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Clinical Lymphoma, Myeloma & Leukemia Jun 2024Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Melflufen, a first-in-class alkylating peptide-drug conjugate, rapidly enters tumor cells and metabolizes to melphalan. In previous studies, melflufen was administered via central venous catheter (CVC). However, administration by peripheral venous catheter (PVC) may be preferable.
PATIENTS AND METHODS
PORT was a two-period, phase 2 crossover study of CVC versus PVC melflufen administration in patients with relapsed/refractory multiple myeloma. Adults with ≥ 2 prior therapies refractory to/intolerant of an immunomodulatory drug and a proteasome inhibitor were randomized 1:1 to weekly oral dexamethasone plus melflufen (40 mg) via CVC or PVC infusion on day 1 of 28-day cycle 1. In cycle 2, patients continued dexamethasone and crossed over to the other melflufen administration route. In cycle 3, all patients received melflufen until progression; PVC or CVC routes were allowed based upon investigator decision. Pharmacokinetic sampling was performed during and after melflufen infusion. Primary endpoints were melphalan pharmacokinetic parameters (C, AUC, and AUC) and frequency and severity of PVC-related local reactions.
RESULTS
The 90% CIs for adjusted geometric mean ratios for pharmacokinetic parameters following CVC versus PVC administration were within the 0.8-1.25 bioequivalence range (C 0.946 [90% CI: 0.849, 1.053]; AUC 0.952 [90% CI: 0.861, 1.053]; AUC 0.955 [90% CI: 0.863, 1.058]). In both arms, adverse events were primarily hematological and similar; no phlebitis or local infusion-related reactions occurred.
CONCLUSION
Melflufen PVC and CVC administrations are bioequivalent based on melphalan pharmacokinetic parameters. Melflufen via PVC was well tolerated, with no infusion-related reactions or new safety signals and may represent an alternative route of administration.
Topics: Humans; Multiple Myeloma; Male; Female; Middle Aged; Aged; Cross-Over Studies; Phenylalanine; Adult; Melphalan; Neoplasm Recurrence, Local; Administration, Intravenous; Aged, 80 and over; Treatment Outcome; Infusions, Intravenous
PubMed: 38490927
DOI: 10.1016/j.clml.2024.02.012 -
Australasian Emergency Care Mar 2024Hospitals frequently introduce new medical devices. However, the process of clinicians adapting to these new vascular access devices has not been well explored. The...
BACKGROUND
Hospitals frequently introduce new medical devices. However, the process of clinicians adapting to these new vascular access devices has not been well explored. The study aims to explore clinicians' experience with the insertion of a new guidewire peripheral intravenous catheter (PIVC) introduced in the emergency department (ED) setting.
METHODS
The study was conducted at two EDs in Queensland, Australia, utilising a qualitative explorative approach. Interviews were conducted with guidewire PIVC inserters, including ED doctors and nurses, and field notes were recorded by research nurses during insertions. Data analysis was performed using inductive content analysis, from which themes emerged.
RESULTS
The study compiled interviews from 10 participants and field notes from 191 observation episodes. Five key themes emerged, including diverse experience, barriers related to the learning process, factors influencing insertion success, and recommendations to enhance clinicians' acceptance. These themes suggest that the key to successful adoption by clinicians lies in designing user-friendly devices that align with familiar insertion techniques, facilitating a smooth transfer of learning.
CONCLUSION
Clinician adaptation to new devices is vital for optimal patient care. Emergency nurses and doctors prefer simplicity, safety, and familiarity when it comes to new devices. Providing comprehensive device training with diverse training resources, hands-on sessions, and continuous expert support, is likely to enhance clinician acceptance and the successful adoption of new devices in ED settings.
PubMed: 38490874
DOI: 10.1016/j.auec.2024.03.001 -
Cancer Medicine Feb 2024Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification.
METHODS
This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis.
RESULTS
Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%).
CONCLUSIONS
Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.
Topics: Humans; Cisplatin; Furosemide; Mannitol; Phlebitis; Prospective Studies; Thoracic Neoplasms
PubMed: 38457231
DOI: 10.1002/cam4.6839 -
Frontiers in Cellular and Infection... 2024() infection is rare in pediatrics. In addition, the detection time of by blood culture is long, and the positive rate is low. Infection with bacilli usually follows...
