvL and GvHD are induced by donor T cells recognizing polymorphic peptides presented by HLA on patient cells, so-called minor histocompatibility antigens (MiHAs). The balance between GvL and GvHD depends on the tissue distribution of MiHAs and T-cell frequencies targeting these MiHAs. T cells against broadly expressed MiHAs induce GvL and GvHD, whereas those targeting MiHAs with hematopoietic-restricted expression induce GvL without GvHD. Recently, the MiHA repertoire identified in natural immune responses after alloHCT was expanded to 159 total HLA-I-restricted MiHAs, including 14 hematopoietic-restricted MiHAs. This review explores their potential relevance to predict, monitor, and manipulate GvL and GvHD for improving clinical outcome after HLA-matched alloHCT.

Ultrasound assessment of short peripheral catheter failure.

INTRODUCTION: Short peripheral catheters (SPCs) are affected by a high complication rate that leads to catheter failure. Currently, the Visual Infusion Phlebitis score (VIP) is the most used tool to verify the presence of inflammatory complications (phlebitis and thrombophlebitis). However, ultrasound signs (US) may be an attractive alternative. OBJECTIVE: This study aims to evaluate the sensitivity and specificity of US and VIP score = 1 in identifying and recognizing early signs of SPC failure. The time to positivity for US and VIP scores was assessed as a secondary outcome. METHODS: An observational prospective study was conducted. In each patient, US (subcutaneous edema; fibroblastic sleeve; thrombophlebitis) and VIP of the exit site were performed every 24 h until 96 h after insertion. Compared to catheter failure, Sensitivity, Specificity, and Predictive values in both US and VIP were calculated. RESULTS: Two hundred patients were enrolled. The presence of ultrasonic pattern suggestive of edema at 72 h (p = 0.018), fibroblastic sleeve at 24, 48, 72, and 96 h (p < 0.001), thrombosis at 48 (p < 0.001) and 72 h (p = 0.005), and at least one of an abovementioned US at all checkpoints (p < 0.001) were highly significant predictors of complications. Both US and VIP effectively detect inflammatory events; however, the US showed better sensitivity in overall checkpoints and earlier predictive ability than VIP (1.9 vs 0.47 days). CONCLUSIONS: An ultrasound inflammatory pattern is correlated with SPC failure. An ultrasound protocol-requiring minimal training-is more effective than VIP in recognizing early signs of device failure.

Thiopentone-based total intravenous anaesthesia for a patient with carnitine palmitoyltransferase II deficiency and malignant hyperthermia susceptibility.

In this case report, we discuss the use of a thiopentone infusion for the maintenance of anaesthesia in a patient with confirmed malignant hyperthermia susceptibility and carnitine palmitoyltransferase 2 deficiency. The concurrence of both diagnoses precluded the use of both propofol-based total intravenous anaesthesia and volatile inhalational anaesthesia. This patient had been anaesthetised previously with a triple infusion regimen of thiopentone, midazolam and remifentanil and this was a unique opportunity to compare the two instances. Electroencephalogram-based depth of anaesthesia monitoring was in routine use by the time of the second anaesthetic, and thus, the thiopentone infusion could be adjusted accordingly, resulting in a more rapid emergence time. We hope that this case may serve as an example of suitable anaesthetic alternative should both propofol infusion and inhalational anaesthesia not be an option.

Digital subtraction angiography-guided pancreatic arterial infusion of GEMOX chemotherapy in advanced pancreatic adenocarcinoma: a phase II, open-label, randomized controlled trial comparing with intravenous chemotherapy.

BACKGROUND: Advanced pancreatic adenocarcinoma lacks effective treatment options, and systemic gemcitabine-based chemotherapy offers only marginal survival benefits at the cost of significant toxicities and adverse events. New therapeutic options with better drug availability are warranted. This study aims to evaluate the safety and efficacy of digital subtraction angiography (DSA)-guided pancreatic arterial infusion (PAI) versus intravenous chemotherapy (IVC) using the gemcitabine and oxaliplatin (GEMOX) regimen in unresectable locally advanced or metastatic pancreatic cancer (PC) patients. MATERIALS AND METHODS: This study prospectively enrolled 51 eligible treatment-naive patients with unresectable PC to receive GEMOX treatment via PAI or IVC (1:1 ratio randomization) from December 2015 to December 2019. Cycles were repeated monthly, and each process consisted of two treatments administered bi-weekly. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), 1-year survival, 6-month survival, tumor-site subgroup survival, and incidences of adverse events were compared. RESULTS: The median OS of the PAI and IVC groups were 9.93 months and 10.07 months, respectively (p = 0.3049). The median PFS of the PAI and IVC groups were 5.07 months and 4.23 months (p = 0.1088). No significant differences were found in the ORR (11.54% vs. 4%, p = 0.6312), DCR (53.85% vs. 44%, p = 0.482), and 1-year OS rate (44% vs. 20.92%, p = 0.27) in PAI and IVC groups. The 6-month OS rate was significantly higher in the PAI group (100%) than in the IVC group (83.67%) (p = 0.0173). The median OS of patients in PAI group with pancreatic head and neck tumors were significantly higher than those of body and tail tumors (12.867 months vs. 9 months, p = 0.0214). The incidences of hematologic disorders, liver function disorders, and digestive disorders in the IVC group were higher than in the PAI group (p < 0.05). CONCLUSION: GEMOX PAI therapy presented a higher 6-month OS rate and fewer adverse events than IVC in advanced pancreatic adenocarcinoma patients. Those with pancreatic head and neck tumors may yield a superior treatment outcome from PAI treatment. TRIAL REGISTRATION NUMBER: NCT02635971. DATE OF REGISTRATION: 21/12/2015.

