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The Analyst Jun 2024Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is...
Sea urchin nanostructured nickel cobaltite modified carbon cloth integrated wearable patches for the on-site detection of the immunosuppressant drug mycophenolate mofetil.
Mycophenolate mofetil (MpM) is a medication used to prevent the rejection of transplanted organs, particularly in kidney, heart, and liver transplant surgeries. It is extremely important to be conscious that MpM can raise the risk of severe infections and some cancers if it exceeds the recommended dose while lower doses will result in organ rejections. So, it is essential to monitor the dosage of MpM in real time in the micromolar range. In this work, we have synthesized 3-aminopropyltriethoxysilane (APTES) functionalized nickel cobaltite (NiCoO) and this amino functionalization was chosen to enhance the stability and electrochemical activity of NiCoO. The enhanced activity of NiCoO was used for developing an electrochemical sensor for the detection of MpM. APTES functionalized NiCoO was coated on carbon cloth and used as the working electrode. Surface functionalization with APTES on NiCoO was aimed at augmenting the adsorption/interaction of MpM due to its binding properties. The developed sensor showed a very low detection limit of 1.23 nM with linear ranges of 10-100 nM and 1-100 μM and its practical applicability was examined using artificial samples of blood serum and cerebrospinal fluid, validating its potential application in real-life scenarios.
Topics: Animals; Nickel; Mycophenolic Acid; Immunosuppressive Agents; Carbon; Wearable Electronic Devices; Limit of Detection; Sea Urchins; Nanostructures; Electrochemical Techniques; Propylamines; Humans; Cobalt; Electrodes; Silanes
PubMed: 38775016
DOI: 10.1039/d4an00592a -
Case Reports in Rheumatology 2024Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet-colored skin patches to sclerotic plaques. Another uncommon...
BACKGROUND
Generalized morphea is a rare fibrosing skin illness that progresses from erythematous, violet-colored skin patches to sclerotic plaques. Another uncommon immune-mediated connective tissue disease called eosinophilic fasciitis (EF) evolves to cause sclerosis and woody skin induration. The coexistence of the two is extremely rare and has a poorer prognosis. Our case report is one of the first to report burn injuries as a trigger factor for EF and generalized morphea overlap. . A 36-year-old man presented with acute onset of rapidly progressing skin thickening, tender edema, and skin contractures involving all extremities, shortly after enduring burn injuries from a gasoline explosion. Workup was remarkable for peripheral eosinophilia, hypergammaglobulinemia, and elevated C-reactive protein. Skin biopsy demonstrated sclerodermoid changes and sclerotic thickening of subcutaneous fibrous septa associated with stromal mucin, dermal perivascular, diffuse lymphoplasmacytic infiltrate with eosinophils, decreased CD34 expression, and increased factor XIIIa. He was subsequently diagnosed with an overlap of generalized morphea and eosinophilic fasciitis. The patient had only limited improvement with steroids, methotrexate, mycophenolate mofetil, and intralesional triamcinolone acetonide injections.
CONCLUSION
Generalized morphea with concomitant EF indicates some degree of therapeutic resistance and poor prognosis with a low quality of life. Burn injuries can be a trigger factor for this overlap syndrome. Prompt identification of at-risk individuals and initiating aggressive management are necessary.
PubMed: 38774817
DOI: 10.1155/2024/3123953 -
The Pharmacogenomics Journal May 2024Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced...
Inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C (rs11706052) and 12-month evolution of the graft function in renal transplant recipients on mycophenolate-based immunosuppression.
Variant allele at the inosine monophosphate dehydrogenase type 2 polymorphism IMPDH2 3757T>C has been associated with increased enzyme activity and reduced susceptibility to mycophenolic acid (MPA) in vitro. It has been suggested associated with an increased risk of acute rejection in renal transplant recipients on MPA-based immunosuppression, but not unambiguously. We assessed one-year evolution of the estimated glomerular filtration rate (eGFR) in transplanted variant allele carriers and wild-type subjects, while controlling for a number of demographic, pharmacogenetic, (co)morbidity, and treatment baseline and time-varying covariates. The eGFR slopes to day 28 (GMR = 1.01, 95% CI 0.93-1.09), and between days 28 and 365 (GMR = 1.01, 95% CI 0.99-1.02) were practically identical in 52 variant carriers and 202 wild-type controls. The estimates (95%CIs) remained within the limits of ±20% difference even after adjustment for a strong hypothetical effect of unmeasured confounders. Polymorphism IMPDH2 3757T>C does not affect the renal graft function over the 1st year after transplantation.
