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Advanced Functional Materials Jun 2019Combination chemotherapy administering multiple chemo-agents is widely exploited for the treatment of various cancers in the clinic. Specially for hepatocellular...
Combination chemotherapy administering multiple chemo-agents is widely exploited for the treatment of various cancers in the clinic. Specially for hepatocellular carcinoma (HCC), one of the most common malignancies, a co-administration of combinational cytostatic multi-kinase inhibitors and cytotoxic chemo-agents has been suggested as a potential curative approach. Here, Janus microcarriers were developed for the controlled local combination chemotherapy of HCC. The Janus microcarriers are composed of polycaprolactone (PCL) compartment and magnetic nanoparticles-loaded poly(lactide-co-glycolic acid) (PLGA) compartment which contain hydrophobic regorafenib and hydrophilic doxorubicin, respectively. Exploiting the magnetic anisotropy, rotational motion of the Janus microcarriers is controlled with magnetic field, which enables the active co-release of dual chemo-agents. Furthermore, Janus microcarriers exhibit magnetic resonance (MR) contrast effect, supporting the successful transcatheter intra-arterial delivery of the combination chemo-agents loaded the microcarriers to the targeted tumor. This Janus microcarriers potentially serve as a general combinational chemo-therapeutic platform for the co-delivery of various combinations of multi-chemo-agents.
PubMed: 38957778
DOI: 10.1002/adfm.201901384 -
Open Forum Infectious Diseases Jul 2024We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment...
We evaluated use of maribavir (MBV) for treatment of 15 episodes of refractory/resistant cytomegalovirus infection in 13 solid organ transplant recipients. Treatment failure due to treatment-emergent MBV resistance or early virological recurrence after MBV discontinuation occurred in 7 (47%) episodes. Sustained viral clearance was achieved in 6 (40%) episodes.
PubMed: 38957689
DOI: 10.1093/ofid/ofae335 -
Ghana Medical Journal Sep 2023The study objective was to evaluate the prescription pattern and use of anti-seizure medications (ASMs) in patients with a seizure disorder and to evaluate if a change...
OBJECTIVE
The study objective was to evaluate the prescription pattern and use of anti-seizure medications (ASMs) in patients with a seizure disorder and to evaluate if a change in the ASM dose had a beneficial effect on seizure control, observed through Therapeutic Drug Monitoring [TDM] level of ASMs.
METHODS
Details of anti-seizure medications with their therapeutic levels in the blood of patients with seizure disorder were analysed.
DESIGN
Hospital-based retrospective analysis of patient case records.
SETTINGS
Therapeutic Drug Monitoring OPD of a tertiary care public teaching hospital.
PARTICIPANTS
Case records of 918 patients with seizure disorder from 2016-2021.
RESULTS
Data of men (53%) and women (47%) aged between 18-75 years was assessed About 62% (566/918) of patients were on levetiracetam, the most frequently prescribed anti-seizure medication. Whenever the ASMs dose was increased or decreased based on TDM levels, it was associated with a significant increase in the frequency of break-through seizures [OR- 5 (95% CI: 1.28-19.46)]. However, significant seizure control was observed when the patients were on the same maintenance dose of the anti-seizure medication [OR- 0.2 (95% CI: 0.06-0.63)]. Whenever an additional new anti-epileptic drug was prescribed or removed from the pre-existing anti-epileptic medications, it did not significantly impact seizure control.
CONCLUSION
Individualising drug therapy and therapeutic drug monitoring for each patient, along with patient factors such as medication compliance, concomitant drug and disease history, and pharmacogenetic assessment, should be the ideal practice in patients with seizures for better seizure control.
FUNDING
None declared.
Topics: Humans; Anticonvulsants; Male; Female; Middle Aged; Adult; Retrospective Studies; Aged; Adolescent; Drug Monitoring; Young Adult; Levetiracetam; Seizures; Tertiary Care Centers; Practice Patterns, Physicians'; Hospitals, Public; Epilepsy
PubMed: 38957674
DOI: 10.4314/gmj.v57i3.5 -
Oxidative Medicine and Cellular... 2024Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and...
