-
Journal of the American Animal Hospital... May 2024Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here,...
Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.
Topics: Animals; Cats; Filgrastim; Cat Diseases; Azathioprine; Neutropenia; Medication Errors; Immunosuppressive Agents; Male; Methimazole; Female
PubMed: 38662994
DOI: 10.5326/JAAHA-MS-7409 -
BMC Chemistry Apr 20246-mercaptopurine (6-MP) is a chemotherapy drug mainly used to treat leukemia. It is a persistent organic pollutant and can remain in the environment for a long period of...
BACKGROUND
6-mercaptopurine (6-MP) is a chemotherapy drug mainly used to treat leukemia. It is a persistent organic pollutant and can remain in the environment for a long period of time. The presence of 6-MP in the environment poses a number of hazards and needs to be assessed to monitor its potential risk to human health and the environment. However, due to its trace amount in complicated matrices, a clean-up and preconcentration step before its determination is compulsory.
RESULTS
As a highly efficient adsorbent for the extrication of 6-mercaptopurine (6-MP), a novel carbon nanotube doped with camphor: decanoic acid deep eutectic solvent was synthesized and applied as a packing material for the pipette-tip micro solid phase extraction sorbent of 6-MP from tap, wastewater and seawater samples before its spectrophotometric determination. Characteristics and structure of this adsorbent was fully investigated. Factors affecting extraction, including type and volume of the eluent, ionic strength and pH of the sample solution, amount of adsorbent, and number of extraction and elution cycles were optimized using one-factor-at-a-time and response surface methodologies. The method was found to be linear in the range of 1 to 1000 µg/L with a limit of detection and quantification of 0.2 and 0.7 µg/L, respectively. Reproducibility as relative standard deviation was better than 4.6%.
CONCLUSION
Application of deep eutectic solvent modified carbon nanotube indicated suitable microextraction results and good potential for rapid extraction of trace amounts of 6-MP from different aqueous samples. The amount of sample required for the analysis was less than 10 mL and only 1.5 mg of the adsorbent was used. The total analysis time, including extraction was less than 15 min and the adsorbent could be used for at least 10 times, without significantly losing its adsorption ability. Compared to using unmodified usual carbon nanotubes, deep eutectic solvent doped carbon nanotubes showed 19.8% higher extraction ability.
PubMed: 38654336
DOI: 10.1186/s13065-024-01199-y -
Alimentary Pharmacology & Therapeutics Jun 2024Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied... (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
BACKGROUND
Data on cost-effectiveness of first-line infliximab in paediatric patients with Crohn's disease are limited. Since biologics are increasingly prescribed and accompanied by high costs, this knowledge gap needs to be addressed.
AIM
To investigate the cost-effectiveness of first-line infliximab compared to conventional treatment in children with moderate-to-severe Crohn's disease.
METHODS
We included patients from the Top-down Infliximab Study in Kids with Crohn's disease randomised controlled trial. Children with newly diagnosed moderate-to-severe Crohn's disease were treated with azathioprine maintenance and either five induction infliximab (biosimilar) infusions or conventional induction treatment (exclusive enteral nutrition or corticosteroids). Direct healthcare consumption and costs were obtained per patient until week 104. This included data on outpatient hospital visits, hospital admissions, drug costs, endoscopies and surgeries. The primary health outcome was the odds ratio of being in clinical remission (weighted paediatric Crohn's disease activity index<12.5) during 104 weeks.
RESULTS
We included 89 patients (44 in the first-line infliximab group and 45 in the conventional treatment group). Mean direct healthcare costs per patient were €36,784 for first-line infliximab treatment and €36,874 for conventional treatment over 2 years (p = 0.981). The odds ratio of first-line infliximab versus conventional treatment to be in clinical remission over 104 weeks was 1.56 (95%CI 1.03-2.35, p = 0.036).
CONCLUSIONS
First-line infliximab treatment resulted in higher odds of being in clinical remission without being more expensive, making it the dominant strategy over conventional treatment in the first 2 years after diagnosis in children with moderate-to-severe Crohn's disease.
TRIAL REGISTRATION NUMBER
NCT02517684.
Topics: Humans; Crohn Disease; Infliximab; Cost-Benefit Analysis; Male; Female; Child; Adolescent; Gastrointestinal Agents; Biosimilar Pharmaceuticals; Treatment Outcome; Azathioprine; Immunosuppressive Agents; Adrenal Cortex Hormones; Health Care Costs
PubMed: 38644588
DOI: 10.1111/apt.18000 -
Neuromuscular Disorders : NMD May 2024Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as...