Topics: Humans; Kidney Transplantation; IMP Dehydrogenase; Mycophenolic Acid; Male; Female; Middle Aged; Immunosuppressive Agents; Glomerular Filtration Rate; Adult; Graft Rejection; Polymorphism, Single Nucleotide; Aged; Immunosuppression Therapy
PubMed: 38769303
DOI: 10.1038/s41397-024-00335-0 -
Rheumatology International May 2024Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory... (Review)
Review
Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. A consistent feature of many cases is pulmonary infiltrates, or respiratory failure. This systematic literature review aims to summarise the pulmonary manifestations of IgG4-RD, including clinical outcomes and treatment. This review was registered on PROSPERO (CRD42023416410). Medline, Embase and Cochrane databases were searched for articles discussing IgG4-RD syndrome. Information was extracted on demographics, type and prevalence of pulmonary manifestations, treatment and clinical outcomes. Initially, after deduplication, 3123 articles were retrieved with 18 ultimately included. A pooled total of 724 patients with IgG4-RD were included, 68.6% male, mean age 59.4 years (SD 5.8) at disease onset. The most frequently described pulmonary manifestation was mediastinal lymphadenopathy (n = 186, 48.8%), followed by pulmonary nodules (n = 151, 39.6%) and broncho-vascular thickening (n = 85, 22.3%). Where treatment was reported, the majority of patients received glucocorticoids (n = 211, 93.4%). Other immunosuppressive therapy included cyclophosphamide (n = 31), azathioprine (n = 18), with mycophenolate mofetil (n = 6), rituximab (n = 6), methotrexate (n = 5) and other unspecified immunomodulators (50). Clinical outcomes were reported in 263 patients, where 196 patients had remission of their disease, 20 had relapse, 35 had stable disease, four had progression and eight patients died from complications of IgG4-RD. This systematic review summarises pulmonary manifestations, treatments and outcomes in patients with IgG4-RD. Pulmonary involvement in IgG4-RD is relatively common, leading to high levels of morbidity and mortality. Glucocorticoids remain the mainstay of treatment, but further work is required to explore the management of patients with pulmonary manifestations in association with IgG4-RD.
PubMed: 38769126
DOI: 10.1007/s00296-024-05611-7 -
Arthritis & Rheumatology (Hoboken, N.J.) May 2024Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN).
Impact of Glucocorticoid Dose on Complete Response, Serious Infections, and Mortality During the Initial Therapy of Lupus Nephritis: A Systematic Review and Meta-Analysis of the Control Arms of Randomized Controlled Trials.
OBJECTIVE
Our objective was to evaluate the effect of glucocorticoid regimens on renal response, infections, and mortality among patients with lupus nephritis (LN).
METHODS
We performed a systematic review and meta-analysis of the control arms of randomized clinical trials (RCTs). We included RCTs of biopsy-proven LN that used a protocolized regimen of glucocorticoids in combination with mycophenolic acid analogs or cyclophosphamide and reported the outcomes of complete response (CR), serious infections, and death. The starting dosage of glucocorticoids, tapering method, and administration of glucocorticoid pulses were abstracted. Meta-analysis of proportions, meta-regression, and subgroup meta-analysis were performed at 6 and 12 months for all outcomes.
RESULTS
Fifty RCT arms (3,231 patients with LN) were included. The predicted rates of CR, serious infections, and death when starting on oral prednisone at 25 mg/day without pulses were 19.5% (95% confidence interval [CI] 7.3-31.5), 3.2% (95% CI 2.4-4.0), and 0.2% (95% CI 0.0-0.4), respectively. Starting on prednisone at 60 mg/day (without pulses) increased the rates to 34.6% (95% CI 16.9-52.3), 12.1% (95% CI 9.3-14.9), and 2.7% (95% CI 0.0-5.3), respectively. Adding glucocorticoid pulses increased the rates of CR and death but not serious infections. We observed a dose-response gradient between the initial glucocorticoid dosage and all the outcomes at six months after accounting for the administration of glucocorticoid pulses, underlying immunosuppressant, and baseline proteinuria.
