COVID-19 and renal allograft rejection: insight from controlled and non-controlled studies.

AIM: Kidney transplant recipients (KTRs), due to their immunosuppressed status, are potentially more susceptible to both the severe effects of COVID-19 and complications in their transplanted organ. The aim of this study is to investigate whether COVID-19 infection increases the risk of rejection in kidney transplant recipients (KTRs). METHODS: This study involved a detailed literature review, conducted using PubMed, with the search being completed by September 7th, 2023. The search strategy incorporated a combination of relevant keywords: 'COVID', 'Renal', 'Kidney', 'Transplant', and 'Rejection'. The results from controlled and uncontrolled studies were separately collated and analyzed. RESULTS: A total of 11 studies were identified, encompassing 1,179 patients. Among these, two controlled studies reported the incidence of rejection in KTRs infected with COVID-19. Pooling data from these studies revealed no significant statistical correlation between COVID-19 infection and biopsy-proven rejection (p = 0.26). In addition, nine non-controlled studies were found, with rejection incidences ranging from 0% to 66.7%. The majority of these studies (eight out of nine) had small sample sizes, ranging from 3 to 75 KTRs, while the largest included 372 KTRs. The combined rejection rate across these studies was calculated to be 11.8%. CONCLUSION: In conclusion, the limited number of published controlled studies revealed no statistically significant association between COVID-19 infection and biopsy-proven rejection among KTRs. However, the broader analysis of non-controlled studies showed a variable rejection incidence with a pooled rejection rate of 11.8%. There is insufficient high-quality data to explore the association of COVID-19 infection and rejection.

[Steroid-Dependent Nephrotic Syndrome Due to Minimal Change Glomerulonephritis Treated with Rituximab].

47-year-old woman suffering from minimal lesion glomerulonephritis previously undergone high-dose steroid therapy and subjected to exacerbations of nephrotic syndrome after therapy discontinuation. It was decided to initiate off-label treatment with Rituximab at a dosage of 375 mg/m2 administred at zero-time, one-month and three months with good therapeutic response and resolution of the clinical laboratory picture. The therapy was well tolerated and had no side effects. This scheme could be an alternative to the conventional therapeutic scheme with steroids or other classes of immunosuppressive drugs, especially in order to avoid problems related to prolonged exposure to steroid therapy.

Expression of Rejection-Associated Transcripts in Early Protocol Renal Transplant Biopsies Is Associated with Tacrolimus Exposure and Graft Outcome.

Subclinical inflammation in protocol biopsies relates to tacrolimus exposure and human leukocyte antigen (HLA) matching. We aimed to characterize transcripts associated with rejection and tacrolimus exposure and the latter's association with transplant outcomes. We tested whether gene expression is associated with rejection using strictly normal protocol biopsies (n = 17) and biopsies with T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR) according to Banff criteria (n = 12). Subsequently, we analyzed these transcripts in a set of 4-month protocol biopsies (n = 137) to assess their association with donor and recipient characteristics, the intensity of immunosuppression, and the graft outcome. Differential expression (false discovery rate (FDR) < 0.01, fold (change (FC) > 3) between normal and rejection biopsies yielded a set of 111 genes. In the protocol biopsy cohort (n = 137), 19 out of these 111 genes correlated with tacrolimus trough levels at the time of biopsy (TAC-C0), and unsupervised analysis split this cohort into two clusters. The two clusters differed in donor age and tacrolimus trough levels. Subclinical rejection, including borderline lesions, tended to occur in the same cluster. Logistic regression analysis indicated that TAC-C0 at the time of biopsy (OR: 0.83, 95%CI:0.72-0.06, p = 0.0117) was associated with cluster 2. In a follow-up averaging 70 ± 30 months, this patient group displayed a significant decline in renal function (p = 0.0135). The expression of rejection-associated transcripts in early protocol biopsies is associated with tacrolimus exposure and a faster decline in renal function.

Safety and efficacy of eltrombopag in patients with aplastic anemia: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This article conducts a systematic review of eltrombopag combined with immunosuppressive therapy for the treatment of aplastic anemia (AA), to demonstrate the effectiveness and safety of eltrombopag. METHODS: PubMed, Cochrane Library, Embase, OVID, Web of Science, China National Knowledge Infrastructure, and Wanfang databases were searched. Studies that met the inclusion criteria were collected, ranging from the establishment of the database to August 2023. Two reviewers performed meta-analyses using the Cochrane systematic review method and RevMan 5.3 software. RESULTS: This meta-analysis enrolled 5 studies with a total of 542 AA patients, including 274 in the experimental group and 268 in the control group. Meta-analyses were performed for efficacy and adverse reactions. The endpoint of effects included 6-month complete response (CR), 6-month partial response (PR), and 6-month overall response (OR). Eltrombopag combined with immunotherapy showed significant improvements in 6-month CR (OR: 2.20; 95% CI;1.54-3.12; P < 0.0001) and 6-month OR (OR = 3.66, 95% CI 2.39-5.61, P < 0.001)compared to immunosuppressive therapy for AA patients. In terms of safety, eltrombopag combined with immunosuppressive therapy showed significantly increased pigment deposition and abnormal liver function compared to immunosuppressive therapy alone. CONCLUSION: Compared to immunosuppressive therapy alone, eltrombopag combined with immunosuppressive therapy showed significant improvements in 6-month CR and 6-month OR. However, it also resulted in increased pigment deposition and abnormal liver function in terms of safety.

