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BMJ Open Mar 2024Several studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission...
Enteric-coated Mycophenolate Sodium therApy versus cyclophosphamide for induction of Remission in Microscopic PolyAngiitis (EMSAR-MPA trial): study protocol for a randomised controlled trial.
INTRODUCTION
Several studies have demonstrated that mycophenolate mofetil (MMF) may be an excellent alternative to cyclophosphamide (CYC) or rituximab for the induction of remission in non-life-threatening anti-neutrophil cytoplasmic antibodies associated vasculitis because of its strong immunosuppressive potency and low toxicity profile. Enteric-coated mycophenolate sodium (EC-MPS) was introduced to reduce gastrointestinal adverse reactions of MMF. This study will evaluate the efficacy and safety of EC-MPS combined with glucocorticoid in patients with active and non-life-threatening microscopic polyangiitis (MPA).
METHODS AND ANALYSIS
This study is a multicentre, open-label, randomised controlled, non-inferiority trial. A total of 110 patients with active and non-life-threatening MPA from 11 hospitals in Shanxi Province of China will be recruited and randomised in a 1:1 ratio to receive either EC-MPS or CYC. All patients will receive the same glucocorticoid plan. We will compare oral EC-MPS (720-1440 mg/day) with intravenous pulsed CYC (7.5-15 mg/kg) administered for 3-6 months. All patients will be switched from their assigned treatment (EC-MPS or CYC) to oral azathioprine (2 mg/kg/day) after remission has been achieved, between 3 and 6 months. Azathioprine will be continued until the study ends at 18 months. The primary end point of efficacy is the remission rate at 6 months. Follow-up will continue for 18 months in order to detect an influence of induction regimen on subsequent relapse rates.
ETHICS AND DISSEMINATION
This study has received approval from the Ethics Committee of the Second Hospital of Shanxi Medical University (2022YX-026). All participants are required to provide written informed consent and no study-related procedures will be performed until consent is obtained. The results of this trial will be published in peer-reviewed journals and presented at conferences.
TRIAL REGISTRATION NUMBER
ChiCTR2200063823.
Topics: Humans; Azathioprine; Cyclophosphamide; Glucocorticoids; Immunosuppressive Agents; Microscopic Polyangiitis; Multicenter Studies as Topic; Mycophenolic Acid; Randomized Controlled Trials as Topic; Remission Induction; Equivalence Trials as Topic
PubMed: 38471694
DOI: 10.1136/bmjopen-2023-074662 -
Zhurnal Nevrologii I Psikhiatrii Imeni... 2024Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory...
OBJECTIVE
Analysis of demographic, clinical, laboratory, electrophysiological and neuroimaging data and pathogenetic therapy of pediatric patients with chronic inflammatory demyelinating polyneuropathy (CIDP).
MATERIAL AND METHODS
Patients (=30) were observed in a separate structural unit of the Russian Children's Clinical Hospital of the Russian National Research Medical University named after. N.I. Pirogova Ministry of Health of the Russian Federation in the period from 2006 to 2023. The examination was carried out in accordance with the recommendations of the Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society on the Management of CIDP (2021). All patients received immunotherapy, including intravenous immunoglobulin (IVIG) (=1), IVIG and glucocorticosteroids (GCS) (=17, 56.7%), IVIG+GCS+plasmapheresis (=12, 40.0%). Alternative therapy included cyclophosphamide (=1), cyclophosphamide followed by mycophenolate mofetil (=1), rituximab (=2, 6.6%), azathioprine (=3), mycophenolate mofetil (=2, 6.6%).
RESULTS
In all patients, there was a significant difference between scores on the MRCss and INCAT functional scales before and after treatment. At the moment, 11/30 (36.6%) patients are in clinical remission and are not receiving pathogenetic therapy. The median duration of remission is 48 months (30-84). The longest remission (84 months) was observed in a patient with the onset of CIDP at the age of 1 year 7 months.
CONCLUSION
Early diagnosis of CIDP is important, since the disease is potentially curable; early administration of pathogenetic therapy provides a long-term favorable prognosis.
Topics: Humans; Child; Infant; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Immunoglobulins, Intravenous; Mycophenolic Acid; Peripheral Nerves; Cyclophosphamide
PubMed: 38465811
DOI: 10.17116/jnevro202412402158 -
Infectious Diseases (London, England) May 2024Gastrointestinal complications are common in kidney transplant (KT) patients and can be a consequence of the chronic use of immunosuppression. The differential diagnosis...