Myocardial infarction (MI) is irreversible damage to the myocardial tissue caused by prolonged ischemia/hypoxia, subsequently leading to loss of contractile function and myocardial damage. However, after a perilous period, ischemia-reperfusion (IR) itself causes the generation of oxygen free radicals, disturbance in cation homeostasis, depletion of cellular energy stores, and activation of innate and adaptive immune responses. The present study employed Abatacept (ABT), which is an anti-inflammatory drug, originally used as an antirheumatic response agent. To investigate the cardioprotective potential of ABT, primarily, the dose was optimized in a chemically induced model of myocardial necrosis. Thereafter, ABT optimized the dose of 5 mg/kg s.c. OD was investigated for its cardioprotective potential in a surgical model of myocardial IR injury, where animals ( = 30) were randomized into five groups: Sham, IR-C, Telmi10 + IR (Telmisartan, 10 mg/kg oral OD), ABT5 + IR, ABT . ABT and telmisartan were administered for 21 days. On the 21st day, animals were subjected to LAD coronary artery occlusion for 60 min, followed by reperfusion for 45 min. Further, the cardioprotective potential was assessed through hemodynamic parameters, oxidant-antioxidant biochemical enzymatic parameters, cardiac injury, inflammatory markers, histopathological analysis, TUNEL assay, and immunohistochemical evaluation, followed by immunoblotting to explore signaling pathways. The statistics were performed by one-way analysis of variance, followed by the Tukey comparison post hoc tests. Noteworthy, 21 days of ABT pretreatment amended the hemodynamic and ventricular functions in the rat models of MI. The cardioprotective potential of ABT is accompanied by inhibiting MAP kinase signaling and modulating Nrf-2/HO-1 proteins downstream signaling cascade. Overall, the present work bolsters the previously known anti-inflammatory role of ABT in MI and contributes a mechanistic insight and application of clinically approved drugs in averting the activation of inflammatory response.
Topics: Animals; Rats; Myocardial Infarction; Disease Models, Animal; Male; Inflammation; Abatacept; Rats, Wistar; Myocardial Reperfusion Injury
PubMed: 38957586
DOI: 10.1155/2024/3534104 -
MedEdPORTAL : the Journal of Teaching... 2024Medication errors can lead to significant adverse events. Nearly 50% of medication errors occur during the prescription-writing stage of the medication use process, and...
INTRODUCTION
Medication errors can lead to significant adverse events. Nearly 50% of medication errors occur during the prescription-writing stage of the medication use process, and effective interprofessional collaboration and communication are key to reducing error in this process.
METHODS
We developed a three-part, 60-minute, interprofessional education activity providing medical, physician assistant, and pharmacy students the opportunity to practice collegial interprofessional communication surrounding prescribing practices. Learners met virtually initially as a large group and divided into small groups facilitated by a health professional. Part 1 involved reviewing two prescriptions prepared by learners; part 2 was a discussion about the education, roles, and responsibilities of each profession; and part 3 focused on identifying prescription errors in examples provided by faculty. Students completed a post-pre survey measuring their perception of learning the Interprofessional Collaborative Competency Attainment Survey (ICCAS) areas.
RESULTS
Of 317 participants (151 doctor of osteopathy, 68 master of physician assistant studies, and 98 doctor of pharmacy students), 286 completed the post-pre survey, for a 90% response rate. Students reported statistically significant ( < .001) increases in all 20 questions spanning the six ICCAS areas.
DISCUSSION
The virtual format allowed multiple institutions to participate from various locations. It broadened the learners' experience by fostering interaction among those with varied perspectives and allowed collaboration between locations and programs that otherwise could not have participated. The activity introduced students to virtual collaboration and key telehealth skills, enhancing their confidence and familiarity with virtual interactions in a professional setting.
Topics: Humans; Physician Assistants; Surveys and Questionnaires; Interprofessional Relations; Cooperative Behavior; Interprofessional Education; Medication Errors; Students, Pharmacy; Clinical Competence; Education, Pharmacy; Osteopathic Medicine; Drug Prescriptions
PubMed: 38957535
DOI: 10.15766/mep_2374-8265.11403 -
Oncoimmunology 2024Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of have been associated with a positive response to ICI in multiple cancer types....
Gut microbiota impacts responses to immune checkpoint inhibitors (ICI). A high level of have been associated with a positive response to ICI in multiple cancer types. Here, based on fecal shotgun metagenomics data, we show in two independent cohorts of patients with non-small cell lung cancer and advanced melanoma that a high level of at baseline is positively associated with a better clinical response to ICI. In MCA205 tumor-bearing mice, administration of strain EXL01, already in clinical development for Inflammatory Bowel Disease, restores the anti-tumor response to ICI in the context of antibiotic-induced microbiota perturbation at clinical and tumor transcriptomics level. In vitro, EXL01 strain enhances T cell activation in the presence of ICI. Interestingly, oral administration of EXL01 strain did not induce any change in fecal microbiota diversity or composition, suggesting a direct effect on immune cells in the small intestine. strain EXL01 will be evaluated as an adjuvant to ICI in multiple cancers in the near future.