Initiation of belimumab with higher daily prednisolone is effective for rapid glucocorticoid reduction: A 96-week retrospective study.

OBJECTIVES: For appropriate glucocorticoid (GC) reduction, we investigated the optimal strategy including baseline factors that could reduce GC more than 50% with 96 weeks of belimumab. METHODS: This is a retrospective cohort study of Kakogawa Central City hospital from 2019 to 2023. We identified SLE patients who were receiving 200 mg of belimumab weekly by subcutaneous injection for 96 weeks. The background at baseline, trends in clinical indicators, and factors involved in GC reduction were statistically analyzed. Finally, univariate and multivariate logistic analyses were carried out to identify baseline factors associated ≥50% GC reduction at 96 weeks. RESULTS: Forty-seven patients were enrolled, with a median daily prednisolone of 5 mg. Almost 90% of them received concomitant immunosuppressants and/or hydroxychloroquine. Serological indices, daily GC dose, and SLEDAI-2K scores showed significant improvement in 96 weeks. At baseline, a significant negative correlation has been shown between the daily dose of GC and the duration from onset or last flare, as well as C4 levels. At 96 weeks, GC reduction rate and SLEDAI-2K scores were negatively correlated with duration from onset or last flare to initiation of belimumab. Mycophenolate mofetil use was significantly frequent in patients with lupus nephritis (LN), which also correlated with the frequency of past flares. In addition, LN presence was associated with higher SLEDAI-2K scores at 96 weeks, and baseline SLEDAI-2K ≥10 was associated with significantly higher GC dose at 96 weeks. Univariate analysis of the factor contributing to achieving ≥50% GC reduction at 96 weeks has pointed shorter disease duration and higher daily GC dose at baseline as significant variables. Finally, we performed a multivariate analysis by combining above two items with age, which extracted the higher daily GC dose at baseline as a significant variable (OR (95% CI) 1.25 (1.00 to 1.56), p = .047). CONCLUSIONS: Our study showed that a delay in belimumab initiation led to higher SLEDAI-2K score and difficulty in achieving a 50% GC reduction at 96 weeks. Since GC-related adverse events increase with long-term administration of GC though with small daily doses, we proposed here that belimumab should be started in combination with higher daily prednisolone.

The use of belimumab on patients with both systemic lupus erythematosus and immune thrombocytopenia: A retrospective cohort study.

OBJECTIVE: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. METHODS: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. RESULTS: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p < .05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p < .05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p > .05). CONCLUSION: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation.

[Comorbidities in multiple sclerosis and their influence on the choice of treatment]. / Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.

Clinical trials of disease-modifying therapies (DMTs) for people with multiple sclerosis (pMS) are conducted in selected populations, excluding patients with comorbidities or concomitant medications. However, a large percentage of pMS have some additional disease, which could affect the response and choice of the DMT. The objective of this review is to assess how concurrent pathologies can impact the choice of DMTs. Relevant articles were selected through a systematic search in PubMed. Comorbidities were grouped for better classification into autoimmune, chronic infections, cardiovascular and metabolic, oncological and neuropsychiatric. In autoimmune pathologies, it is key to take into account the effects of TME on them and the possibility of interaction with their specific treatments. Immunomodulatory therapies are safe for people with chronic infections. Immunosuppressive treatments are generally contraindicated in people with active infections. In cardiovascular and metabolic comorbidities, infusion reactions associated with monoclonal antibodies, and the phenomena of starting treatment with S1P modulators, must be taken into account. DMTs with an immunosuppressive effect are contraindicated in people with active malignancies. Although psychiatric pathology per se does not preclude the use of DMTs, caution should be exercised when new psychiatric symptoms appear. For these reasons, among the multiple factors that must be considered when starting or changing a DMT in pMS, comorbidities constitute a decisive element.

