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Journal of Hepatology Jul 2024
Reply to: Comments on "An open-label randomised-controlled trial of azathioprine vs. mycophenolate mofetil for the induction of remission in treatment-naive autoimmune hepatitis".
Topics: Humans; Mycophenolic Acid; Hepatitis, Autoimmune; Azathioprine; Immunosuppressive Agents; Randomized Controlled Trials as Topic; Remission Induction
PubMed: 38554845
DOI: 10.1016/j.jhep.2024.03.038 -
Pediatric Transplantation May 2024This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney...
Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.
BACKGROUND
This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs).
METHODS
This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate.
RESULTS
A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m, p = .614).
CONCLUSIONS
These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.
Topics: Humans; Child; Basiliximab; Antilymphocyte Serum; Antibodies, Monoclonal; Prednisone; Kidney Transplantation; Retrospective Studies; Cohort Studies; Azathioprine; Induction Chemotherapy; Graft Rejection; Immunosuppressive Agents; Recombinant Fusion Proteins; Transplant Recipients
PubMed: 38553819
DOI: 10.1111/petr.14713 -
Frontiers in Pharmacology 2024Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug...
Some herbal ingredients can reshape the composition of the gut microbiome as well as its metabolites. At the same time, the gut microbiota can also affect drug metabolism. A large number of studies have reported that saponins are biotransformed under the action of intestinal microorganisms to improve drug efficacy and bioavailability. Capilliposide A is a triterpenoid saponin, which is derived from Lysimachia Hemsl. CPS-A has anti-inflammatory pharmacological activity, but the substance basis is unknown at present, so studies on the interaction between intestinal microorganisms and CPS-A may clarify the pharmacodynamic substance basis of CPS-A. This study established a colitis mouse model, collected sterile feces from normal mice and colitis mice, and incubated CPS-A with two different intestinal flora . Based on LC-MS, the metabolic process of CPS-A mediated by intestinal microbes and the intervention effect of CPS-A on intestinal microbiome derived metabolites were studied. The results of experiments indicate that intestinal microorganisms can mediate the biotransformation of CPS-A and metabolize it into corresponding deglycosylation products, thereby promoting its drug effect. Not only that, CPS-A can also promote metabolites such as Deoxycholic acid, Histamine, 3-Hydroxytridecanoic acid, and Indole-3-acetic acid in the intestinal microbiota of mice with colitis. This may result in anti-colitis effects. CPS-A mainly involved in metabolic pathways such as azathioprine and mercaptopurine, which may also have beneficial or adverse effects. This study on the interaction between CPS-A and microbiota provides a new idea for the study of traditional Chinese medicine with poor oral bioavailability. The regulatory effect of CPS-A on the metabolites of intestinal flora in colitis mice was also found. It laid a foundation for exploring the mechanism of action of saponins on colitis mice.
PubMed: 38549666
DOI: 10.3389/fphar.2024.1361643 -
BMJ Case Reports Mar 2024Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same...
Autoimmune disorders have a wide spectrum of symptoms, often with multiorgan involvement. Multiple autoimmune disorders also often occur concurrently in the same patient. These two possibilities must be distinguished in patients with multiorgan involvement to ensure early diagnosis and treatment. Here, we report a case of a previously healthy man who presented with simultaneous Takayasu arteritis and Crohn's disease. He presented with heart failure with reduced ejection fraction and severe aortic regurgitation. An echocardiogram demonstrated a greatly dilated aorta, and a diagnosis of Takayasu arteritis was made, confirmed with CT aortogram. Inpatient treatment was begun, but the patient subsequently developed bloody diarrhoea a few days after admission. Colonoscopy done to locate the source of bleeding showed colonic ulcers; a biopsy confirmed a diagnosis of Crohn's disease. The patient was successfully managed with medical management of heart failure, steroids, mesalamine and azathioprine, and has been in remission for the last 2 years.
Topics: Male; Middle Aged; Humans; Crohn Disease; Takayasu Arteritis; Azathioprine; Heart Failure; Autoimmune Diseases
PubMed: 38531553
DOI: 10.1136/bcr-2023-259110 -
Journal of Endodontics Jun 2024Autoimmune liver diseases (ALDs) are chronic conditions generated by an immune-mediated autoaggressive inflammatory reaction in genetically susceptible individuals. The...
INTRODUCTION
Autoimmune liver diseases (ALDs) are chronic conditions generated by an immune-mediated autoaggressive inflammatory reaction in genetically susceptible individuals. The purpose of this study was to evaluate the prevalence of apical periodontitis (AP) in patients suffering from ALDs undergoing treatment with the immune suppressants glucocorticoids, azathioprine, and/or ursodeoxycholic acid.