BACKGROUND
Gastrointestinal complications are common in kidney transplant (KT) patients and can be a consequence of the chronic use of immunosuppression. The differential diagnosis of colitis in KT patients includes intolerance to immunosuppressive agents, namely mycophenolate mofetil, inflammatory bowel disease (IBD) and opportunistic infections. Epstein-Barr virus (EBV) infection may cause post-transplant colitis or trigger IBD, although is seldom thought as the causative pathogen.
OBJECTIVES
To describe clinical characteristics, endoscopic and histological findings, treatment and outcome of three patients that developed EBV associated colitis following kidney transplantation.
METHODS
We retrospectively analyzed three patients with EBV associated colitis; clinical data including transplantation, gastrointestinal symptoms, endoscopy findings, and follow-up data was obtained.
RESULTS
We present a case series of three patients with EBV colitis following KT, with an average age at clinical presentation of 59 years and elapsed time since the KT ranging from five to 22 years. Clinical manifestations included bloody diarrhoea, abdominal pain, weight loss and/or fever. Cytomegalovirus colitis, mycophenolate mofetil-related colitis, lymphoproliferative disease and graft versus host disease were excluded. One patient had a prior diagnosis of IBD. Two of the three patients had an unfavourable outcome with death despite reduction and/or switching of immunosuppressants, optimal medical treatment (including antiviral and intravenous immunoglobulin therapies) and salvage surgical therapy.
CONCLUSION
A multidisciplinary approach is necessary to allow an expeditious diagnosis of a rare entity such as EBV associated colitis in KT. Long-term surveillance of these patients and the development of effective and safe therapies is essential.
Topics: Humans; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Kidney Transplantation; Retrospective Studies; Mycophenolic Acid; Inflammatory Bowel Diseases; Immunosuppressive Agents; Colitis; Opportunistic Infections; Lymphoproliferative Disorders
PubMed: 38459811
DOI: 10.1080/23744235.2024.2326594 -
Journal of Hepatology Jul 2024
Comparative Study
Topics: Humans; Mycophenolic Acid; Hepatitis, Autoimmune; Azathioprine; Immunosuppressive Agents
PubMed: 38458322
DOI: 10.1016/j.jhep.2024.02.022 -
Narra J Dec 2023Polymyositis is a chronic autoimmune disease that presents with symmetrical progressive proximal muscle weakness. The cause of this disease due to abnormal activation of...
Polymyositis is a chronic autoimmune disease that presents with symmetrical progressive proximal muscle weakness. The cause of this disease due to abnormal activation of macrophages that might be associated with systemic diseases such as other autoimmune diseases, malignancy or viral infections including hepatitis B virus. The aim of this case report was to highlight treatment challenges in a patient with polymyositis concomitant with hepatitis B. A 28-years-old man with history of completed hepatitis B treatment with negative viral load presented with symmetrical progressive weakness on both inferior proximal extremities. The patient complained of pain predominantly in both tights and calves. No dermatological manifestation was observed. Elevated muscle enzymes and liver function were observed. Along with the course of the disease, hepatitis B reactivation was discovered as hepatitis B virus DNA was re-detected. Treatment options of this patient (polymyositis concomitant with hepatitis B viral infection) remain challenging. The main treatment of polymyositis consists of high dose methylprednisolone and this immunosuppressant could worsen the hepatitis B virus infection. The patient was finally treated with combination of mycophenolic acid and methylprednisolone for polymyositis and entecavir for hepatitis B. After one month of treatment, the patient showed a clinical improvement. This case highlights that viral screening must be done prior to starting polymyositis treatment as it could concomitant with viral infections such as hepatitis B. Antiviral prophylaxis must be given 1-2 weeks before immunosuppression starts. Management for both polymyositis and hepatitis B is important with entecavir or tenofovir as the optimal agents against hepatitis B virus.
PubMed: 38455623
DOI: 10.52225/narra.v3i3.514 -
Skin Research and Technology : Official... Mar 2024The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine,... (Review)
Review
AIMS AND OBJECTIVES
The purpose of this study is to investigate the effectiveness and safety of oral and injectable systemic treatments, such as methotrexate, azathioprine, cyclosporine, tofacitinib, baricitinib, corticosteroids, statins, zinc, apremilast, etc., for treating vitiligo lesions.
METHOD
Databases including PubMed, Scopus, and Web of Science were meticulously searched for studies spanning from 2010 to August 2023, focusing on systemic oral and injectable therapies for vitiligo, using comprehensive keywords and search syntaxes tailored to each database. Key data extracted included study design, treatment efficacy, patient outcomes, patient satisfaction, and safety profiles.