CONCLUSION
A higher exposure to glucocorticoids during the initial therapy of LN was associated with better renal outcomes at the cost of increased infections and death.
PubMed: 38766897
DOI: 10.1002/art.42920 -
Heart & Lung : the Journal of Critical... 2024COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment...
BACKGROUND
COVID patients continue to experience unremitting symptoms that extend far beyond the initial illness. While there is rapid accumulation of data on acute COVID treatment in hospitalized patients, little is known regarding post-COVID management.
OBJECTIVES
To describe our center's experience treating post-COVID sub-syndromes encountered in Post-COVID Lung Clinic.
METHODS
We retrospectively reviewed data on 98 post-COVID patients evaluated in our clinic between 07/01/2020-12/31/2022. We encountered three distinct post-COVID subtypes: 1) respiratory complaints associated with increased O2 requirements and abnormal CT findings (post-COVID interstitial lung disease [ILD]), 2) respiratory complaints associated with tachycardia (post-COVID dyspnea-tachycardia syndrome [DTS]). Post-COVID ILD patients (n = 28) received steroids in combination with cell cycle inhibitor (mycophenolate mofetil-MMF). Post-COVID DTS patients (n = 16) were treated with metoprolol. 3) A third, undifferentiated group presented with mild respiratory complaints and normal spirometry (n = 17) and was followed in clinic without initiation of a specific treatment.
RESULTS
In treated post-COVID ILD patients, mean oxygen requirements at rest (1.96 ± 1.79 L/NC) decreased to 0.89 ± 1.29 L/NC at 6 months follow-up, p = 0.005. In patients with post-COVID DTS, mean heart rate at rest decreased (98 ± 15 bpm to 79 ± 11 bpm) at 6 months follow-up, p = 0.023. 60 % of patients reported an improvement in exertional dyspnea.
CONCLUSIONS
Our descriptive study presents a single center outpatient COVID-19 clinic experience. We encountered 3 post-COVID sub-syndromes and describe their treatments: post-COVID interstitial lung disease [ILD] treated with a novel regimen of MMF and steroids, post COVID dyspnea-tachycardia syndrome [DTS] treated with metoprolol, and a third subgroup with mild undifferentiated symptoms without specific treatment.
Topics: Humans; COVID-19; Male; Female; Retrospective Studies; Middle Aged; Aged; Dyspnea; SARS-CoV-2; Lung Diseases, Interstitial; Ambulatory Care; Tachycardia; Post-Acute COVID-19 Syndrome; Metoprolol
PubMed: 38759575
DOI: 10.1016/j.hrtlng.2024.05.004 -
Frontiers in Medicine 2024Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation...
INTRODUCTION
Posterior reversible encephalopathy syndrome (PRES) is a serious neurological syndrome that may develop following immunosuppressive therapy for stem cell transplantation (SCT). We report 8 patients with sickle cell disease (SCD) who developed PRES, which is likely to be related to immunosuppression.
METHODS
This is retrospective cohort analysis of the SCD registry at the King Faisal Specialist Hospital and Research Center (KFSHRC) in Riyadh, Saudi Arabia. Inclusion criteria included all adults SCD patients who underwent SCT from 2011 until 2022. We explored all cases of PRES in patients with SCT. PRES was diagnosed with MRI imaging showing reversible vasogenic cerebral edema associated with neurological symptoms including severe headache, seizures, encephalopathy, delirium, and visual disturbances.