Azathioprine is recommended as the first-line steroid-sparing immunosuppressive agent for myasthenia gravis. Mycophenolate and methotrexate are often considered as second-line choices despite widespread consensus on their efficacy. We aimed to gather real-world data comparing the tolerability and reasons for discontinuation for these agents, by performing a national United Kingdom survey of side effects and reasons for discontinuation of immunosuppressants in myasthenia gravis. Of 235 patients, 166 had taken azathioprine, 102 mycophenolate, and 40 methotrexate. The most common side effects for each agent were liver dysfunction for azathioprine (23 %), diarrhoea for mycophenolate (14 %), and fatigue for methotrexate (18 %). Women were generally more likely to experience side effects of immunosuppressants. Azathioprine was significantly more likely to be discontinued than mycophenolate and methotrexate due to side effects. There was no significant difference in treatment cessation due to lack of efficacy. This study highlights the significant side-effect burden of treatment for myasthenia gravis. Mechanisms to reduce azathioprine toxicity should be utilised, however mycophenolate and methotrexate appear to be good treatment choices if teratogenicity is not a concern. Women are disadvantaged due to higher frequency of side effects and considerations around pregnancy and breastfeeding. Treatments with improved tolerability are needed.
Topics: Humans; Myasthenia Gravis; Methotrexate; Female; Mycophenolic Acid; Azathioprine; Immunosuppressive Agents; Male; Middle Aged; Adult; Aged; United Kingdom
PubMed: 38626662
DOI: 10.1016/j.nmd.2024.03.010 -
World Journal of Gastroenterology Mar 2024Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines. Dose optimization guided by nudix hydrolase 15 () has significantly reduced the... (Clinical Trial)
Clinical Trial
BACKGROUND
Thiopurine-induced leucopenia significantly hinders the wide application of thiopurines. Dose optimization guided by nudix hydrolase 15 () has significantly reduced the early leucopenia rate, but there are no definitive biomarkers for late risk leucopenia prediction.
AIM
To determine the predictive value of early monitoring of DNA-thioguanine (DNATG) or 6-thioguanine nucleotides (6TGN) for late leucopenia under a -guided thiopurine dosing strategy in patients with Crohn's disease (CD).
METHODS
Blood samples were collected within two months after thiopurine initiation for detection of metabolite concentrations. Late leucopenia was defined as a leukocyte count < 3.5 × 10/L over two months.
RESULTS
Of 148 patients studied, late leucopenia was observed in 15.6% (17/109) of thiopurine methyltransferase () normal and 64.1% (25/39) of intermediate metabolizers. In patients suffering late leucopenia, early DNATG levels were significantly higher than in those who did not develop late leucopenia ( = 4.9 × 10). The DNATG threshold of 319.43 fmol/μg DNA could predict late leucopenia in the entire sample with an area under the curve (AUC) of 0.855 (sensitivity 83%, specificity 81%), and in normal metabolizers, the predictive performance of a threshold of 315.72 fmol/μg DNA was much more remarkable with an AUC of 0.902 (sensitivity 88%, specificity 85%). 6TGN had a relatively poor correlation with late leucopenia whether in the entire sample ( = 0.021) or / normal or intermediate metabolizers ( = 0.018, = 0.55, respectively).
CONCLUSION
Proactive therapeutic drug monitoring of DNATG could be an effective strategy to prevent late leucopenia in both / normal and intermediate metabolizers with CD, especially the former.
Topics: Humans; Crohn Disease; DNA; Leukopenia; Methyltransferases; Purines; Sulfhydryl Compounds; Thioguanine
PubMed: 38617736
DOI: 10.3748/wjg.v30.i12.1751 -
Acta Biomaterialia May 2024Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents,...
Photothermal therapy (PTT) holds great promise as a cancer treatment modality by generating localized heat at the tumor site. Among various photothermal agents, gallium-based liquid metal (LM) has been widely used as a new photothermal-inducible metallic compound due to its structural transformability. To overcome limitations of random aggregation and dissipation of administrated LM particles into a human body, we developed LM-containing injectable composite hydrogel platforms capable of achieving spatiotemporal PTT and chemotherapy. Eutectic gallium-indium LM particles were first stabilized with 1,2-Distearoyl-sn‑glycero-3-phosphoethanolamine (DSPE) lipids. They were then incorporated into an interpenetrating hydrogel network composed of thiolated gelatin conjugated with 6-mercaptopurine (MP) chemodrug and poly(ethylene glycol)-diacrylate. The resulted composite hydrogel exhibited sufficient capability to induce MDA-MB-231 breast cancer cell death through a multi-step mechanism: (1) hyperthermic cancer cell death due to temperature elevation by near-infrared laser irradiation via LM particles, (2) leakage of glutathione (GSH) and cleavage of disulfide bonds due to destruction of cancer cells. As a consequence, additional chemotherapy was facilitated by GSH, leading to accelerated release of MP within the tumor microenvironment. The effectiveness of our composite hydrogel system was evaluated both in vitro and in vivo, demonstrating significant tumor suppression and killing. These results demonstrate the potential of this injectable composite hydrogel for spatiotemporal cancer treatment. In conclusion, integration of PTT and chemotherapy within our hydrogel platform offers enhanced therapeutic efficacy, suggesting promising prospects for future clinical applications. STATEMENT OF SIGNIFICANCE: Our research pioneers a breakthrough in cancer treatments by developing an injectable hydrogel platform incorporating liquid metal (LM) particle-mediated photothermal therapy and 6-mercaptopurine (MP)-based chemotherapy. The combination of gallium-based LM and MP achieves synergistic anticancer effects, and our injectable composite hydrogel acts as a localized reservoir for specific delivery of both therapeutic agents. This platform induces a multi-step anticancer mechanism, combining NIR-mediated hyperthermic tumor death and drug release triggered by released glutathione from damaged cancer populations. The synergistic efficacy validated in vitro and in vivo studies highlights significant tumor suppression. This injectable composite hydrogel with synergistic therapeutic efficacy holds immense promise for biomaterial-mediated spatiotemporal treatment of solid tumors, offering a potent targeted therapy for triple negative breast cancers.
