-
Expert Opinion on Pharmacotherapy Aug 2017Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal... (Review)
Review
Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell proliferation and overproduction of monoclonal paraprotein, hypercalcemia, renal failure, anemia, osteolytic bone lesions, and infections. Melphalan, a nitrogen mustard, is an alkylating agent synthesized in 1953, and it has been used in multiple myeloma therapy for fifty years. Although novel agents have been introduced in the past few decades improving prognosis of the disease, melphalan still maintains a crucial role in the treatment of MM acting both as cytotoxic agent through damage to DNA, and as immunostimulatory drug by inhibiting Interleukin-6, as well as interaction with dendritic cells, and immunogenic effects in tumor microenvironment. Areas covered: This review focuses on available data about melphalan pharmacology and its role in clinical practice. Expert opinion: Melphalan remains crucial in therapy of multiple myeloma because of its good manageability, safety profile, efficacy, and economic sustainability. These characteristics make it pivotal also for new regimens in combination with novel agents.
Topics: Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials as Topic; Humans; Interleukin-6; Melphalan; Molecular Structure; Multiple Myeloma; Myeloma Proteins; Prognosis
PubMed: 28658983
DOI: 10.1080/14656566.2017.1349102 -
Pediatric Surgery International Jun 2022We aimed to evaluate a complicated appendicitis clinical practice guideline at our institution.
PURPOSE
We aimed to evaluate a complicated appendicitis clinical practice guideline at our institution.
METHODS
Records were compared before and after protocol implementation. We standardized an ED consult pathway, antibiotic use and need for early appendectomy (EA) versus interval appendectomy (IA). We evaluated demographics, clinical characteristics, and outcomes. Subgroup analysis was performed to compare patients with small abscess treated with IA pre-protocol versus similar patients treated by EA post-protocol.
RESULTS
In total 246 patients were reviewed (Pre-protocol = 152, Post-protocol = 94). Pre-protocol early appendectomy rate was 51% versus 82% on post-protocol patients. There were no differences in demographics. Post-protocol the use of preoperative imaging significantly decreased (Pre 92% vs. 56%, p = 0.0001), as well as the use of discharge antibiotics (Pre 93% vs. Post 27%, p = 0.0001) with no change in abscess rate. Overall, post-protocol patients had fewer total CT scans performed (Pre 40% vs. Post 28%, p = 0.03) and decreased total length of stay (Pre 7.7 vs. Post 6.5 days, p = 0.049). On subgroup analysis, post-protocol EA with no or small abscess had lower median number of admissions, decreased total LOS (Pre IA 9 days vs. Post EA 5 days, p = 0.00001) and fewer complications (Pre IA 42% vs. EA 22%, p = 0.022).
CONCLUSION
The establishment of a standardized pediatric complicated appendicitis protocol may lead to improved outcomes and resource utilization. Patients presenting with no or small abscess may be the least likely to benefit from interval appendectomy.
LEVEL OF EVIDENCE
Level III.
Topics: Abscess; Anti-Bacterial Agents; Appendectomy; Appendicitis; Child; Humans; Length of Stay; Retrospective Studies
PubMed: 35396951
DOI: 10.1007/s00383-022-05124-z -
Indian Journal of Pediatrics Jan 2019CNS infections in children are medical emergency and are associated with high mortality and morbidity. For diagnosis, a high index of suspicion is required. Clinical... (Review)
Review
CNS infections in children are medical emergency and are associated with high mortality and morbidity. For diagnosis, a high index of suspicion is required. Clinical assessment should be supplemented by laboratory investigations including CSF Gram stain and cultures, blood culture, PCR on CSF, serological tests, and imaging. Commonly associated life threatening complications include coma, seizure, raised intracranial pressure (ICP), focal deficits, shock, respiratory failure, and fluid and electrolyte abnormalities. Immediate management should first address control of airway, breathing and circulation; protocolized management of raised ICP and status epilepticus; maintaining adequate intravascular volume; and close monitoring for early detection of complications. Appropriate antimicrobial agents should be administered promptly according to the suspected pathogen. Clinical evaluation, laboratory workup, specific antimicrobial therapy, supportive treatment, and management of associated complications should go hand in hand in a protocolized way for better outcome.