Topics: Immune Checkpoint Inhibitors; Animals; Humans; Mice; Gastrointestinal Microbiome; Faecalibacterium prausnitzii; Female; Carcinoma, Non-Small-Cell Lung; Melanoma; Feces; Male; Lung Neoplasms; Cell Line, Tumor; Mice, Inbred C57BL
PubMed: 38957477
DOI: 10.1080/2162402X.2024.2374954 -
Frontiers in Immunology 2024Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune...
BACKGROUND
Bone metastases (BoMs) are prevalent in patients with metastatic non-small-cell lung cancer (NSCLC) however, there are limited data detailing how BoMs respond to immune checkpoint inhibitors (ICIs). The purpose of this study was to compare the imaging response to ICIs of BoMs against visceral metastases and to evaluate the effect of BoMs on survival.
MATERIALS AND METHODS
A retrospective, multicentre cohort study was conducted in patients with NSCLC treated with nivolumab or pembrolizumab in Alberta, Canada from 2015 to 2020. The primary endpoint was the real-world organ specific progression free survival (osPFS) of bone versus visceral metastases. Visceral metastases were categorized as adrenal, brain, liver, lung, lymph node, or other intra-abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs.
RESULTS
A total of 573 patients were included of which all patients had visceral metastases and 243 patients (42.4%) had BoMs. High PD-L1 expression was identified in 268 patients (46.8%). No significant difference in osPFS was observed between bone, liver, and intra-abdominal metastases (p=0.20 and p=0.76, respectively), with all showing shorter osPFS than other disease sites. There was no difference in the osPFS of extra-thoracic sites of disease in patients with high PD-L1 expression. There was significant discordance between visceral disease response and bone disease response to ICI (p=0.047). The presence of BoMs was an independent poor prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01).
CONCLUSION
Metastatic bone, liver, and intra-abdominal lesions demonstrated inferior clinical responses to ICI relative to other sites of disease. Additionally, the presence of bone and liver metastases were independent poor prognostic factors for overall survival. This real-world data suggests that BoMs respond poorly to ICI and may require treatment adjuncts for disease control.
Topics: Humans; Immune Checkpoint Inhibitors; Male; Female; Carcinoma, Non-Small-Cell Lung; Aged; Retrospective Studies; Lung Neoplasms; Middle Aged; Bone Neoplasms; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Adult; Treatment Outcome
PubMed: 38957472
DOI: 10.3389/fimmu.2024.1379056 -
Frontiers in Immunology 2024Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy...
INTRODUCTION
Chemoresistance constitutes a prevalent factor that significantly impacts thesurvival of patients undergoing treatment for smal-cell lung cancer (SCLC). Chemotherapy resistance in SCLC patients is generally classified as primary or acquired resistance, each governedby distinct mechanisms that remain inadequately researched.
METHODS
In this study, we performed transcriptome screening of peripheral blood plasma obtainedfrom 17 patients before and after receiving combined etoposide and platinum treatment. We firs testimated pseudo-single-cell analysis using xCell and ESTIMATE and identified differentially expressed genes (DEGs), then performed network analysis to discover key hub genes involved in chemotherapy resistance.
RESULTS
Our analysis showed a significant increase in class-switched memory B cell scores acrossboth chemotherapy resistance patterns, indicating their potential crucial role in mediatingresistance. Moreover, network analysis identifed , , and as potential contributors to primary resistance, with , and emerging assignificant factors in acquired resistance, providing valuable insights into chemotherapy resistancein SCLC.
DISCUSSION
These findings offer valuable insights for understanding chemotherapy resistance and related gene signatures in SCLC, which could help further biological validation studies.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Drug Resistance, Neoplasm; Biomarkers, Tumor; Transcriptome; Female; Male; Gene Expression Profiling; Middle Aged; Gene Expression Regulation, Neoplastic; Aged; Antineoplastic Combined Chemotherapy Protocols; Etoposide
PubMed: 38957470
DOI: 10.3389/fimmu.2024.1338162 -
Frontiers in Immunology 2024Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in...