RESULTS
During ten years follow-up (2011-2022) we found 8 patients with PRES (age range between 14 to 37 years at diagnosis) PRES occurred 8 to 124 days following SCT in 7 cases and one patient developed PRES 8 months prior to SCT. All patients were on immunosuppressive medications, including tacrolimus, cyclosporine, sirolimus and or mycophenolate mofetil. Headache, seizures, visual hallucinations, confusion, and drowsiness were the most common presenting symptoms. MRI showed abnormalities in the occipital, parietal and frontal lobes in most cases. Recovery was complete in all patients and no recurrences were noted. Two patients had graft versus host disease (GVHD). We compared risk factors for PRES among the 8 cases and 136 SCT in SCD patients who did not develop PRES. There was a significant association between PRES and imaging abnormalities, including previous bi-hemispheric infarctions ( = 0.001), and cerebral microbleeds (CBMs). PRES was strongly associated with presence ( = 0.006), size ( = 0.016) and number ( = 0.005) of CMBs.
CONCLUSION
PRES can develop days to weeks following SCT in patients with SCD, and is associated with immunosuppressive therapy, previous bi-hemispheric infarctions and CMB. Prompt recognition and intervention leads to good recovery.
PubMed: 38751974
DOI: 10.3389/fmed.2024.1330688 -
JPMA. the Journal of the Pakistan... Apr 2024Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated,...
Endomyocardial fibrosis secondary to hyper-eosinophilic syndrome also known as Loeffler's Endocarditis is a rare cause of restrictive cardiomyopathy. If left untreated, it carries a very high morbidity and mortality rate. The case of a 20 years old girl, a known case of polyarticular juvenile idiopathic arthritis since the age of 13 years was reported at Federal Government Polyclinic Hospital, Islamabad on 14th May 2022. She presented with an acute history of shortness of breath and cough for two weeks. Her initial echocardiogram showed suspicion of Loeffler's Endocarditis, which is attributed to be an adverse effect of etanercept- a tumour necrosis factor (TNF) inhibitor, which she had been prescribed for her arthritis. The patient is currently being managed with high doses of steroids, therapeutic anticoagulation with rivaroxaban, carvedilol for tachycardia and mycophenolate mofetil as an immunosuppressant.
Topics: Humans; Female; Arthritis, Juvenile; Endomyocardial Fibrosis; Young Adult; Etanercept; Hypereosinophilic Syndrome; Echocardiography
PubMed: 38751280
DOI: 10.47391/JPMA.8648 -
Internal Medicine (Tokyo, Japan) May 2024A 59-year-old woman presented with a rash on the top part of her hands and pain in the wrist joint and was diagnosed with dermatomyositis complicated by interstitial...
Successful Treatment with Mycophenolate Mofetil in a Patieint with Anti-MDA 5 Antibody-positive Interstitial Lung Disease and Posterior Reversible Encephalopathy syndrome: A Case Report.
A 59-year-old woman presented with a rash on the top part of her hands and pain in the wrist joint and was diagnosed with dermatomyositis complicated by interstitial pneumonia positive for anti-melanoma differentiation-associated gene 5 (MDA-5) antibody. However, the patient reported a severe headache following treatment with oral prednisolone and tacrolimus. Posterior reversible encephalopathy syndrome (PRES) was diagnosed based on the brain magnetic resonance imaging findings. Tacrolimus was discontinued, and mycophenolate mofetil was instead administered with a favorable outcome. Mycophenolate mofetil should therefore be considered as an alternative treatment for anti-MDA-5-positive interstitial lung disease in cases where calcineurin inhibitors cannot be used.
PubMed: 38749731
DOI: 10.2169/internalmedicine.3533-24 -
BMJ Case Reports May 2024A woman in her 70s presented with anasarca and exertional dyspnoea. Investigation showed severe hypoalbuminaemia with no urinary or gastrointestinal protein losses. CT...
A woman in her 70s presented with anasarca and exertional dyspnoea. Investigation showed severe hypoalbuminaemia with no urinary or gastrointestinal protein losses. CT thorax reported lung consolidations, and transbronchial lung biopsy demonstrated organising pneumonia. Autoimmune myositis serology was positive for anti-Jo-1, anti-Ro-52, and anti-PM/Scl-100 antibodies. She was diagnosed with anti-synthetase syndrome with organising pneumonia. She was treated with oral prednisolone and oral mycophenolate mofetil with a good clinical response.
Topics: Humans; Female; Myositis; Aged; Edema; Prednisolone; Mycophenolic Acid; Tomography, X-Ray Computed; Pneumonia; Dyspnea
PubMed: 38749521
DOI: 10.1136/bcr-2023-258359