Topics: Anti-Infective Agents; Anticonvulsants; Central Nervous System Infections; Chemoprevention; Child; Electroencephalography; Fluid Therapy; Glucocorticoids; Glycerol; Hematologic Tests; Humans; Incidence; Intracranial Hypertension; Neuroimaging; Respiration, Artificial; Seizures; Spinal Puncture; Vaccination
PubMed: 29333566
DOI: 10.1007/s12098-017-2583-y -
Trauma Monthly Aug 2015The main objectives of triage are securing patient safety during the process of emergency diagnosis and treatment, and reduction of waiting time for medical services and... (Review)
Review
CONTEXT
The main objectives of triage are securing patient safety during the process of emergency diagnosis and treatment, and reduction of waiting time for medical services and transport. To date, there is no triage system for nerve agent victims.
EVIDENCE ACQUISITION
This systematic review proposes a new triage system for patients exposed to nerve agents. Information regarding clinical signs and symptoms of intoxication with nerve agents, primary treatments, and classification of patients were extracted from the literature. All related articles were reviewed. Subsequently, specialists from different disciplines were invited to discuss and draft protocols.
RESULTS
Finalized triage tables summarizing the classification methods and required protocols in the field were designed after several meetings.
CONCLUSIONS
The proposed triage protocol encompasses aspects from most of the existing triage systems to create a single overarching guide for unifying the triage process. The proposed protocol can serve as a base for the designing future guidelines.
PubMed: 26543836
DOI: 10.5812/traumamon.16211 -
Journal of Clinical Pharmacy and... May 2022Betalactam antibiotics are the most frequent cause of hypersensitivity reactions. Rapid drug desensitization (RDD) is a technique that induces temporary tolerance to a...
WHAT IS KNOWN AND OBJECTIVE
Betalactam antibiotics are the most frequent cause of hypersensitivity reactions. Rapid drug desensitization (RDD) is a technique that induces temporary tolerance to a drug allowing a patient to receive the optimal agent. The increased use of RDD and the lack of standardization among available protocols in terms of formulation, starting dose, number of steps and dosing frequency make it essential to determine the safety and appropriate management of these protocols, especially regarding reconstitution, diluents, stability and drug administration in order to guarantee reproducibility. We reviewed betalactam desensitization protocols in a tertiary hospital, in accordance with currently published practices and evaluated its use on patients over a period of three years.
METHODS
(a) We performed a literature search in PubMed, MEDLINE and Google Scholar databases for case reports and/or systematic reviews describing desensitization protocols for betalactam antibiotics. Pharmacokinetic parameters and physicochemical stability were checked for each antibiotic. (b) We retrospectively reviewed inpatients undergoing our antibiotic desensitization protocols from February 2018 to January 2021. Data and outcomes of desensitization procedures were analysed.
RESULTS
We developed nine RDD protocols: meropenem, ceftriaxone, ceftazidime, ampicillin, ceftolozane/tazobactam, cloxacillin, piperacillin/tazobactam, amoxicillin/clavulanate and penicillin G sodium. Five antibiotics have RDD protocols for two different doses, adjusted to patients with impaired renal function. Detailed data (diluent, total dose, volume, concentrations, duration and stability) of the protocol of each antibiotic used are provided. 28 desensitizations were performed in 17 patients, three of them with confirmed allergies by skin test. 26 out of 28 (92.9%) of them were successfully completed, including those three with positive skin results. The pathogens most frequently involved were E. faecalis and P. aeruginosa; both frequently associated with bacterial resistance. Meropenem, ceftriaxone and ceftazidime were the antibiotics most desensitized. 25 out of 26 (96.1%) procedures were successful in resolving the infection.
WHAT IS NEW AND CONCLUSIONS
Detailed information about compounding, dilution and stability is crucial to ensure safe and successful desensitization processes, as well as good coordination between the Allergy and Pharmacy departments. The increase in bacterial resistance to many of the commercially available antibiotics limits the therapeutic options for treating multidrug-resistant infections; in those situations, antibiotic desensitization may be a key therapeutic option. Although there is a broad consensus in limiting the use of RDD to patients with confirmed allergy, in usual clinical practice its application in those strongly suspected of having type I hypersensitivity is still observed. Our betalactam desensitization protocols have shown themselves to be safe and effective, as evidenced by data from the 17 patients on whom they have been tested.
Topics: Anti-Bacterial Agents; Ceftazidime; Ceftriaxone; Drug Hypersensitivity; Humans; Meropenem; Reproducibility of Results; Retrospective Studies; Review Literature as Topic; Tazobactam
PubMed: 34820864
DOI: 10.1111/jcpt.13578 -
Sensors (Basel, Switzerland) Jun 2022Recently, the Internet of Things (IoT) has emerged as an important way to connect diverse physical devices to the internet. The IoT paves the way for a slew of new...