RESULTS
In a total of 42 included studies, oral mini-pulse corticosteroid therapy (OMP) was the subject of six studies (14.2%). Minocycline was the focus of five studies (11.9%), while methotrexate, apremilast, and tofacitinib each were examined in four studies (9.5%). Antioxidants and Afamelanotide were the subjects of three studies each (7.1%). Cyclosporine, simvastatin, oral zinc, oral corticosteroids (excluding OMP) and injections, and baricitinib were each explored in two studies (4.8%). Azathioprine, mycophenolate mofetil, and Alefacept were the subjects of one study each (2.4%).
CONCLUSION
Systemic treatments for vitiligo have been successful in controlling lesions without notable side effects. OMP, Methotrexate, Azathioprine, Cyclosporine, Mycophenolate mofetil, Simvastatin, Apremilast, Minocycline, Afamelanotide, Tofacitinib, Baricitinib, Antioxidants, and oral/injectable corticosteroids are effective treatment methods. However, oral zinc and alefacept did not show effectiveness.
Topics: Humans; Methotrexate; Azathioprine; Vitiligo; Mycophenolic Acid; Minocycline; Alefacept; Cyclosporine; Adrenal Cortex Hormones; Hypopigmentation; Simvastatin; Zinc; Purines; Pyrazoles; Sulfonamides; Azetidines; Thalidomide
PubMed: 38454597
DOI: 10.1111/srt.13642 -
The American Journal of Case Reports Mar 2024BACKGROUND The incidence of renal cell carcinoma (RCC) in transplanted kidneys is reported to be about 0.2%, which makes this case exceedingly rare. Risk factors include...
BACKGROUND The incidence of renal cell carcinoma (RCC) in transplanted kidneys is reported to be about 0.2%, which makes this case exceedingly rare. Risk factors include older age of the donors, smoking, obesity, and hypertension. Higher incidences of allograft RCC have been seen in patients who received a kidney from a deceased donor rather than from a living donor. CASE REPORT A 71-year-old woman with end-stage renal disease underwent deceased donor kidney transplantation (DDKT) 1 year before presentation. The immune-suppressive regimen was Envarsus, Myfortic, and prednisone. Allograft functioned with a baseline creatinine of 1.4-1.5 mg/dL. The patient presented due to recurring UTIs, which prompted the ultrasound that showed a mass on the allograft. Abdominal MRI demonstrated a 3.5-cm mass in the upper pole. Biopsy showed clear-cell RCC, Fuhrman nuclear grade 3. The patient underwent a partial nephrectomy. Following the nephrectomy, baseline serum creatinine was 1.7-2 mg/dL. The patient was discharged with immunosuppressive therapy consisting of Myfortic, prednisone, and Rapamune after diagnosis. CONCLUSIONS There are no standard treatment guidelines or optimal immune therapy for the management of allograft RCC in renal transplant recipients. Options include radical nephrectomy, nephron-sparing surgery (NSS), radiofrequency ablation (RFA), and active surveillance. According to a systematic review, the recurrence of cancer after partial nephrectomy was 3.6% after 3.1 years, which was similar to non-transplanted kidneys. There is not enough evidence to support screening for RCC in patients with transplanted kidneys, but constitutional symptoms like recurrent UTIs should prompt further investigation for potential malignancies in these patients.
Topics: Aged; Female; Humans; Carcinoma, Renal Cell; Creatinine; Kidney Neoplasms; Kidney Transplantation; Mycophenolic Acid; Prednisone
PubMed: 38442088
DOI: 10.12659/AJCR.941214 -
The Journal of Infection Mar 2024To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
To study the effect of mycophenolate mofetil (MMF) on various vaccination responses in kidney transplant recipients.
METHODS
In a randomized controlled trial (EudraCT nr.: 2014-001372-66), low immunologically risk kidney transplant recipients were randomized to TAC/MMF or TAC-monotherapy (TACmono), six months post-transplantation. One year after transplantation, in a pre-specified sub-study, recipients were vaccinated against pneumococcus, tetanus and influenza. Blood was sampled before and 21 days after vaccination. Adequate vaccination responses were defined by international criteria. A post-hoc analysis was conducted on SARS-CoV-2 vaccination responses within the same cohort.
RESULTS
Seventy-one recipients received pneumococcal and tetanus vaccines (TAC/MMF: n = 37, TACmono: n = 34), with 29 also vaccinated against influenza. When vaccinated, recipients were 60 (54-66) years old, with median eGFR of 54 (44-67) ml/min, tacrolimus trough levels 6.1 (5.4-7.0) ug/L in both groups and TAC/MMF daily MMF dose of 1000 (500-2000) mg. Adequate vaccination responses were: pneumococcal (TAC/MMF 43%, TACmono 74%, p = 0.016), tetanus (TAC/MMF 35%, TACmono 82%, p < 0.0001) and influenza (TAC/MMF 20%, TACmono 71%, p = 0.0092). Only 7% of TAC/MMF responded adequately to all three compared to 36% of TACmono (p = 0.080). Additionally, 40% of TAC/MMF responded inadequately to all three, whereas all TACmono patients responded adequately to at least one vaccination (p = 0.041). Lower SARS-CoV-2 vaccination antibody responses correlated with lower pneumococcal antibody vaccination responses (correlation coefficient: 0.41, p = 0.040).