Topics: Hydrogels; Gallium; Humans; Female; Breast Neoplasms; Animals; Cell Line, Tumor; Injections; Phototherapy; Mice, Nude; Mice; Photothermal Therapy; Mice, Inbred BALB C
PubMed: 38604467
DOI: 10.1016/j.actbio.2024.04.011 -
Talanta Jul 20246-mercaptopurine (6-MP) as the effective anti-cancer drug was used for the treatment of Crohn's disease and acute lymphoblastic leukaemia, but the response to...
6-mercaptopurine (6-MP) as the effective anti-cancer drug was used for the treatment of Crohn's disease and acute lymphoblastic leukaemia, but the response to maintenance therapy was variable with individual differences. In order to control the dosage and decrease the side effects of 6-MP, a sensitive and stable assay was urgently needed for 6-MP monitoring. Herein, RuZn NPs with electrochemical oxidation property and oxidase-like activity was proposed for dual-mode 6-MP monitoring. Burr-like RuZn NPs were prepared and explored to not only exhibit an electrochemical oxidation signal at 0.78 V, but also displayed excellent oxidase-like performances. RuZn NPs were utilized for the dual-mode monitoring of 6-MP, attributing to the formation of Ru-SH covalent bonding. The colorimetric method showed good linearity from 10 μM to 5 mM with the limit of detection (LOD) of 300 nM, while the electrochemical method provided a higher sensitivity with the LOD of 37 nM in range from 100 nM to 200 μM. This work provided a new way for the fabrication of dual-functional nanotags with electroactivity and oxidase-like property, and opened a dual-mode approach for the 6-MP detection applications with complementary and satisfactory results.
Topics: Ruthenium Compounds; Zinc Compounds; Electrons; Oxidation-Reduction; Metal Nanoparticles; Antineoplastic Agents
PubMed: 38604042
DOI: 10.1016/j.talanta.2024.126075 -
Lupus Jun 2024Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women...
BACKGROUND
Pregnancy in women with systemic lupus erythematosus (SLE) has remained a great challenge for clinicians in terms of maternal and fetal outcomes. The outcomes in women with pre-existing lupus nephritis (LN) are variable. The impact of different classes of LN on maternal and fetal outcomes during pregnancy is not well defined, as data is very scarce, especially from the developing countries.
METHODS
A retrospective analysis was conducted on 52 women with 89 pregnancies. All had biopsy-proven LN. Those women who conceived at least 6 months after the diagnosis were included. The analysis was conducted between July 1998 and June 2018 at Sindh Institute of Urology and Transplantation (SIUT), evaluating the outcomes for both the mother and the fetus with a minimum follow-up of 12 months after child birth.
RESULTS
The mean maternal age at SLE diagnosis was 21.45 ± 6 years and at first pregnancy was 26.49 ± 5.63 years. The mean disease duration was 14.02 ± 19.8 months. At conception, 47 (52.8%) women were hypertensive, 9 (10%) had active disease while 38 (42.7%) and 42 (47.2%) were in complete and partial remission, respectively. A total of 17 (19.1%) were on mycophenolate mofetil (MMF), which was switched to azathioprine (AZA). Out of 89 pregnancies, 56 (62.9%) were successful, while 33 (37.07%) had fetal complications like spontaneous abortion, stillbirth, perinatal death, and intrauterine growth retardation (IUGR). There were more vaginal deliveries (33 [58.92%]) than caesarean sections (23 [41.07%]). Renal flare was observed in 33 (37.1%) women while 15 (16.9%) developed pre-eclampsia. Proliferative LN was found in 56 (62.9%) cases, but no significant differences were found in maternal and fetal outcomes in relation to LN classes ( = .58). However, disease outcomes at 12 months were significantly poor in those with active disease at the time of conception ( < .05). There was only one maternal death. A total of 10 (11.2%) women showed deterioration in renal function and 5 (5.6%) were dialysis-dependent at 12 months.