Recently, the Internet of Things (IoT) has emerged as an important way to connect diverse physical devices to the internet. The IoT paves the way for a slew of new cutting-edge applications. Despite the prospective benefits and many security solutions offered in the literature, the security of IoT networks remains a critical concern, considering the massive amount of data generated and transmitted. The resource-constrained, mobile, and heterogeneous nature of the IoT makes it increasingly challenging to preserve security in routing protocols, such as the routing protocol for low-power and lossy networks (RPL). RPL does not offer good protection against routing attacks, such as rank, Sybil, and sinkhole attacks. Therefore, to augment the security of RPL, this article proposes the energy-efficient multi-mobile agent-based trust framework for RPL (MMTM-RPL). The goal of MMTM-RPL is to mitigate internal attacks in IoT-based wireless sensor networks using fog layer capabilities. MMTM-RPL mitigates rank, Sybil, and sinkhole attacks while minimizing energy and message overheads by 25-30% due to the use of mobile agents and dynamic itineraries. MMTM-RPL enhances the security of RPL and improves network lifetime (by 25-30% or more) and the detection rate (by 10% or more) compared to state-of-the-art approaches, namely, DCTM-RPL, RBAM-IoT, RPL-MRC, and DSH-RPL.
Topics: Internet of Things; Prospective Studies; Trust
PubMed: 35746321
DOI: 10.3390/s22124539 -
Journal of Visualized Experiments : JoVE Aug 2023Neutrophil extracellular traps (NETs) are released by neutrophils as a response to bacterial infection or traumatic tissue damage but also play a role in autoimmune...
Neutrophil extracellular traps (NETs) are released by neutrophils as a response to bacterial infection or traumatic tissue damage but also play a role in autoimmune diseases and sterile inflammation. They are web-like structures composed of double-stranded DNA filaments, histones, and antimicrobial proteins. Once released, NETs can trap and kill extracellular pathogens in blood and tissue. Furthermore, NETs participate in homeostatic regulation by stimulating platelet adhesion and coagulation. However, the dysregulated production of NETs has also been associated with various diseases, including sepsis or autoimmune disorders, which makes them a promising target for therapeutic intervention. Apart from electron microscopy, visualizing NETs using immunofluorescence imaging is currently one of the only known methods to demonstrate NET interactions in tissue. Therefore, various staining methods to visualize NETs have been utilized. In the literature, different staining protocols are described, and we identified four key components showing high variability between protocols: (1) the types of antibodies used, (2) the usage of autofluorescence-reducing agents, (3) antigen retrieval methods, and (4) permeabilization. Therefore, in vitro immunofluorescence staining protocols were systemically adapted and improved in this work to make them applicable for different species (mouse, human) and tissues (skin, intestine, lung, liver, heart, spinal disc). After fixation and paraffin-embedding, 3 µm thick sections were mounted onto slides. These samples were stained with primary antibodies for myeloperoxidase (MPO), citrullinated histone H3 (H3cit), and neutrophil elastase (NE) according to a modified staining protocol. The slides were stained with secondary antibodies and examined using a widefield fluorescence microscope. The results were analyzed according to an evaluation sheet, and differences were recorded semi-quantitatively. Here, we present an optimized NET staining protocol suitable for different tissues. We used a novel primary antibody to stain for H3cit and reduced non-specific staining with an autofluorescence-reducing agent. Furthermore, we demonstrated that NET staining requires a constant high temperature and careful handling of samples.
Topics: Humans; Animals; Mice; Extracellular Traps; Histones; Diagnostic Imaging; Fluorescent Antibody Technique; Neutrophils; Antibodies; Coloring Agents; Autoimmune Diseases
PubMed: 37677039
DOI: 10.3791/65272 -
EuroIntervention : Journal of EuroPCR... Feb 2022Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using... (Review)
Review
BACKGROUND
Coronary vasomotor dysfunction can be diagnosed in a large proportion of patients with angina in the presence of non-obstructive coronary artery disease (ANOCA) using comprehensive protocols for coronary vasomotor function testing (CFT). Although consensus on diagnostic criteria for endotypes of coronary vasomotor dysfunction has been published, consensus on a standardised study testing protocol is lacking.
AIMS
In this review we provide an overview of the variations in CFT used and discuss the practical principles and pitfalls of CFT.
METHODS
For the purposes of this review, we assessed study protocols that evaluate coronary vasomotor response as reported in the literature. We compared these protocols regarding a number of procedural aspects and chose six examples to highlight the differences and uniqueness.
RESULTS
Currently, numerous protocols co-exist and vary in vascular domains tested, the manner in which to test these domains (e.g., preprocedural discontinuation of medication, provocative agent, solution, infusion time, and target artery) and techniques used for measurements (e.g., Doppler vs thermodilution technique).