METHODS
The ALD group included 46 patients (11 men and 35 women, average age = 57.9 ± 11.8 years) and 1186 teeth. The control group included 50 healthy patients not taking any medications (15 men and 35 women, average age = 58.6 ± 10.4 years) and 1251 teeth. Demographic data and medical, pharmacologic, and dental history were recorded. Dental and radiographic examinations were performed. The presence of AP; the periapical index score; decayed, missing, and filled teeth; quality of restoration, and root canal treatment were evaluated. The influence of the medications the patients were taking on the prevalence of AP was also tested.
RESULTS
The prevalence of AP was significantly lower in ALDs than in the control group at the patient (P = .019) and tooth level (P = .014). Smoking and age were associated with a significant increase in AP in cases and controls (P = .045 and P = .001, respectively). In both groups, endodontically treated teeth showed a higher prevalence of AP.
CONCLUSIONS
Considering the limitations because of the observational nature of the study, the patients affected by ALDs liver diseases and undergoing treatment with immune suppressors (often associated with immune modulators) were found to exhibit a lower prevalence of AP.
Topics: Humans; Periapical Periodontitis; Male; Female; Middle Aged; Cross-Sectional Studies; Prevalence; Immunosuppressive Agents; Autoimmune Diseases; Aged; Liver Diseases; Azathioprine; Ursodeoxycholic Acid; Glucocorticoids; Adult
PubMed: 38527610
DOI: 10.1016/j.joen.2024.02.026 -
Alimentary Pharmacology & Therapeutics Apr 2024
Topics: Humans; Thioguanine; Azathioprine; Antimetabolites, Antineoplastic; Inflammatory Bowel Diseases; Mercaptopurine
PubMed: 38523080
DOI: 10.1111/apt.17920 -
Rheumatology International Jun 2024Giant cell arteritis (GCA), more common in Northern European populations, has limited data in Arabcountries. Our study reports GCA's clinical manifestations in Jordan...
Giant cell arteritis (GCA), more common in Northern European populations, has limited data in Arabcountries. Our study reports GCA's clinical manifestations in Jordan and reviews published research on GCA across Arab nations. In this retrospective analysis, GCA patients diagnosed from January 2007 to March 2019 at a Jordanian academic medical center were included through referrals for temporal artery biopsy (TAB). A comprehensive search in PubMed, Scopus, and the DOAJ (Directory of Open Access Journals) databases was conducted to identify all relevant English-language manuscripts from Arab countries on GCA without time limitations. Among 59 diagnosed GCA patients, 41 (69.5%) were clinically diagnosed with a negative TAB, and 19 (30.5%) had a positive result. Females comprised 74.6% (n = 44) with 1:3 male-female ratio. The mean age at diagnosis was 67.3 (± 9.5) years, with most presenting within two weeks (n = 40, 67.8%). Headache was reported by 54 patients (91.5%). Elevated ESR occurred in 51 patients (78%), with a mean of 81 ± 32.2 mm/hr. All received glucocorticoids for 13.1 ± 10 months. Azathioprine, Methotrexate, and Tocilizumab usage was 15.3% (n = 9), 8.5% (n = 5), and 3.4% (n = 2), respectively. Remission was observed in 57.6% (n=34), and 40.7% (n = 24) had a chronic clinical course on treatment. Males had higher biopsy-based diagnoses (p = .008), and biopsy-diagnosed patients were older (p = .043). The literature search yielded only 20 manuscripts originating in the Arab world. The predominant study types included case reports and retrospective analyses, with only one case series and onecase-control study.
Topics: Humans; Giant Cell Arteritis; Male; Retrospective Studies; Female; Aged; Middle Aged; Temporal Arteries; Jordan; Glucocorticoids; Immunosuppressive Agents; Methotrexate; Biopsy; Azathioprine; Antibodies, Monoclonal, Humanized
PubMed: 38502233
DOI: 10.1007/s00296-024-05540-5 -
Saudi Pharmaceutical Journal : SPJ :... Apr 2024Single nucleotide polymorphisms in the gene encoding proteins involved in mercaptopurine metabolism can influence drug efficacy and safety. This study aims to assess...
BACKGROUND
Single nucleotide polymorphisms in the gene encoding proteins involved in mercaptopurine metabolism can influence drug efficacy and safety. This study aims to assess clinical pharmacists' knowledge about mercaptopurine-related genes and their polymorphisms and investigate their attitudes, perceptions, and beliefs about the need for and importance of pharmacogenetic testing for mercaptopurine.
METHODS
A cross-sectional descriptive study was conducted among oncology/hematology clinical pharmacists in Saudi Arabia using an online-questionnaire developed by experts in the field. The questionnaire consists of four-sections exploring clinical pharmacists' knowledge, attitudes, perceptions, and beliefs about the importance of gene testing and genes polymorphism when prescribing mercaptopurine. Descriptive statistics were used to analyze the data in the study.
