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Haematologica Jul 2024
Mycophenolate mofetil is associated with inferior overall survival in cytomegalovirus-seropositive patients with acute myeloid leukemia undergoing hematopoietic cell transplantation.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Mycophenolic Acid; Cytomegalovirus Infections; Male; Female; Middle Aged; Cytomegalovirus; Adult; Aged; Immunosuppressive Agents
PubMed: 38426274
DOI: 10.3324/haematol.2023.284501 -
Case Reports in Nephrology and Dialysis 2024Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case...
INTRODUCTION
Mycophenolate mofetil (MMF), an inactive prodrug of mycophenolic acid (MPA), is an immunosuppressive drug used widely in the treatment of lupus nephritis. In this case report, the area under the blood concentration time curve (AUC) of MPA was significantly decreased by the concomitant use of sacubitril/valsartan.
CASE PRESENTATION
The patient was a man in his 40s with a diagnosis of lupus nephritis class IVa/c+V. MMF dose was 1.5 g/day at admission, and AUC of MPA on day 14 was 25.1 μg⋅h/mL. Owing to poor blood pressure control, sacubitril/valsartan was initiated at 97/103 mg/day on day 29. On day 37, AUC of MPA was significantly decreased to 8.7 μg⋅h/mL, suggesting drug interaction with the newly initiated sacubitril/valsartan. Sacubitril/valsartan was decreased to 49/51 mg/day, and AUC of MPA on day 67 was 37.6 μg⋅h/mL, achieving the target range. The final MMF dose was set at 1.75 g/day. A possible mechanism of drug interaction between sacubitril/valsartan and MPA involves an organic anion transporting polypeptide (OATP). The inhibition of OATPs by sacubitril may have interrupted the enterohepatic circulation of MPA, resulting in a lower plasma concentration.
CONCLUSION
Since lupus nephritis is often associated with hypertension, the drug interaction observed in this report may also occur in other cases. However, it is impossible to conclude that the decrease in plasma MPA levels was due to the concomitant use of sacubitril/valsartan, and more cases and basic findings are needed.
PubMed: 38420337
DOI: 10.1159/000536468 -
Journal of Microbiology and... Feb 2024New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic...
New anti-lung cancer therapies are urgently required to improve clinical outcomes. Since ganodermanontriol (GDNT) has been identified as a potential antineoplastic agent, its role in lung adenocarcinoma (LUAD) is investigated in this study. Concretely, lung cancer cells were treated with GDNT and/or mycophenolate mofetil (MMF), after which MTT assay, flow cytometry and Western blot were conducted. Following bioinformatics analysis, carboxylesterase 2 (CES2) was knocked down and rescue assays were carried out in vitro. Xenograft experiment was performed on mice, followed by drug administration, measurement of tumor growth and determination of CES2, IMPDH1 and IMPDH2 expressions. As a result, the viability of lung cancer cells was reduced by GDNT or MMF. GDNT enhanced the effects of MMF on suppressing viability, promoting apoptosis and inducing cell cycle arrest in lung cancer cells. GDNT up-regulated CES2 level, and strengthened the effects of MMF on down-regulating IMPDH1 and IMPDH2 levels in the cells. IMPDH1 and IMPDH2 were highly expressed in LUAD samples. CES2 was a potential target for GDNT. CES2 knockdown reversed the synergistic effect of GDNT and MMF against lung cancer in vitro. GDNT potentiated the role of MMF in inhibiting tumor growth and expressions of CES2 and IMPDH1/2 in lung cancer in vivo. Collectively, GDNT suppresses the progression of LUAD by activating CES2 to enhance the metabolism of MMF.
Topics: Humans; Animals; Mice; Mycophenolic Acid; Antineoplastic Agents; Adenocarcinoma of Lung; Lung Neoplasms; Carboxylesterase; Lanosterol
PubMed: 38419324
DOI: 10.4014/jmb.2306.06020 -
Frontiers in Immunology 2024Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of...
INTRODUCTION
Kidney transplant recipients (KTRs) are at a higher risk of severe coronavirus disease (COVID-19) because of their immunocompromised status. However, the effect of allograft function on the prognosis of severe COVID-19 in KTRs is unclear. In this study, we aimed to analyze the correlation between pre-infection allograft function and the prognosis of severe COVID-19 in KTRs.
METHODS
This retrospective cohort study included 82 patients who underwent kidney transplantation at the Sichuan Provincial Peoples Hospital between October 1, 2014 and December 1, 2022 and were diagnosed with severe COVID-19. The patients were divided into decreased eGFR and normal eGFR groups based on the allograft function before COVID-19 diagnosis (n=32 [decreased eGFR group], mean age: 43.00 years; n=50 [normal eGFR group, mean age: 41.88 years). We performed logistic regression analysis to identify risk factors for death in patients with severe COVID-19. The nomogram was used to visualize the logistic regression model results.