CONCLUSIONS
This lack of consensus on a uniform functional testing protocol hampers both a broader clinical acceptance of the concepts of coronary vasomotor dysfunction, and the widespread adoption of such testing protocols in current clinical practice. Furthermore, the endotype of coronary vasomotor dysfunction might differ among the few specialised centres that perform CFT as a result of the use of different protocols.
Topics: Angina Pectoris; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Heart; Humans; Vasomotor System
PubMed: 34278990
DOI: 10.4244/EIJ-D-21-00402 -
Cryobiology Dec 2022Vitrification can extend the banking life of articular cartilage (AC) and improve osteochondral transplantation success. Current vitrification protocols require...
Vitrification can extend the banking life of articular cartilage (AC) and improve osteochondral transplantation success. Current vitrification protocols require optimization to enable them to be implemented in clinical practice. Sucrose as a non-permeating cryoprotective agent (CPA) and clinical grade chondroitin sulfate (CS) and ascorbic acid (AA) as antioxidants were investigated for their ability to improve a current vitrification protocol for AC. The aim of this study was to assess the impact of sucrose and CS/AA supplementation on post-warming chondrocyte viability in vitrified AC. Porcine osteochondral dowels were randomly vitrified and warmed with one established protocol (Protocol 1) and seven modified protocols (Protocols 2-8) followed by chondrocyte viability assessment. Sucrose supplementation in both vitrification and warming media (Protocol 4) resulted in significantly higher (p = 0.018) post-warming chondrocyte viability compared to the protocol without sucrose (Protocol 1). There was no significant difference (p = 0.298) in terms of post-warming chondrocyte viability between sucrose-supplemented DMEM + CS solution (Protocol 4) and Unisol-CV (UCV) + CS (Protocol 6) solution. Clinical grade CS and AA contributed to similar post-warming chondrocyte viability to previous studies using research grade CS and AA, indicating their suitability for clinical use. The addition of an initial step (step 0) to reduce the initial concentration of CPAs to minimize osmotic effects did not enhance chondrocyte viability in the superficial layer of AC. In conclusion, sucrose-supplemented DMEM + clinical grade CS (Protocol 4) could be an ideal protocol to be investigated for future use in clinical applications involving vitrified AC.
Topics: Swine; Animals; Vitrification; Chondrocytes; Cartilage, Articular; Cryopreservation; Cryoprotective Agents; Sucrose; Ascorbic Acid; Chondroitin Sulfates; Dietary Supplements
PubMed: 36155184
DOI: 10.1016/j.cryobiol.2022.09.004 -
Clinical Advances in Hematology &... May 2021Single-agent lenalidomide has modest activity in diffuse large B-cell lymphoma (DLBCL) and is thought to be more potent in activated B-cell (ABC) lymphomas, which are... (Review)
Review
Single-agent lenalidomide has modest activity in diffuse large B-cell lymphoma (DLBCL) and is thought to be more potent in activated B-cell (ABC) lymphomas, which are more treatment-resistant. However, the addition of lenalidomide to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in randomized clinical trials has shown equivocal benefit, despite phase 2 studies that suggested otherwise. These equivocal results suggest that either the cell of origin (COO) has limited importance for prescribing lenalidomide, or that lenalidomide is not the optimal agent for exploiting the vulnerability of ABC lymphomas. As more recent analyses have shown that the genetic landscape of DLBCL is considerably more complex than the binary COO paradigm, the disappointing impact of lenalidomide is less surprising. In contrast to the marginal benefit from the addition of lenalidomide to R-CHOP, recent studies suggest that lenalidomide in combination with novel agents has potent activity. Lenalidomide was recently approved in combination with the anti-monoclonal B-cell antibody tafasitamab for patients with relapsed DLBCL after 1 to 3 previous treatments. This combination has led to surprisingly prolonged progression-free survival rates, along with possible cure in a subset of patients. In addition, early-phase single-arm trials are also showing deep and durable responses in relapsed patients when lenalidomide is combined with the novel agents ibrutinib and venetoclax. Although these drugs have limited single-agent activity in DLBCL, their pronounced activity in combination suggests a possible unique synergistic effect. Overall, recent studies suggest that lenalidomide will continue to be an active player in the treatment for DLBCL but likely in combination with other novel agents rather than in combination with chemotherapy.
Topics: Angiogenesis Inhibitors; Animals; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin; Humans; Immunologic Factors; Lenalidomide; Lymphoma, Large B-Cell, Diffuse; Prednisone; Rituximab; Treatment Outcome; Vincristine
PubMed: 33989279
DOI: No ID Found