() infection is rare in pediatrics. In addition, the detection time of by blood culture is long, and the positive rate is low. Infection with bacilli usually follows rapid disease progression, resulting in high mortality. In previous reports of -related cases, the most dangerous moment of the disease occurred after the appearance of Lemierre's syndrome. We report an atypical case of a 6-year-old female patient who developed septic shock within 24 h of admission due to infection in the absence of Lemierre's syndrome. was identified in a blood sample by metagenomics next-generation sequencing (mNGS) but not by standard blood culture. The patient was finally cured and discharged after receiving timely and effective targeted anti-infection treatment. In the present case study, it was observed that the heightened virulence and invasiveness of contribute significantly to its role as a primary pathogen in pediatric septic shock. This can precipitate hemodynamic instability and multiple organ failure, even in the absence of Lemierre's syndrome. The use of mNGS can deeply and rapidly identify infectious pathogens, guide the use of targeted antibiotics, and greatly improve the survival rate of patients.
Topics: Female; Humans; Child; Shock, Septic; Fusobacterium necrophorum; Lemierre Syndrome; High-Throughput Nucleotide Sequencing; Anti-Bacterial Agents
PubMed: 38435306
DOI: 10.3389/fcimb.2024.1236630 -
Journal of Vascular Surgery. Venous and... Jul 2024Recanalization of target veins after treatment of superficial venous incompetence has clinical implications and may depend on the type of intervention. The aim of this...
BACKGROUND
Recanalization of target veins after treatment of superficial venous incompetence has clinical implications and may depend on the type of intervention. The aim of this study was to evaluate patient and procedural factors associated with truncal vein recanalization in a large study cohort using the Vascular Quality Initiative (VQI) Varicose Vein Registry.
METHODS
We performed a retrospective review using the VQI Varicose Vein Registry from 2014 to 2018. We evaluated all procedures performed for truncal venous insufficiency. Demographic data and information about treatment modality were collected. Patients were separated into recanalization and nonrecanalization groups based on the status of the treated vein at follow-up ultrasound examination. The vein was only considered recanalized if the VQI noted complete recanalization of the target vein. Univariate and multivariate comparisons were performed as appropriate.
RESULTS
A total of 10,604 procedures were performed in 7403 patients. The average age was 55.9 years and 70.3% of the patients were female. Patients with recanalization were more likely to have a history of phlebitis (P < .001) and had a higher mean body mass index (30.5 vs 32., kg/m ; P = .006) compared with those without recanalization. There was no difference in the use of compression therapy, anticoagulation, deep venous reflux, number of pregnancies, prior deep vein thrombosis, Venous Clinical Severity Score, and clinical-etiology-anatomy-pathophysiology between patients with and without recanalization. The number of truncal veins treated per procedure was higher in the recanalization group compared with the nonrecanalization group (2.36 vs 1.88; P = .001). After multivariate logistic regression, laser ablation was associated with higher rate of recanalization compared with radiofrequency ablation (P = .017).
CONCLUSIONS
This study is the first to use VQI based data to describe risk factors for recanalization following treatment of truncal venous reflux. The use of laser ablation for truncal veins is associated with a higher risk for recanalization compared with radiofrequency ablation. Obesity, prior phlebitis, and number of veins treated were independently associated with increased rate of recanalization.
Topics: Humans; Female; Male; Retrospective Studies; Middle Aged; Risk Factors; Venous Insufficiency; Treatment Outcome; Varicose Veins; Registries; Aged; Risk Assessment; Endovascular Procedures; Adult; Time Factors; Catheter Ablation
PubMed: 38428500
DOI: 10.1016/j.jvsv.2024.101860 -
Journal of Infusion Nursing : the...Complications of peripheral intravenous catheters (PIVCs) remain a major contributor to health care costs and are a patient safety problem. The objective of this...