RESULTS
The mortality rate of KTRs with pre-infection allograft function insufficiency in the decreased eGFR group was significantly higher than that of KTRs in the normal eGFR group (31.25% [10/32] vs. 8.00% [4/50], =0.006). Pre-infection allograft function insufficiency (OR=6.96, 95% CI: 1.4633.18, =0.015) and maintenance of a mycophenolic acid dose >1500 mg/day before infection (OR=7.59, 95% CI: 1.0853.20, =0.041) were independent risk factors, and the use of nirmatrelvir/ritonavir before severe COVID-19 (OR=0.15, 95% CI: 0.030.72, =0.018) was a protective factor against death in severe COVID-19.
CONCLUSIONS
Pre-infection allograft function is a good predictor of death in patients with severe COVID-19. Allograft function was improved after treatment for severe COVID-19, which was not observed in patients with non-severe COVID-19.
Topics: Humans; Adult; Kidney Transplantation; Retrospective Studies; COVID-19 Testing; COVID-19; Risk Factors; Allografts
PubMed: 38415244
DOI: 10.3389/fimmu.2024.1335148 -
BMJ Open Respiratory Research Feb 2024Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Mycophenolate mofetil (MMF) and azathioprine (AZA) are immunomodulatory treatments in interstitial lung disease (ILD). This systematic review aimed to evaluate the efficacy of MMF or AZA on pulmonary function in ILD.
DESIGN
Population included any ILD diagnosis, intervention included MMF or AZA treatment, outcome was delta change from baseline in per cent predicted forced vital capacity (%FVC) and gas transfer (diffusion lung capacity of carbon monoxide, %DLco). The primary endpoint compared outcomes relative to placebo comparator, the secondary endpoint assessed outcomes in treated groups only.
ELIGIBILITY CRITERIA
Randomised controlled trials (RCTs) and prospective observational studies were included. No language restrictions were applied. Retrospective studies and studies with high-dose concomitant steroids were excluded.
DATA SYNTHESIS
The systematic search was performed on 9 May. Meta-analyses according to drug and outcome were specified with random effects, I evaluated heterogeneity and Grading of Recommendations, Assessment, Development and Evaluation evaluated certainty of evidence. Primary endpoint analysis was restricted to RCT design, secondary endpoint included subgroup analysis according to prospective observational or RCT design.
RESULTS
A total of 2831 publications were screened, 12 were suitable for quantitative synthesis. Three MMF RCTs were included with no significant effect on the primary endpoints (%FVC 2.94, 95% CI -4.00 to 9.88, I=79.3%; %DLco -2.03, 95% CI -4.38 to 0.32, I=0.0%). An overall 2.03% change from baseline in %FVC (95% CI 0.65 to 3.42, I=0.0%) was observed in MMF, and RCT subgroup summary estimated a 4.42% change from baseline in %DL (95% CI 2.05 to 6.79, I=0.0%). AZA studies were limited. All estimates were considered very low certainty evidence.
CONCLUSIONS
There were limited RCTs of MMF or AZA and their benefit in ILD was of very low certainty. MMF may support preservation of pulmonary function, yet confidence in the effect was weak. To support high certainty evidence, RCTs should be designed to directly assess MMF efficacy in ILD.
PROSPERO REGISTRATION NUMBER
CRD42023423223.
Topics: Humans; Azathioprine; Immunosuppressive Agents; Lung Diseases, Interstitial; Lung; Mycophenolic Acid; Enzyme Inhibitors; Observational Studies as Topic
PubMed: 38413120
DOI: 10.1136/bmjresp-2023-002163 -
Transplantation Reviews (Orlando, Fla.) Apr 2024The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement... (Review)
Review
The complement system is part of innate immunity and is pivotal in protecting the body against pathogens and maintaining host homeostasis. Activation of the complement system is triggered through multiple pathways, including antibody deposition, a mannan-binding lectin, or activated complement deposition. C3 glomerulopathy (C3G) is a rare glomerular disease driven by complement dysregulation with high post-transplantation recurrence rates. Its treatment is mainly based on immunosuppressive therapies, specifically mycophenolate mofetil and glucocorticoids. Recent years have seen significant progress in understanding complement biology and its role in C3G pathophysiology. New complement-tergeting treatments have been developed and initial trials have shown promising results. However, challenges persist in C3G, with recurrent post-transplantation cases leading to suboptimal outcomes. This review discusses the pathophysiology and management of C3G, with a focus on its recurrence after kidney transplantation.
Topics: Humans; Kidney Transplantation; Complement C3; Glomerulonephritis, Membranoproliferative; Kidney Diseases; Mycophenolic Acid
PubMed: 38412598
DOI: 10.1016/j.trre.2024.100839 -
Current Opinion in Nephrology and... May 2024As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently,... (Review)
Review
PURPOSE OF REVIEW
As the most common primary glomerulonephritis, immunoglobulin A (IgA) nephropathy (IgAN) is an important cause of kidney failure and mortality. Until recently, therapeutic options were limited. Fortunately, there have been numerous recent clinical trials demonstrating efficacy of new therapies in slowing chronic kidney disease (CKD) progression at varying stages of disease.