Influence of continuous subcutaneous apomorphine infusion on cognition and behavior in Parkinson's disease: A systematic review.

INTRODUCTION: The efficacy of continuous subcutaneous apomorphine infusion (CSAI) for motor complications of Parkinson's disease (PD) is established. However, its effect on cognition and behavior remains controversial. The main objective of this systematic review was to describe the existing literature on the effects of CSAI on cognition and behavior and to determine the quality for each study. METHODS: PubMed/Medline, Embase, APA PsycInfo®, and Cochrane Library databases were searched, following PRISMA recommendations. Only longitudinal studies evaluating the effect of CSAI on cognition (global cognition, executive functions, visuospatial abilities, language, memory, attention, social cognition) and/or behavior (depression, anxiety, apathy, psychotic symptoms, impulse control disorders, neuropsychiatric fluctuations) in PD were included. The quality of the included studies was also assessed with a questionnaire. RESULTS: Twenty-three longitudinal studies evaluated the effect of CSAI on cognition and/or behavior. Overall, results were suggestive of positive effects, notably on executive functions and emotion recognition. However, there were some reports of cognitive slowing and long-term global cognitive deterioration. At the behavioral level, no study showed significant adverse effect of CSAI. Occasionally, a slight improvement of depression, anxiety, apathy, and neuropsychiatric fluctuations was reported. Nevertheless, only four studies met good quality criteria and controlled study regarding cognition were lacking. CONCLUSION: The results suggest that CSAI has no obvious negative effects on cognition and behavior in PD. This treatment even shows promise in reducing certain symptoms such as neuropsychiatric fluctuations. However, due to methodological limitations in many studies, no robust conclusions can be drawn. Further multicenter controlled trials are needed to confirm these results.

Hepatic arterial infusion of GEMOX plus systemic gemcitabine chemotherapy combined with lenvatinib and PD-1 inhibitor in large unresectable intrahepatic cholangiocarcinoma.

PURPOSE: To assess the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) of gemcitabine and oxaliplatin (GEMOX) plus systemic gemcitabine chemotherapy (GEM-SYS) in combination with lenvatinib and programmed cell death protein-1 (PD-1) inhibitor for patients with large unresectable intrahepatic cholangiocarcinoma (uICC). METHODS: From November 2019 to December 2022, 21 large uICC patients who underwent GEMOX-HAIC (Day 1) and GEM-SYS (Day 8) (3w/cycle) combined with lenvatinib and PD-1 inhibitor were retrospectively enrolled. Local tumor response, progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were analyzed. Tumor response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. AEs were evaluated by the common terminology criteria for adverse events (CTCAE) version 5.0. RESULTS: After a median follow-up duration of 16.0 months (range 5-43.5 months), 17 patients had died. The median OS was 19.5 months (range 9-43.5 months), and the median PFS was 6.0 months (range 2.5-38.5 months). The 1-, 2-, and 3-year OS rates were 71.4 %, 42.9 %, and 19.0 %, respectively. The 1-, 2-, and 3-year PFS rates were 33.3 %, 19.0 %, and 9.5 %, respectively. Complete response, partial response, stable disease, and progressive disease were observed in 0 (0 %), 11 (52.3 %), 5 (23.8 %), and 5 (23.8 %) patients, respectively. The disease control rate and objective response rate were 76.1 % and 52.3 %, respectively. None of the enrolled patients experienced grade 5 AEs. CONCLUSIONS: GEMOX-HAIC plus GEM-SYS in combination with lenvatinib and PD-1 inhibitor was effective and well tolerated for patients with large uICC.

Compatibility of medication admixtures in continuous subcutaneous infusions: prioritizing laboratory testing for common combinations.

OBJECTIVES: Continuous subcutaneous infusions (CSCIs) are indicated as an alternative therapy when the oral route is not viable. However, despite their widespread use in palliative care, the evidence for admixture compatibility remains a limitation. It is estimated that a significant number of admixtures used in practice are not supported by laboratory studies, which may lead to suboptimal clinical outcomes. The study aimed to determine the frequency of admixtures used in clinical practice without compatibility data generated by laboratory studies, and thereby identifying the most commonly prescribed admixtures that require laboratory data, which can help to guide the prioritization of future testing. METHODS: This study was conducted across five palliative care services (three inpatients and two communities) in Victoria, Australia between May and July 2021. Electronic or paper medication charts of CSCIs were reviewed across all participating sites for all infusions administered. Data collected included medication combinations, dose, diluent, final volume, duration of infusion, reports of infusion-related reactions, and observed incompatibility. KEY FINDINGS: A total of 616 infusions containing two to three medications were assessed. Only 60% of these infusions were validated by laboratory data. Eleven most commonly prescribed admixtures with no laboratory compatibility data were identified over the 3-month period. CONCLUSION: Laboratory testing for the identified admixtures should be advocated to promote the safe and effective use of these medications.