Targeted therapy and immunotherapy are both important in the treatment of non-small-cell lung cancer (NSCLC). Accurate diagnose and precise treatment are key in achieving long survival of patients. fusion is a rare oncogenic factor, whose optimal detection and treatment are not well established. Here, we report on a 32-year-old female lung adenocarcinoma patient with positive PD-L1 and negative driver gene detected by DNA-based next-generation sequencing (NGS). A radical resection of the primary lesion after chemotherapy combined with PD-1 checkpoint inhibitor administration indicated primary immuno-resistance according to her pathological response and rapid relapse. A rare was detected by RNA-based NGS, which was confirmed by fluorescence hybridization. Multiplex immunofluorescence revealed a PD-L1 related heterogeneous immunosuppressive microenvironment with little distribution of CD4+ T cells and CD8+ T cells. Savolitinib therapy resulted in a progression-free survival (PFS) of >12 months, until a new secondary resistance mutation in p.D1228H was detected by re-biopsy and joint DNA-RNA-based NGS after disease progression. In this case, fusion NSCLC was primarily resistant to immunotherapy, sensitive to savolitinib, and developed secondary p.D1228H mutation after targeted treatment. DNA-RNA-based NGS is useful in the detection of such molecular events and tracking of secondary mutations in drug resistance. To this end, DNA-RNA-based NGS may be of better value in guiding precise diagnosis and individualized treatment in this patient population.
Topics: Humans; Female; Adenocarcinoma of Lung; Adult; Lung Neoplasms; High-Throughput Nucleotide Sequencing; Proto-Oncogene Proteins c-met; Oncogene Proteins, Fusion; Drug Resistance, Neoplasm; Immune Checkpoint Inhibitors
PubMed: 38957460
DOI: 10.3389/fimmu.2024.1386561 -
Frontiers in Endocrinology 2024From the introduction of continuous glucose monitoring (CGM) in treatments of type 1 diabetes, particularly its integration with insulin pumps, there has been a quest...
Glycemic variability through the perspective of the glycemia risk index and time in range and their association with glycated hemoglobin A1c in pediatric patients on sensor-augmented pump therapy.
INTRODUCTION
From the introduction of continuous glucose monitoring (CGM) in treatments of type 1 diabetes, particularly its integration with insulin pumps, there has been a quest for new parameters that describe optimal glycemic control. As of the consensus reached in 2019, the ambulatory glucose profile (AGP) has become the standard, with time in range (TIR) emerging as a fundamental parameter for metabolic control assessment. However, with technological advancements, new parameters, such as the glycemia risk index (GRI), have been introduced and clinically utilized. Therefore, exploring the relationships between traditional and novel parameters to understand metabolic control comprehensively is imperative.
MATERIALS AND METHODS
This study was conducted at the Pediatric Clinic of the University Hospital of the Republic of Srpska Banja Luka between January and July 2023. The participants were randomly selected, with the inclusion criteria specifying an age greater than eight years and a diabetes type 1 duration exceeding two years. All participants were required to use a sensor-augmented insulin pump for the next three months (90 days), irrespective of prior use, with the suspend-before-low option activated.
RESULTS
Of the 35 participants, 30 completed the study, 14 (46.7%) of whom were male. The mean age of the subjects was 14.90 ± 2.88 years, and the mean duration of diabetes was 7.83 ± 4.76 years. Over the 90-day period, HbA1c increased to an average of 7.31%. The analysis revealed significant effects of TIR (β=-0.771) and GRI (β=0.651) on HbA1c. Furthermore, GRI and TIR strongly correlated (β=-0.953).
DISCUSSION AND CONCLUSION
New parameters generated from the ambulatory glucose profile (AGP) can help clinicians create a complete picture of a patient's metabolic control in relation to HbA1c levels. Additionally, the GRI is a mathematically tailored parameter that incorporates all components of the ambulatory glucose profile and demonstrates strong correlations with laboratory-measured HbA1c and TIR. The GRI potentially can become a valuable statistical parameter for evaluating and managing patients in routine clinical practice.
Topics: Humans; Glycated Hemoglobin; Insulin Infusion Systems; Male; Diabetes Mellitus, Type 1; Female; Child; Blood Glucose; Adolescent; Blood Glucose Self-Monitoring; Insulin; Hypoglycemic Agents; Glycemic Control
PubMed: 38957442
DOI: 10.3389/fendo.2024.1388245