RECENT FINDINGS
The TESTING trial has provided high-quality evidence for slowing estimated glomerular filtration rate (eGFR) decline with a reduced-dose glucocorticoid regimen, while demonstrating an improved safety profile. Targeted-release budesonide represents a well tolerated therapy for reducing eGFR decline. Mycophenolate mofetil may reduce CKD progression in some populations, while hydroxychloroquine is efficacious in reducing proteinuria. Sodium-glucose cotransporter (SGLT2) inhibitors and sparsentan are effective therapies for CKD due to IgAN, but should not be used in lieu of disease-modifying immunosuppressive therapy. Many new therapies are approaching readiness for clinical use.
SUMMARY
Numerous therapeutic options now exist and include disease-modifying and nephroprotective drugs. Identifying the right treatment for the right patient is now the clinical challenge and, with new drugs on the horizon, represents the primary unmet research need in this rapidly-developing field.
Topics: Humans; Glomerulonephritis, IGA; Standard of Care; Renal Insufficiency, Chronic; Mycophenolic Acid; Glucocorticoids; Proteinuria
PubMed: 38411173
DOI: 10.1097/MNH.0000000000000979 -
Transplant Infectious Disease : An... Apr 2024We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery...
We present a case of a 72-year-old liver transplant recipient 7 years prior who presents to our hospital with general malaise, fatigue, low-grade fevers, and watery diarrhea. He was found to have Astrovirus via PCR testing in a comprehensive stool panel. The patient's home mycophenolic acid was held upon admission, while cyclosporine was continued through his hospital stay. Generally, Astroviridae infection is a rarely identified cause of enteritis and even less so in the transplant population. Although reports have been published regarding devastating cases of encephalitis in immunocompromised patients, our patient did not exhibit these symptoms and draws into question the danger of this virus in other immunosuppressed populations. This case helps to better elucidate which patient populations should be approached with caution in the setting of Astroviridae infection.
Topics: Male; Humans; Aged; Astroviridae; Astroviridae Infections; Liver Transplantation; Diarrhea; Enteritis; Organ Transplantation
PubMed: 38407512
DOI: 10.1111/tid.14257 -
Journal of Ayub Medical College,... 2023We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers,...
We present the case of a 30-year-old woman who presented with 8-month history of intermittent fever, joint pains with morning stiffness, recurrent oral ulcers, photosensitivity, weight loss and hair fall. For the last 2 months, she had developed a dry cough with progressive shortening of breath. On examination, a cachexic lady with malar hyperpigmentation, alopecia, pallor, nail dystrophy and erythema over her hands and feet were noted. There were multiple punched-out skin ulcers of variable size over legs, arms and abdomen usually round in shape with well-defined even wound margins and scant serous discharge. Musculoskeletal examination revealed synovitis of both elbows and a few metacarpophalangeal and proximal interphalangeal joints. Chest X-ray and HRCT showed bilateral ground-glass opacification. Anti-Nuclear Antibody (ANA) was positive, 1:320, homogenous nuclear pattern. Anti-Ro antibody was highly positive and serum complement (C3, C4) levels were reduced. She was diagnosed with Lupus Vasculitis and started on steroids, mycophenolate mofetil and hydroxychloroquine.
Topics: Humans; Female; Adult; Cellulitis; Impetigo; Pakistan; Eye Diseases; Mycophenolic Acid
PubMed: 38404102
DOI: 10.55519/JAMC-03-11426 -
Journal of Ayub Medical College,... 2023A multi-organ granulomatous disease with characteristic lung manifestations, sarcoidosis generally responds well to glucocorticoid therapy but 10% of cases are...
A multi-organ granulomatous disease with characteristic lung manifestations, sarcoidosis generally responds well to glucocorticoid therapy but 10% of cases are refractory necessitating immunosuppressive therapy. A 58-year-old lady presented with a dry cough and progressively worsening shortness of breath for the last 12 months. On investigation, her ESR was raised but cultures, malignancy screen and TB quantiferon were negative. HRCT chest demonstrated multiple pulmonary nodules with hilar lymphadenopathy and CT guided biopsy revealed non-caseating granuloma. She was diagnosed with Pulmonary Sarcoidosis and started on oral steroids with minimal improvement. Azathioprine was added but due to gastric intolerance switched to methotrexate. Her disease however continued to worsen and infliximab was started but she developed a severe allergic reaction. She was then started on mycophenolate mofetil but her chest imaging continued to worsen. After failing prednisone, azathioprine, methotrexate, infliximab and mycophenolate mofetil, the patient was started on rituximab.
Topics: Humans; Female; Middle Aged; Methotrexate; Infliximab; Mycophenolic Acid; Azathioprine; Sarcoidosis; Granuloma
PubMed: 38404097
DOI: No ID Found