Performance of a Continuous Subcutaneous Insulin Infusion (CSII) Pump With Acoustic Volume and Flow Sensing in Simulated High-Consequence Situations.

Goal: An insulin pump's failure to deliver insulin in the right amount at the right time is a preventable cause of hospitalization. We evaluated key performance metrics of a novel insulin pump that prevents "silent insulin non-delivery" caused by blockage, delivery of air and site leakage. This is accomplished via an acoustic sensor that measures the volume of insulin delivered with each pulse in real-time. Methods: We tested long and short-term flow accuracy, occlusion-detection time and pressure, and air management of the new device (ND) versus 3 U.S. commercial insulin pumps (CIPs) using standardized methods. Results: The ND outperformed CIPs on long-term basal flow rate error. Occlusion detection was 5 to 22.5 times faster depending on the basal rate and resulted in significantly lower (2 to 5x) pressures at time of occlusion. With air included in the drug reservoir, the tested CIPs can infuse air without detection, while the ND prevented air delivery without interruption. Conclusions: Bench tests of the ND versus 3 commercially available pumps showed improved occlusion detection and air management without flow performance tradeoffs. Additionally, the lower delivery pressure measured at time of occlusion suggests a substantially lower potential for site leakage at both basal and bolus rates. These enhancements combine to decrease the likelihood of silent insulin non-delivery.

Continuous Insulin Therapy to Prevent Post-Transplant Diabetes Mellitus: A Randomized Controlled Trial.

Rationale & Objectives: Hyperglycemia is frequently observed early after transplantation and associated with development of post-transplant diabetes mellitus (PTDM). Here, we assessed continuous subcutaneous insulin infusion (CSII) targeting afternoon hyperglycemia. Study Design: Open-label randomized parallel 3-arm design. Settings & Participants: In total, 85 kidney transplant recipients without previous diabetes diagnosis were randomized to postoperative CSII therapy, basal insulin, or control. Interventions: Insulin was to be initiated at afternoon capillary blood glucose level of ≥140 mg/dL (7.8 mmol/L; CSII and basal insulin) or fasting plasma glucose level of ≥200 mg/dL (11.1 mmol/L; control). Outcomes: Hemoglobin A1c (HbA1c) levels at 3 months post-transplant (primary endpoint). PTDM assessed using oral glucose tolerance test at 12 and 24 months. Results: CSII therapy lasted until median day 18 and maximum day 88. The median HbA1c value at month 3 was 5.6% (38 mmol/mol) in the CSII group versus 5.7% (39 mmol/mol) in the control group (P = 0.70) and 5.4% (36 mmol/mol) in the basal insulin group (P = 0.02). At months 12 and 24, the odds for PTDM were similar compared with the control group (odds ratios [95% confidence intervals], 0.80 [0.18-3.49] and 0.71 [0.15-3.16], respectively) and the basal insulin group (0.96 [0.18-5.68] and 1.51 [0.24-12.84], respectively). Mild hypoglycemia events occurred in the CSII and the basal insulin groups. Limitations: This study is limited by outdated insulin pump technology, frequent discontinuations of CSII, a complex protocol, and concerns regarding reliability of HbA1c measurements. Conclusions: CSII therapy was not superior at reducing HbA1c levels at month 3 or PTDM prevalence at months 12 and 24 compared with the control or basal insulin group.

In-use stability of rituximab and IVIG during intravenous infusion: Impact of peristaltic pump, IV bags, flow rate, and plastic syringes.

This study investigates the impact of intravenous (IV) infusion protocols on the stability of Intravenous Immunoglobulin G (IVIG) and Rituximab, with a particular focus on subvisible particle generation. Infusion set based on peristaltic movement (Medifusion DI-2000 pump) was compared to a gravity-based infusion system (Accu-Drip) at different flow rates. The impacts of different diluents (0.9 % saline and 5.0 % dextrose) and plastic syringes with or without silicone oil (SO) were also investigated. The results from the aforementioned particular case demonstrated that peristaltic pumps generated high levels of subvisible particles (prominently < 25 µm), exacerbated by increasing flow rates, specifically in formulations lacking surfactants. Other factors, such as diluent type and syringe composition, also increased the number of subvisible particles. Strategies that can help overcome these complications include surfactant addition as well as the use of SO-free syringes and a gravity infusion system, which aid in reducing particle formation and preserving antibody monomer during administration. Altogether, these findings highlight the importance of the careful selection of formulations and infusion protocols to minimize particle generation during IV infusion both for patients' safety and treatment efficacy.