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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; Mycophenolic Acid; Fever; Arthralgia; Vasculitis
PubMed: 38404096
DOI: 10.55519/JAMC-03-10849 -
Journal of Hepatology Jul 2024
Topics: Humans; Hepatitis, Autoimmune; Immunosuppressive Agents; Mycophenolic Acid
PubMed: 38403032
DOI: 10.1016/j.jhep.2024.02.014 -
Journal of Hepatology Jul 2024
Topics: Humans; Mycophenolic Acid; Azathioprine; Hepatitis, Autoimmune; Immunosuppressive Agents; Remission Induction
PubMed: 38403031
DOI: 10.1016/j.jhep.2024.02.012 -
International Journal of Antimicrobial... May 2024Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem...
Human adenovirus (HAdV) and cytomegalovirus (HCMV) cause high morbidity and mortality in patients undergoing solid organ transplantation (SOT) and haematopoietic stem cell transplantation (HSCT). Immunosuppressors are used universally to prevent graft-vs-host disease in HSCT and graft rejection in SOT. The long-term use of these drugs is associated with a high risk of infection, but there is also evidence of their specific interference with viral infection. This study evaluated the antiviral activity of immunosuppressors commonly used in clinical practice in SOT and HSCT recipients in vitro to determine whether their use could be associated with reduced risk of HAdV and HCMV infection. Cyclophosphamide, tacrolimus, cyclosporine, mycophenolic acid, methotrexate, everolimus and sirolimus presented antiviral activity, with 50% inhibitory concentration (IC) values at low micromolar and sub-micromolar concentrations. Mycophenolic acid and methotrexate showed the greatest antiviral effects against HAdV (IC=0.05 µM and 0.3 µM, respectively) and HCMV (IC=10.8 µM and 0.02 µM, respectively). The combination of tacrolimus and mycophenolic acid showed strong synergistic antiviral activity against both viruses, with combinatory indexes (CI) of 0.02 and 0.25, respectively. Additionally, mycophenolic acid plus cyclosporine, and mycophenolic acid plus everolimus/sirolimus showed synergistic antiviral activity against HAdV (CI=0.05 and 0.09, respectively), while methotrexate plus cyclosporine showed synergistic antiviral activity against HCMV (CI=0.29). These results, showing antiviral activity in vitro against both HAdV and HCMV, at concentrations below the human C values, may be relevant for the selection of specific immunosuppressant therapies in patients at risk of HAdV and HCMV infections.
Topics: Humans; Immunosuppressive Agents; Antiviral Agents; Adenoviruses, Human; Cytomegalovirus; Drug Synergism; Inhibitory Concentration 50; Mycophenolic Acid; Tacrolimus; Cyclosporine; Cytomegalovirus Infections
PubMed: 38401774
DOI: 10.1016/j.ijantimicag.2024.107116 -
International Journal of Molecular... Feb 2024Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple...
Immunosuppression management in transplant recipients is a critical component of pharmacotherapy. This becomes particularly crucial when patients are exposed to multiple medications that may lead to pharmacological interactions, potentially compromising the effectiveness of immunosuppression. We present the case of a 46-year-old patient diagnosed with cystic fibrosis in childhood at our hospital, who underwent bilateral lung transplantation and is undergoing immunosuppressive therapy. The patient was hospitalized due to an acute pulmonary exacerbation. During the hospitalization, the patient was administered various classes of antibiotics while continuing the standard antirejection regimen of everolimus and mycophenolate. Plasma concentrations of immunosuppressants, measured after antibiotic therapy, revealed significantly lower levels than the therapeutic thresholds, providing the basis for formulating the hypothesis of a drug-drug interaction phenomenon. This hypothesis is supported by the rationale of antibiotic-induced disruption of the intestinal flora, which directly affects the kinetics of mycophenolate. These levels increased after discontinuation of the antimicrobials. Patients with CF undergoing lung transplantation, especially prone to pulmonary infections due to their medical condition, considering the enterohepatic circulation of mycophenolate mediated by intestinal bacteria, necessitate routine monitoring of mycophenolate concentrations during and immediately following the cessation of antibiotic therapies, that could potentially result in insufficient immunosuppression.
Topics: Humans; Middle Aged; Mycophenolic Acid; Cystic Fibrosis; Anti-Bacterial Agents; Immunosuppressive Agents; Lung Transplantation; Enzyme Inhibitors
PubMed: 38397035
DOI: 10.3390/ijms25042358 -
Transplantation Proceedings Mar 2024To describe and establish the efficacy and safety of Mycophenolate Mofetil (Micoflavin) in patients with de novo renal transplantation during one-year post-transplant...
