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Diagnostic Pathology Jun 2024Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and...
BACKGROUND
Waldenström's macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) involving the bone marrow (BM) with presence of IgM monoclonal protein, and comprises > 95% of all LPL cases. Rituximab-based regimens have been predominant in the management of WM. Infusion-related reactions (IRRs) are a primary concern with rituximab, although it is generally better tolerated with less toxicity than conventional anticancer agents. Here, we present an autopsy case of an elderly man who died suddenly after receiving the initial infusion of rituximab for WM/LPL.
CASE PRESENTATION
An 84-year-old man was found dead in his bedroom. He had undergone the initial intravenous rituximab infusion for progressive anemia related to Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) approximately 15 h before death. Although the protocol for rituximab administration and additional medication was considered appropriate, he exhibited several symptoms consistent with infusion-related reactions (IRRs) during the infusion. Autopsy revealed monotonous proliferation of small-to-medium-sized lymphocytic cells in the bone marrow, consistent with the premortem diagnosis of WM/LPL. Additionally, immunoglobulin λ-light chain-derived amyloid (ALλ) deposition was identified in all organs other than the brain. Although ALλ deposition and LPL infiltration were found in the heart, they were not severe enough to cause severe functional impairment. Severe congestion and/or edema were observed in the lungs, liver, and brain. Although significant inflammatory cell infiltration was not found in any organs, laboratory tests revealed elevated serum levels of inflammatory cytokines, including interleukin-1β, interleukin-6, tumor necrosis factor-α and the presence of IgM-λ monoclonal protein.
CONCLUSION
Acute IRRs associated with the initial rituximab infusion were the major contributing factor to his sudden unexpected death. The autopsy findings of present case suggest the necessity for thorough monitoring of older patients with WM/LPL undergoing rituximab treatment, particularly when pronounced IRRs occur during the first administration, in addition to investigating complications of WM/LPL before infusion.
Topics: Humans; Waldenstrom Macroglobulinemia; Rituximab; Male; Aged, 80 and over; Autopsy; Death, Sudden; Antineoplastic Agents, Immunological; Bone Marrow; Fatal Outcome; Infusions, Intravenous
PubMed: 38943126
DOI: 10.1186/s13000-024-01519-9 -
BMC Infectious Diseases Jun 2024Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic...
BACKGROUND
Intravenous fosfomycin (IVFOF) is gaining interest in severe infections. Its use may be limited by adverse events (AEs). Little experience exists on IVFOF therapeutic drug monitoring (TDM) in real-life setting.
PATIENTS AND METHODS
Retrospective study of patients receiving IVFOF for > 48 h at Policlinico Hospital (Milan, Italy) from 01/01/2019 to 01/01/2023. AEs associated to IVFOF graded CTCAE ≥ II were considered. Demographic and clinical risk factors for IVFOF-related AEs were analysed with simple and multivariable regression models. The determination of IVFOF TDM was made by a rapid ultraperformance liquid chromatography mass spectrometry method (LC-MS/MS) on plasma samples. The performance of TDM (trough levels (Cmin) in intermittent infusion, steady state levels (Css) in continuous infusion) in predicting AEs ≤ 5 days after its assessment was evaluated.
RESULTS
Two hundred and twenty-four patients were included. At IVFOF initiation, 81/224 (36.2%) patients were in ICU and 35/224 (15.7%) had septic shock. The most frequent infection site was the low respiratory tract (124/224, 55.4%). Ninety-five patients (42.4%) experienced ≥ 1AEs, with median time of 4.0 (2.0-7.0) days from IVFOF initiation. Hypernatremia was the most frequent AE (53/224, 23.7%). Therapy discontinuation due to AEs occurred in 38/224 (17.0%). ICU setting, low respiratory tract infections and septic shock resulted associated with AEs (RR 1.59 (95%CI:1.09-2.31), 1.46 (95%CI:1.03-2.07) and 1.73 (95%CI:1.27-2.37), respectively), while IVFOF daily dose did not. Of the 68 patients undergone IVFOF TDM, TDM values predicted overall AEs and hypernatremia with AUROC of 0.65 (95%CI:0.44-0.86) and 0.91 (95%CI:0.79-1.0) respectively for Cmin, 0.67 (95%CI:0.39-0.95) and 0.76 (95%CI:0.52-1.0) respectively for Css.
CONCLUSIONS
We provided real world data on the use of IVFOF-based regimens and associated AEs. IVFOF TDM deserves further research as it may represent a valid tool to predict AEs.
KEY POINTS
Real world data on intravenous fosfomycin for severe bacterial infections. AEs occurred in over 40% (therapy discontinuation in 17%) and were related to baseline clinical severity but not to fosfomycin dose. TDM showed promising results in predicting AEs.