Complications of peripheral intravenous catheters (PIVCs) remain a major contributor to health care costs and are a patient safety problem. The objective of this cross-sectional descriptive study was to examine the prevalence of complications and factors associated with complications from peripheral intravenous fluid administration. The study was conducted at a tertiary care hospital in Thailand. The instruments were developed from the literature review. Data were analyzed using SPSS statistics, version 22. The study examined 441 patients with a total of 497 PIVC sites. Phlebitis (level 1 and 2 only) occurred at 2.41% of all sites; infiltration (level 1 and 2 only) occurred at 1.01% of all sites, and extravasation (mild and moderate only) occurred at 0.60% of all sites. Factors associated with the occurrence of infiltration complications included receiving intravenous (IV) crystalloids (P = .03) and receiving IV analgesic drugs (P = .001). Age was statistically significantly related to extravasation complications (P = .001). Nurses should be aware of possible complications from peripheral intravenous fluid administration, especially in older patients and those receiving IV crystalloids or analgesic drugs.
Topics: Aged; Humans; Analgesics; Catheterization, Peripheral; Cross-Sectional Studies; Prevalence; Thailand; Tertiary Care Centers
PubMed: 38422405
DOI: 10.1097/NAN.0000000000000538 -
Drug Discoveries & Therapeutics Mar 2024In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch...
Comparison of the physicochemical properties of branded and generic glucose-added maintenance hypotonic infusion fluids to assess the potential for phlebitis and incompatibility with other drugs.
In Japan, the switch from branded to generic infusion fluids has been promoted as a national policy. Recently, as generic products have been in short supply, the switch from generic to branded infusion fluids has increased. However, certain additives for injectable infusion fluids, such as nonvolatile acids like acetic acid and hydrochloric acid, are not required to be listed in the package insert. We hypothesized that the addition of nonvolatile acids may be one of the reasons for the differences in physicochemical properties between the branded and generic infusion fluids. We have previously reported that in other types of electrolyte infusion fluids, a variation in pH can cause incompatibility with other drugs, and variation in titratable acidity and osmolality can lead to phlebitis. Glucose-added maintenance hypotonic infusion fluid (listed as type-3G) is commonly used as a maintenance solution when energy support is needed. However, nonvolatile acid is added to prevent the caramelization of glucose, resulting in higher osmolality and titratable acidity and lower pH. Therefore, we hypothesized that both phlebitis and incompatibility with other drugs are likely to occur; hence, we measured and evaluated the physicochemical properties of branded and generic type-3G infusion fluids. We show that the osmolality, pH, and titratable acidity of all evaluated branded and generic products differed significantly and that these properties should be evaluated together to avoid phlebitis and incompatibility with other drugs when switching between branded and generic type-3G infusion fluids.
Topics: Humans; Phlebitis; Glucose; Drugs, Generic; Japan
PubMed: 38382993
DOI: 10.5582/ddt.2023.01091 -
Arthritis Research & Therapy Feb 2024IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the...
OBJECTIVES
IgG4-related disease (IgG4-RD) is a systemic autoimmune disease with an unknown etiology, affecting single/multiple organ(s). Pathological findings include the infiltration of IgG4-producing plasma cells, obliterative phlebitis, and storiform fibrosis. Although immunological studies have shed light on the dysregulation of lymphocytes in IgG4-RD pathogenesis, the role of non-immune cells remains unclear. This study aimed to investigate the demographics and characteristics of non-immune cells in IgG4-RD and explore potential biomarkers derived from non-immune cells in the sera.
METHODS
We conducted single-cell RNA sequence (scRNA-seq) on non-immune cells isolated from submandibular glands of IgG4-RD patients. We focused on fibroblasts expressing collagen type XV and confirmed the presence of those fibroblasts using immunohistochemistry. Additionally, we measured the levels of collagen type XV in the sera of IgG4-RD patients.
RESULTS
The scRNA-seq analysis revealed several distinct clusters consisting of fibroblasts, endothelial cells, ductal cells, and muscle cells. Differential gene expression analysis showed upregulation of COL15A1 in IgG4-RD fibroblasts compared to control subjects. Notably, COL15A1-positive fibroblasts exhibited a distinct transcriptome compared to COL15A1-negative counterparts. Immunohistochemical analysis confirmed a significant presence of collagen type XV-positive fibroblasts in IgG4-RD patients. Furthermore, immune-suppressive therapy in active IgG4-RD patients resulted in decreased serum levels of collagen type XV.