BACKGROUND
To describe and establish the efficacy and safety of Mycophenolate Mofetil (Micoflavin) in patients with de novo renal transplantation during one-year post-transplant follow-up. As secondary objectives, the behavior of mycophenolic acid (MPA) C0 levels in this population, the relationship between MPA levels and renal function of the grafts, the incidence of acute rejection, and the incidence of adverse effects were evaluated.
METHODS
A prospective cohort study was conducted on patients who received a first kidney transplant from a deceased donor between March 1, 2021, and February 28, 2022, at the Alma Mater of Antioquia Hospital of the Antioquia's University, in Medellín, Colombia. MPA C0 levels were taken from the patients on days 15, 30, 90, 180, and 360 after the kidney transplantation.
RESULTS
Patients presented MPA therapeutic levels in the study. The average of the MPA levels in the population was 2.5 µg/mL, with an IQR of 2.13 to 3.32. There were 5 acute rejections (27%), but none of the patients with acute rejection presented subtherapeutic levels of mycophenolate. No significant relationship was observed between mycophenolic acid levels and rejection (P = .255). The patients who completed the study had no gastrointestinal intolerance to mycophenolate, cytomegalovirus infections, or significant hematological complications.
CONCLUSIONS
MMF (Micoflavin) maintained mycophenolic acid levels C0 within the therapeutic range, was well tolerated and without the presence of significant adverse events, and maintained stable renal function throughout the follow-up period in the population studied.
Topics: Humans; Mycophenolic Acid; Kidney Transplantation; Retrospective Studies; Transplant Recipients; Prospective Studies; Colombia; Immunosuppressive Agents; Enzyme Inhibitors; Graft Rejection
PubMed: 38395659
DOI: 10.1016/j.transproceed.2023.12.019 -
Technology and Health Care : Official... Feb 2024Diarrhea is a prevalent complication after renal transplantation.
BACKGROUND
Diarrhea is a prevalent complication after renal transplantation.
OBJECTIVE
To examine the risk factors for diarrhea after renal transplantation, evaluate their combined predictive values, and analyze the prognosis.
METHODS
Clinical data of patients who underwent allogeneic renal transplantation in the Second People's Hospital of Shanxi Province from January 2019 to March 2020 were retrospectively analyzed, cases were screened and grouped, independent risk factors for diarrhea after renal transplantation were analyzed by univariate analysis and multivariate analysis, and their predictive value was evaluated by receiver operating characteristic (ROC) curve. The survival time of recipient grafts in diarrhea and non-diarrhea groups were evaluated by Kaplan-Meier and log-rank test.
RESULTS
We included 166 recipients in the study and the incidence of diarrhea was 25.9%; univariate and logistic regression multivariate analyses revealed that independent risk factors for diarrhea in recipients were that the type of renal transplant donor was DCD (donation after circulatory death), immunity induction was onducted with basiliximab + antithymocyte globulin (ATG), and ATG alone, the type of mycophenolic acid (MPA) used was mycophenolate mofetil capsules, and delayed graft function (DGF) occurred after transplantation. The ROC curve indicated that the combination of the four factors had good accuracy in predicting the occurrence of diarrhea in recipients. The graft survival rate two years after the operation in the diarrhea group was significantly lower than that in the non-diarrhea group.
CONCLUSION
Diarrhea affected the two-year survival rate of the graft. The type of donor, immunity induction scheme, and the type of MPA and DGF were independent risk factors for diarrhea in recipients, and the combination of the four factors had good prognostic prediction value.
PubMed: 38393930
DOI: 10.3233/THC-230579 -
Experimental and Clinical... Jan 2024Respiratory tract infections are life-threatening infections in solid-organ transplant recipients that pose risk to the graft and to the patient. This study was...
OBJECTIVES
Respiratory tract infections are life-threatening infections in solid-organ transplant recipients that pose risk to the graft and to the patient. This study was undertaken to examine the clinical and microbiological spectrum of pneumonia in renal transplant recipients.
MATERIALS AND METHODS
Of 400 consecutive renal transplant recipients, 87 recipients (21.8%) were hospitalized between November 2014 and October 2016 with pneumonia. We examined demographic profiles and clinical investigations.
RESULTS
The median age of patients was 38 years (range, 19-72 y). The mean time of presentation after renal transplant was 18 months (range, 1-174 mo). Most patients (80.5%) were on maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids; 34% of patients had an induction agent. Chronic hepatitis C and hepatitis B infections were found in 12.6% and 2.2% of patients, respectively, and new-onset diabetes in 19.5% of patients. Fever (88%), cough (87%), shortness of breath (68%), and hypotension (33%) were common presenting symptoms. Diarrhea was the most frequent accompanying symptom, found in 9.2% of patients. Cytopenia and graft dysfunction were present in 38.7% and 80.4% of patients. Among infections, fungal infections were the most frequent (30%) followed by mixed infections (20.7%), tuberculosis (12.6%), bacterial (12.6%), and viral (3.5%) infections. Etiology could not be found in 27.6% patients. Mortality rate was 24.1%, with the highest rates for fungal infections (44%), followed by bacterial (25%) and mixed infections (18%). Presence of hypoxia and hypotension at presentation was associated with increased risk of death, whereas use of induction agents, new-onset diabetes posttransplant, diabetes mellitus, and acute kidney injury were not correlated with death or increased duration of hospital stay.