Topics: Humans; Fosfomycin; Female; Male; Retrospective Studies; Anti-Bacterial Agents; Middle Aged; Drug Monitoring; Risk Factors; Aged; Administration, Intravenous; Italy; Adult; Tandem Mass Spectrometry
PubMed: 38943088
DOI: 10.1186/s12879-024-09541-4 -
BMC Geriatrics Jun 2024Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Malnutrition of older individuals, leads to significant functional decline, reducing their quality of life. Lifestyle interventions; dietary improvements and supplementation are explored to enhance the physical function of older adults. The current study aimed to assess the impact of oral nutritional supplements (ONS) on the functional and activity levels of Sri Lankan older adults.
METHODS
This randomized controlled trial included; an intervention group (IG) receiving 200 mL of ONS providing 247 kcal per serving, for 12 weeks and a control group (CG) receiving an equivalent volume of water. Changes in handgrip strength, knee extension strength, gait speed, functional and activity levels were assessed.
RESULTS
The IG showed significant improvements in handgrip strength (43.96 ± 18.61 kg vs. 32.81 ± 17.92 kg; p < 0.001) and knee extension strength (23.45 ± 2.29 kg vs. 16.41 ± 2.09 kg; p < 0.001) following 12 weeks compared to the CG. The IG also exhibited significant improvements in gait speed (1.31 ± 0.52 m/s vs. 0.87 ± 0.26 m/s), Barthel index score, (0.30 ± 0.47 vs. -0.18 ± 0.66), PASE score (0.52 ± 17.79 vs. -1.60 ± 21.77) and IPAQ categories.
CONCLUSIONS
ONS was found to be effective in improving the functional and physical activity levels of malnourished older adults.
TRIAL REGISTRATION
Sri Lanka Clinical Trial Registry SLCTR/2022/021. Registered on 06/10/2022.
Topics: Humans; Male; Aged; Female; Dietary Supplements; Malnutrition; Exercise; Hand Strength; Sri Lanka; Walking Speed; Physical Functional Performance; Aged, 80 and over; Middle Aged; Administration, Oral
PubMed: 38943086
DOI: 10.1186/s12877-024-05164-1 -
Respiratory Care Jun 2024
Topics: Humans; Nebulizers and Vaporizers; Ventilators, Mechanical; Equipment Design; Administration, Inhalation; High-Frequency Jet Ventilation
PubMed: 38942599
DOI: 10.4187/respcare.12218 -
Progress in Molecular Biology and... 2024Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation,... (Review)
Review
Repurposing pharmaceuticals is a technique used to find new, alternate clinical applications for approved drug molecules. It may include altering the drug formulation, route of administration, dose or the dosage regimen. The process of repurposing medicines starts with screening libraries of previously approved drugs for the targeted disease condition. If after an the initial in silico, in vitro or in vivo experimentation, the molecule has been found to be active against a particular target, the molecule is considered as a good candidate for clinical trials. As the safety profile of such molecules is available from the previous data, significant time and resources are saved. These advantages of drug repurposing approach make it especially helpful for finding treatments for rapidly evolving conditions including bacterial infections. An ever-increasing incidence of antimicrobial resistance, owing to the mutations in bacterial genome, leads to therapeutic failure of many approved antibiotics. Repurposing the approved drug molecules for use as antibiotics can provide an effective means for the combating life-threatening bacterial diseases. A number of drugs have been considered for drug repurposing against bacterial infections. These include, but are not limited to, Auranofin, Closantel, and Toremifene that have been repurposed for various infections. In addition, the reallocation of route of administration, redefining dosage regimen and reformulation of dosage forms have also been carried out for repurposing purpose. The current chapter addresses the drug discovery and development process with relevance to repurposing against bacterial infections.
Topics: Drug Repositioning; Humans; Bacterial Infections; Animals; Anti-Bacterial Agents
PubMed: 38942533
DOI: 10.1016/bs.pmbts.2024.03.031 -
The European Respiratory Journal Jun 2024
Topics: Humans; Epoprostenol; Hypertension, Pulmonary; Pulmonary Disease, Chronic Obstructive; Administration, Inhalation; Antihypertensive Agents
PubMed: 38942439
DOI: 10.1183/13993003.E6306-2024 -
BMJ Open Quality Jun 2024Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous...
OBJECTIVES
Intravenous medication errors continue to significantly impact patient safety and outcomes. This study sought to clarify the complexity and risks of the intravenous administration process.
DESIGN
A qualitative focus group interview study.
SETTING
Focused interviews were conducted using process mapping with frontline nurses responsible for medication administration in September 2020.
PARTICIPANTS
Front line experiened nurses from a Japanese tertiary teaching hospital.
PRIMARY AND SECONDARY OUTCOME MEASURES
The primary outcome measure was to identify the mental models frontline nurses used during intravenous medication administration, which influence their interactions with patients, and secondarily, to examine the medication process gaps between the mental models nurses perceive and the actual defined medication administration process.