CONCLUSION
The maternal and fetal outcomes in pre-existing LN depend on the disease activity at the time of conception. No correlation was found between International Society of Nephrology/Renal Pathology Society (ISN/RPS) classes of LN and adverse disease and pregnancy outcomes.
Topics: Humans; Female; Pregnancy; Lupus Nephritis; Adult; Retrospective Studies; Pakistan; Pregnancy Complications; Pregnancy Outcome; Young Adult; Developing Countries; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Azathioprine; Mycophenolic Acid; Adolescent; Infant, Newborn
PubMed: 38594605
DOI: 10.1177/09612033241246642 -
Journal of Gastroenterology Jun 2024This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world...
BACKGROUND
This study evaluated the effectiveness of NUDT15 codon 139 genotyping in optimizing thiopurine treatment for inflammatory bowel disease (IBD) in Japan, using real-world data, and aimed to establish genotype-based treatment strategies.
METHODS
A retrospective analysis of 4628 IBD patients who underwent NUDT15 codon 139 genotyping was conducted. This study assessed the purpose of the genotyping test and subsequent prescriptions following the obtained results. Outcomes were compared between the Genotyping group (thiopurine with genotyping test) and Non-genotyping group (thiopurine without genotyping test). Risk factors for adverse events (AEs) were analyzed by genotype and prior genotyping status.
RESULTS
Genotyping test for medical purposes showed no significant difference in thiopurine induction rates between Arg/Arg and Arg/Cys genotypes, but nine Arg/Cys patients opted out of thiopurine treatment. In the Genotyping group, Arg/Arg patients received higher initial doses than the Non-genotyping group, while Arg/Cys patients received lower ones (median 25 mg/day). Fewer AEs occurred in the Genotyping group because of their lower incidence in Arg/Cys cases. Starting with < 25 mg/day of AZA reduced AEs in Arg/Cys patients, while Arg/Arg patients had better retention rates when maintaining ≥ 75 mg AZA. Nausea and liver injury correlated with thiopurine formulation but not dosage. pH-dependent mesalamine reduced leukopenia risk in mesalamine users.
CONCLUSIONS
NUDT15 codon 139 genotyping effectively reduces thiopurine-induced AEs and improves treatment retention rates in IBD patients after genotype-based dose adjustments. This study provides data-driven treatment strategies based on genotype and identifies risk factors for specific AEs, contributing to a refined thiopurine treatment approach.
Topics: Humans; Pyrophosphatases; Female; Male; Retrospective Studies; Adult; Middle Aged; Mercaptopurine; Genotype; Inflammatory Bowel Diseases; Japan; Azathioprine; Young Adult; Aged; Immunosuppressive Agents; Adolescent; Risk Factors; Codon; Nudix Hydrolases
PubMed: 38589597
DOI: 10.1007/s00535-024-02099-7 -
Frontiers in Oncology 2024Polymorphisms in may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the (c.415C>T; rs116855232) polymorphism...
INTRODUCTION
Polymorphisms in may result in differences in mercaptopurine-induced toxicity. This study aimed to identify the frequency of the (c.415C>T; rs116855232) polymorphism and investigate the effect of this polymorphism on mercaptopurine-induced toxicity in a population of Syrian patients with childhood acute lymphoblastic leukemia (ALL).
METHODS
This is a retrospective study that included children with ALL reaching at least 6 months of maintenance therapy. The genotyping was determined using standard targeted sequencing of polymerase chain reaction products. The odds ratio (OR) for the association between toxicity and genotype was evaluated.
RESULTS
A total of 92 patients were enrolled. The majority of the patients in the study population were low-risk (63.04%), followed by intermediate-risk (25%), and high-risk (11.96%). There were 5 patients (5.4%) with (c.415C>T; rs116855232) CT genotype, and 1 patient (1.08%) with TT genotype, with allele frequencies of C=0.962 and T=0.038. The mercaptopurine median dose intensity was 100%, 54.69%, and 5% for the genotypes CC, CT, and TT, respectively (=0.009). Early onset leukopenia was significantly associated with the polymorphism (OR: 6.16, 95% CI: 1.11-34.18, =0.037). There was no association between the genotype and hepatotoxicity.
CONCLUSION
Approximately 6.5% of the study population exhibited reduced NUDT15 activity. The mercaptopurine dose intensity was considerably low in rs116855232 TT genotype compared with CT and CC. The dosage of mercaptopurine should be adjusted according to the genotype in pediatric patients with ALL.
PubMed: 38562167
DOI: 10.3389/fonc.2024.1334846