CONCLUSIONS
Pneumonia carries high risk of mortality in renal transplant recipients. Fungal and bacterial infections carry high risk of mortality. Despite invasive investigations, a substantial number of patients had unidentified etiology.
Topics: Humans; Young Adult; Adult; Middle Aged; Aged; Immunosuppressive Agents; Kidney Transplantation; Coinfection; Mycophenolic Acid; Diabetes Mellitus; Pneumonia; Mycoses; Hypotension; Transplant Recipients; Graft Rejection
PubMed: 38385377
DOI: 10.6002/ect.MESOT2023.P49 -
Medicina Clinica May 2024Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with...
INTRODUCTION
Immune thrombocytopenia (ITP) is a potentially severe manifestation of systemic lupus erythematosus (SLE) reported in 7-40% of SLE patients. ITP has been associated with a higher risk of organ damage and mortality.
OBJECTIVES
To describe which factors are associated with the presence of ITP in SLE patients.
METHODS
Retrospective case-control study. Cases were defined as SLE patients who had ever developed ITP and were sex- and age-matched with two controls. A predictive model was constructed to identify SLE patients who were at risk of developing ITP.
RESULTS
ITP prevalence in our SLE cohort was 8.35%. Cases had a higher frequency of hemolytic anemia, while controls had a higher prevalence of arthritis at SLE diagnosis. During SLE progression, cases tested positive for anticardiolipin, anti-β2-glycoprotein 1, and lupus anticoagulant antibodies more frequently. Cases received mycophenolic acid and azathioprine more often than controls and had a higher SLICC/ACR score. The model demonstrated a sensitivity of 87.53%, a positive predictive value of 81.92%, a specificity of 80.50%, area under the curve of 83.92%, a F1 of 83% and an overall accuracy of 83.68%. The variables that best explain the model were hemolytic anemia, arthritis, oral ulcers, Raynaud's phenomenon, low C4, low CH50, anticardiolipin and anti-β2GP1 antibodies.
CONCLUSION
SLE patients who develop ITP have a distinct phenotype characterized by more hemolytic anemia and less arthritis at SLE onset, and higher prevalence of antiphospholipid syndrome antibodies during SLE progression. This phenotype is associated with heightened organ damage and the need for more intensive therapies and stricter follow-up. Our predictive model has demonstrated an impressive ability to identify SLE patients at risk of developing ITP.
Topics: Humans; Lupus Erythematosus, Systemic; Female; Retrospective Studies; Male; Adult; Prevalence; Case-Control Studies; Risk Assessment; Risk Factors; Purpura, Thrombocytopenic, Idiopathic; Middle Aged; Young Adult
PubMed: 38383267
DOI: 10.1016/j.medcli.2023.12.012 -
International Journal of Biological... Apr 2024Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been...
Mycophenolate mofetil (MMF) is a viable therapeutic option against various immune disorders as a chemotherapeutic agent. Nevertheless, its application has been undermined by the gastrotoxic metabolites (mycophenolic acid glucuronide, MPAG) produced by microbiome-associated β-glucuronidase (βGUS). Therefore, controlling microbiota-produced βGUS underlines the potential strategy to improve MMF efficacy by overcoming the dosage limitation. In this study, the octyl gallate (OG) was identified with promising inhibitory activity on hydrolysis of PNPG in our high throughput screening based on a chemical collection of approximately 2000 natural products. Furthermore, OG was also found to inhibit a broad spectrum of BGUSs, including mini-Loop1, Loop 2, mini-Loop 2, and mini-Loop1,2. The further in vivo experiments demonstrated that administration of 20 mg/kg OG resulted in predominant reduction in the activity of BGUSs while displayed no impact on the overall fecal microbiome in mice. Furthermore, in the MMF-induced colitis model, the administration of OG at a dosage of 20 mg/kg effectively mitigated the gastrointestinal toxicity, and systematically reverted the colitis phenotypes. These findings indicate that the OG holds promising clinical potential for the prevention of MMF-induced gastrointestinal toxicity by inhibition of BGUSs and could be developed as a combinatorial therapy with MFF for better clinical outcomes.
Topics: Mice; Animals; Mycophenolic Acid; Immunosuppressive Agents; Glucuronidase; Gastrointestinal Microbiome; Bacteria; Colitis; Gallic Acid
PubMed: 38382789
DOI: 10.1016/j.ijbiomac.2024.130145