RESULTS
We found gaps between the perceived clinical administration process and the real process challenges with an emphasis on the importance of verifying to see if the drug was ordered for the patient immediately before its administration.
CONCLUSIONS
This novel and applied improvement approach can help nurses and managers better understand the process vulnerability of the infusion process and develop a deeper understanding of the administration steps useful for reliably improving the safety of intravenous medications.
Topics: Humans; Qualitative Research; Medication Errors; Focus Groups; Patient Safety; Infusions, Intravenous; Perception; Female; Administration, Intravenous; Adult; Nursing Staff, Hospital; Male; Japan; Interviews as Topic; Attitude of Health Personnel
PubMed: 38942437
DOI: 10.1136/bmjoq-2024-002809 -
Microbial Pathogenesis Jun 2024Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of...
Campylobacter jejuni is one of the major causes of bacterial gastrointestinal disease in humans worldwide. This foodborne pathogen colonizes the intestinal tracts of chickens, and consumption of chicken and poultry products is identified as a common route of transmission. We analyzed two C. jejuni strains after oral challenge with 10 CFU/ml of C. jejuni per chick; one strain was a robust colonizer (A74/C) and the other a poor colonizer (A74/O). We also found extensive phenotypic differences in growth rate, biofilm production, and in vitro adherence, invasion, intracellular survival, and transcytosis. Strains A74/C and A74/O were genotypically similar with respect to their whole genome alignment, core genome, and ribosomal MLST, MLST, flaA, porA, and PFGE typing. The global proteomes of the two congenic strains were quantitatively analyzed by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) and 618 and 453 proteins were identified from A74/C and A74/O isolates, respectively. Cluster of Orthologous Groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that carbon metabolism and motility proteins were distinctively overexpressed in strain A74/C. The robust colonizer also exhibited a unique proteome profile characterized by significantly increased expression of proteins linked to adhesion, invasion, chemotaxis, energy, protein synthesis, heat shock proteins, iron regulation, two-component regulatory systems, and multidrug efflux pump. Our study underlines phenotypic, genotypic, and proteomic variations of the poor and robust colonizing C. jejuni strains, suggesting that several factors may contribute to mediating the different colonization potentials of the isogenic isolates.
PubMed: 38942248
DOI: 10.1016/j.micpath.2024.106766 -
Annual Review of Food Science and... Jun 2024Because the feeding of our body through the oral route can be associated with many drawbacks due to the degradation of natural molecules during transit in the... (Review)
Review
Because the feeding of our body through the oral route can be associated with many drawbacks due to the degradation of natural molecules during transit in the gastrointestinal tract, a transdermal delivery strategy, usually employed in the pharmaceutical field, can present an effective alternative for delivery of bioactives and nutrients from foods. In this review, the chance to feed the body with nutritive and bioactive molecules from food through transdermal administration is discussed. Various nanotechnological devices employed for topical and transdermal delivery of bioactive compounds are described. In addition, mechanisms underlying their potential use in the delivery of nutritive molecules, as well as their capability to efficaciously reach the dermis and promote systemic distribution, are detailed.
Topics: Humans; Administration, Cutaneous; Animals; Skin; Drug Delivery Systems; Skin Absorption
PubMed: 38941493
DOI: 10.1146/annurev-food-072023-034528 -
Science Advances Jun 2024Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate...
Oral medication for ulcerative colitis (UC) is often hindered by challenges such as inadequate accumulation, limited penetration of mucus barriers, and the intricate task of mitigating excessive ROS and inflammatory cytokines. Here, we present a strategy involving sodium alginate microspheres (SAMs) incorporating M2 macrophage membrane (M2M)-coated Janus nanomotors (denominated as Motor@M2M) for targeted treatment of UC. SAM provides a protective barrier, ensuring that Motor@M2M withstands the harsh gastric milieu and exhibits controlled release. M2M enhances the targeting precision of nanomotors to inflammatory tissues and acts as a decoy for the neutralization of inflammatory cytokines. Catalytic decomposition of HO by MnO in the oxidative microenvironment generates O bubbles, propelling Motor@M2M across the mucus barrier into inflamed colon tissues. Upon oral administration, Motor@M2M@SAM notably ameliorated UC severity, including inflammation mitigation, ROS scavenging, macrophage reprogramming, and restoration of the intestinal barrier and microbiota. Consequently, our investigation introduces a promising oral microsphere formulation of macrophage-biomimetic nanorobots, providing a promising approach for UC treatment.
Topics: Colitis, Ulcerative; Microspheres; Macrophages; Animals; Administration, Oral; Mice; Alginates; Humans; Disease Models, Animal; Reactive Oxygen Species; Nanoparticles; Drug Delivery Systems; Hydrogen Peroxide
PubMed: 38941458
DOI: 10.1126/sciadv.ado6798