CONCLUSIONS
MMF on top of tacrolimus severely hampers antibody responses to a broad range of vaccinations.
Topics: Humans; Middle Aged; Aged; Mycophenolic Acid; Tacrolimus; Immunosuppressive Agents; Kidney Transplantation; Influenza, Human; Antibody Formation; COVID-19 Vaccines; Tetanus
PubMed: 38432583
DOI: 10.1016/j.jinf.2024.106133 -
The FEBS Journal May 2024The essential yeast protein GPN-loop GTPase 1 (Npa3) plays a critical role in RNA polymerase II (RNAPII) assembly and subsequent nuclear import. We previously identified...
The essential yeast protein GPN-loop GTPase 1 (Npa3) plays a critical role in RNA polymerase II (RNAPII) assembly and subsequent nuclear import. We previously identified a synthetic lethal interaction between a mutant lacking the carboxy-terminal 106-amino acid tail of Npa3 (npa3ΔC) and a bud27Δ mutant. As the prefoldin-like Bud27 protein participates in ribosome biogenesis and translation, we hypothesized that Npa3 may also regulate these biological processes. We investigated this proposal by using Saccharomyces cerevisiae strains episomally expressing either wild-type Npa3 or hypomorphic mutants (Npa3ΔC, Npa3K16R, and Npa3G70A). The Npa3ΔC mutant fully supports RNAPII nuclear localization and activity. However, the Npa3K16R and Npa3G70A mutants only partially mediate RNAPII nuclear targeting and exhibit a higher reduction in Npa3 function. Cell proliferation in these strains displayed an increased sensitivity to protein synthesis inhibitors hygromycin B and geneticin/G418 (npa3G70A > npa3K16R > npa3ΔC > NPA3 cells) but not to transcriptional elongation inhibitors 6-azauracil, mycophenolic acid or 1,10-phenanthroline. In all three mutant strains, the increase in sensitivity to both aminoglycoside antibiotics was totally rescued by expressing NPA3. Protein synthesis, visualized by quantifying puromycin incorporation into nascent-polypeptide chains, was markedly more sensitive to hygromycin B inhibition in npa3ΔC, npa3K16R, and npa3G70A than NPA3 cells. Notably, high-copy expression of the TIF11 gene, that encodes the eukaryotic translation initiation factor 1A (eIF1A) protein, completely suppressed both phenotypes (of reduced basal cell growth and increased sensitivity to hygromycin B) in npa3ΔC cells but not npa3K16R or npa3G70A cells. We conclude that Npa3 plays a critical RNAPII-independent and previously unrecognized role in translation initiation.
Topics: Hygromycin B; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; RNA Polymerase II; Protein Synthesis Inhibitors; GTP Phosphohydrolases; Cell Nucleus; Protein Biosynthesis
PubMed: 38431777
DOI: 10.1111/febs.17106 -
Journal Der Deutschen Dermatologischen... Apr 2024The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending...
The updated S2k guideline deals with the diagnosis and therapy of localized scleroderma (LoS). LoS represents a spectrum of sclerotic skin diseases in which, depending on the subtype and localisation, structures such as adipose tissue, muscles, joints, and bones may also be affected. Involvement of internal organs or progression to systemic sclerosis does not occur. LoS can be classified into four main forms: limited, generalized, linear, and mixed forms, with some additional subtypes. For cases of limited skin involvement, the guideline primarily recommends therapy with topical corticosteroids. UV therapy can also be recommended. In subtypes with severe skin or musculoskeletal involvement, systemic therapy with methotrexate is recommended. During the active phase of the disease, systemic glucocorticosteroids can be used additionally. In cases of methotrexate and steroid refractory courses, contraindications, or intolerance, mycophenolate mofetil, mycophenolic acid, or abatacept can be considered as second-line systemic therapies. In the case of linear LoS, autologous adipose-derived stem cell transplantation can also be performed for correcting soft tissue defects.
Topics: Humans; Methotrexate; Scleroderma, Localized; Skin; Dermatologic Agents; Mycophenolic Acid
PubMed: 38426689
DOI: 10.1111/ddg.15328