CONCLUSIONS
Our findings suggest that collagen type XV-producing fibroblasts may represent a disease-characterizing non-immune cell population in IgG4-RD and hold potential as a disease-monitoring marker.
Topics: Humans; Immunoglobulin G4-Related Disease; Submandibular Gland; Endothelial Cells; Fibroblasts; Collagen; Sequence Analysis, RNA
PubMed: 38378635
DOI: 10.1186/s13075-024-03289-7 -
Heliyon Feb 2024We report a case of immunoglobulin (ig)-g4-related thyroiditis associated with graves' disease. a 45-year-old man was diagnosed with graves' disease due to asymptomatic...
We report a case of immunoglobulin (ig)-g4-related thyroiditis associated with graves' disease. a 45-year-old man was diagnosed with graves' disease due to asymptomatic enlarged thyroid gland and high serum levels of thyrotropin receptor antibodies and thyroid hormones. surgical resection of the thyroid gland was performed because of further thyroid gland enlargement and severe fluctuations in the thyroid hormonal levels, despite medical therapy with a combination of an antithyroid drug and a thyroid hormone preparation. macroscopic examination of the resected thyroid gland revealed a grayish-white diffuse swelling, and histopathological findings revealed follicular destruction, chronic inflammatory cell infiltration with diffuse igg4-positive plasma cells (IgG4/IgG >40%), storiform fibrosis, and phlebitis obliterans throughout the thyroid tissue. Additionally, there were small foci of high columnar follicular components with scalloping, resembling Graves' disease. We propose that all patients with Graves' disease should be evaluated for coexisting IgG4-related thyroiditis to detect ophthalmopathies as soon as possible.
PubMed: 38375285
DOI: 10.1016/j.heliyon.2024.e25843 -
Medicine Feb 2024Lemierre-like syndrome (LLS) is characterized by bacteremia, septic thrombophlebitis of the internal jugular vein, and metastatic abscesses. In contrast to classic... (Review)
Review
RATIONALE
Lemierre-like syndrome (LLS) is characterized by bacteremia, septic thrombophlebitis of the internal jugular vein, and metastatic abscesses. In contrast to classic Lemierre syndrome, sources of infection are not related to oropharyngeal infections, as are frequent soft tissue infections. In recent years, Staphylococcus aureus has been identified as an emergent pathogen that causes this syndrome. The mortality rate of LLS caused by this pathogen is approximately 16%. Timely diagnosis, antibiotic treatment, and infection control are the cornerstones to treat LLS. Anticoagulant therapy as adjuvant treatment remains controversial.
PATIENT CONCERNS
A 31-year-old woman from California, United States (US), was admitted to the emergency room with a history of 2 days of fever and severe throbbing pain in the left cervical region. Thorax and neck CT tomography revealed confluent cavities suggestive of septic embolism in the lungs and a filiform thrombus in the lumen of the left internal jugular vein, with moderate swelling of the soft and muscular tissues. Methicillin-resistant Staphylococcus aureus (MRSA) was isolated from the blood culture.
DIAGNOSIS
The thrombus in the internal jugular vein associated with cellulitis in the neck and multiple cavitary lesions in the lungs support the diagnosis of LLS caused by MRSA with septic embolization.
INTERVENTIONS
During treatment, the patient received vancomycin IV for 25 days and returned to the US with linezolid orally. In addition, assisted video-thoracoscopy and bilateral mini-thoracotomy with pleural decortication were performed for infectious source control, where 1700cc of purulent pleural fluid was drained.
OUTCOMES
The patient was discharged with optimal evolution.
LESSONS
LLS should be suspected in patients with skin and soft tissue infections who develop thrombosis or metastatic infections. MRSA infections should be considered in patients from areas where this pathogen is prevalent.
Topics: Female; Humans; Adult; Lemierre Syndrome; Methicillin-Resistant Staphylococcus aureus; Soft Tissue Infections; Thrombophlebitis; Staphylococcus aureus; Anti-Bacterial Agents
PubMed: 38363930
DOI: 10.1097/MD.0000000000037006