RESULTS
A total of 41 oncology/hematology clinical pharmacists responded to the survey invitation. Almost half of them had more than 10 years of work experience, but only 17 % of them received formal training in pharmacogenetics. The overall level of knowledge about pharmacogenetics among participants was low, with a mean score of 2.8 points (1.7) out of 8 items. However, around 76 % agreed that it is important to perform pharmacogenetic screening prior to prescribing mercaptopurine, and almost 93 % state that it will influence their dosage recommendation. Most of the participants had a good perception (95.1 %) of their role in genetic testing for medication selection, dosing, and monitoring; however, about 10 % of surveyed pharmacists reported not being completely responsible about recommending pharmacogenetic testing. The surveyed pharmacists had a good belief in the importance of pharmacogenetic testing and their overall attitude was positive toward the use of pharmacogenetic testing, with emphasis on the importance of training on the proper assessment and interpretation of pharmacogenetic tests.
CONCLUSIONS
Pharmacists demonstrated good perception and positive attitude toward pharmacogenetic testing, despite the low level of knowledge and limited formal training. Thus, more attention to developing national guidelines on pharmacogenetic testing is warranted to ensure successful pharmacogenetic testing implementation.
PubMed: 38497085
DOI: 10.1016/j.jsps.2024.102022 -
Cell Death & Disease Mar 2024Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and...
Despite progressive improvements in the survival rate of pediatric B-cell lineage acute lymphoblastic leukemia (B-ALL), chemoresistance-induced disease progression and recurrence still occur with poor prognosis, thus highlighting the urgent need to eradicate drug resistance in B-ALL. The 6-mercaptopurine (6-MP) is the backbone of ALL combination chemotherapy, and resistance to it is crucially related to relapse. The present study couples chemoresistance in pediatric B-ALL with histidine metabolism deficiency. Evidence was provided that histidine supplementation significantly shifts the 6-MP dose-response in 6-MP-resistant B-ALL. It is revealed that increased tetrahydrofolate consumption via histidine catabolism partially explains the re-sensitization ability of histidine. More importantly, this work provides fresh insights into that desuccinylation mediated by SIRT5 is an indispensable and synergistic requirement for histidine combination therapy against 6-MP resistance, which is undisclosed previously and demonstrates a rational strategy to ameliorate chemoresistance and protect pediatric patients with B-ALL from disease progression or relapse.
Topics: Humans; Child; Mercaptopurine; Histidine; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Burkitt Lymphoma; Recurrence; Disease Progression; Sirtuins
PubMed: 38485947
DOI: 10.1038/s41419-024-06599-5 -
Seminars in Respiratory and Critical... Jun 2024Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for... (Review)
Review
Interstitial lung disease (ILD) is a common pulmonary complication of rheumatoid arthritis (RA), causing significant morbidity and mortality. Optimal treatment for RA-ILD is not yet well defined. Reliable prognostic indicators are largely byproducts of prior ILD progression, including low or decreasing forced vital capacity and extensive or worsening fibrosis on imaging. In the absence of validated tools to predict treatment response, decisions about whether to initiate or augment treatment are instead based on clinical judgment. In general, treatment should be initiated in patients who are symptomatic, progressing, or at high risk of poor outcomes. Retrospective data suggest that mycophenolate mofetil, azathioprine, and rituximab are likely effective therapies for RA-ILD. Abatacept is also emerging as a potential first-line treatment option for patients with RA-ILD. Further, recent data demonstrate that immunosuppression may be beneficial even in patients with a usual interstitial pneumonia (UIP) pattern on imaging, suggesting that immunosuppression should be considered irrespective of imaging pattern. Recent randomized controlled trials have shown that antifibrotic medications, such as nintedanib and likely pirfenidone, slow forced vital capacity decline in RA-ILD. Consideration can be given to antifibrotic initiation in patients progressing despite immunosuppression, particularly in patients with a UIP pattern. Future research directions include developing tools to predict which patients will remain stable from patients who will progress, discriminating patients who will respond to treatment from nonresponders, and developing algorithms for starting immunosuppression, antifibrotics, or both as first-line therapies.
Topics: Humans; Lung Diseases, Interstitial; Arthritis, Rheumatoid; Immunosuppressive Agents; Disease Progression; Antirheumatic Agents; Abatacept; Prognosis; Mycophenolic Acid; Rituximab; Vital Capacity; Pyridones; Randomized Controlled Trials as Topic; Azathioprine; Indoles
PubMed: 38484788
DOI: 10.1055/s-0044-1782218