TITLE: Comorbilidades en la esclerosis múltiple y su influencia en la elección del tratamiento.Los estudios clínicos de tratamientos para personas con esclerosis múltiple (pEM) se realizan en poblaciones seleccionadas, que excluyen a pacientes que presenten comorbilidades o medicaciones concomitantes. Sin embargo, un gran porcentaje de las pEM tiene alguna enfermedad adicional, que podría afectar a la respuesta y la elección del tratamiento. El objetivo de esta revisión es valorar cómo pueden las diferentes patologías concurrentes impactar en la elección de las terapias modificadoras de la enfermedad (TME) en las pEM. Se seleccionaron artículos relevantes mediante búsqueda en PubMed. Las comorbilidades se agruparon, a los fines de mejor ordenamiento de los artículos encontrados, en patologías diversas: autoinmunes, infecciones crónicas, cardiovasculares, respiratorias, metabólicas, oncológicas, neuropsiquiátricas y epilepsia. En cuanto a las patologías autoinmunes, es clave tener en cuenta los efectos de las TME sobre ellas y la posibilidad de interacción con sus tratamientos específicos. Las terapias inmunomoduladoras son seguras para personas con infecciones crónicas. Los tratamientos inmunosupresores, en general, están contraindicados en personas con infecciones activas. En las comorbilidades cardiovasculares y metabólicas deben tenerse en cuenta las potenciales reacciones de infusión asociadas a anticuerpos monoclonales, y los fenómenos asociados al inicio de tratamiento con moduladores del receptor de la esfingosina-1-fosfato. Las TME con efecto inmunosupresor están contraindicadas en personas con malignidades activas. Aunque la patología psiquiátrica de por sí no impide el uso de TME, debería tenerse precaución cuando aparecen nuevos síntomas psiquiátricos, y siempre tenerse en cuenta su monitorización y tratamiento. Por este motivo, entre los múltiples factores que deben considerarse a la hora de iniciar o cambiar una TME en pEM, las comorbilidades constituyen un elemento muchas veces decisivo.

Efficacy and safety of low-dose corticosteroids combined with leflunomide for progressive IgA nephropathy: a systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The effectiveness of immunosuppressive and corticosteroid treatments for Immunoglobulin A (IgA) nephropathy (IgAN) remains thoroughly evaluated. We undertook a meta-analysis to investigate the efficacy and safety of low-dose corticosteroids plus leflunomide for progressive IgA nephropathy. METHODS: Eligible studies were obtained from PubMed, Embase, and Cochrane Library databases. We also searched the references of the included studies. Our protocol followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) checklist. Eligibility criteria were defined using a PICOS framework. RESULTS: Our study included three articles presenting 342 patient cases. Findings revealed that low-dose corticosteroids combined with the leflunomide group were effective in relieving urine protein excretion (UPE) [mean difference (MD) = -0.35, 95% confidence interval (CI): -0.41 to -0.30, P < 0.00001] compared with the full-dose corticosteroids group. Regarding serum creatinine (SCr), estimated glomerular filtration rate (eGFR), complete remission rate, and overall response rate, there was no difference between the groups (p > 0.05). Regarding safety, low-dose corticosteroids combined with leflunomide significantly reduced the risk of serious adverse events [odds ratio (OR): 0.11, 95% CI: 0.01 to 0.91, P = 0.04]. Besides, no significant differences were observed between the two groups in the incidence of respiratory infection, abnormal liver function, diarrhea, herpes zoster, alopecia, pruritus, insomnia, pneumonia, diabetes, and urinary tract infection (P > 0.05). CONCLUSIONS: Low-dose corticosteroids combined with leflunomide are a safe and effective treatment for progressive IgA nephropathy. TRIAL REGISTRATION: The PROSPERO registration number is CRD42022361883.

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.

Efficacy and safety of Mahuang Fuzi and Shenzhuo Decoction for treatment of primary membranous nephropathy: a multicenter prospective trial.

BACKGROUND: This study aims to undertake a comprehensive assessment of the effectiveness and safety profile of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in the management of primary membranous nephropathy (PMN), within the context of a prospective clinical investigation. METHODS: A multicenter, open-label clinical trial was executed on patients diagnosed with PMN. These individuals were subjected to MFSD therapy for a duration of at least 24 months, with primary outcome of clinical remission rates. The Cox regression analysis was employed to discern the pertinent risk factors exerting influence on the efficacy of MFSD treatment, with scrupulous monitoring of any adverse events. RESULTS: The study comprised 198 participants in total. Following 24 months of treatment, the remission rate was 58.6% (116/198). Among the subgroup of 130 participants subjected to a 36-month follow-up, the remission rate reached 70% (91/130). Subgroup analysis revealed that neither a history of immunosuppressive therapy (HIST) nor an age threshold of ≥60 years exhibited a statistically significant impact on the remission rate at the 24-month mark (p > .05). Multivariate Cox regression analyses elucidated HIST, nephrotic syndrome, or mass proteinuria, and a high-risk classification as noteworthy risk factors in the context of MFSD treatment. Remarkably, no fatalities resulting from side effects were documented throughout the study's duration. CONCLUSIONS: This trial establishes the efficacy of MFSD as a treatment modality for membranous nephropathy. MFSD demonstrates a favorable side effect profile, and remission rates are consistent across patients, irrespective of HIST and age categories.

Treatment of plaque-psoriasis in HIV-positive patients.

Psoriasis is a chronic inflammatory disease that can often accompany human immunodeficiency virus (HIV) epidemics. Development of psoriasis in HIV patients is correlated with a decrease in CD4+ count. Significant variability in the clinical presentation of psoriasis makes it a challenging disease to diagnose. Furthermore, associated immunodeficiency complicates standard treatment with immunosuppressive and biological therapy. Articles that match the terms psoriasis and HIV were searched in MEDLINE and Embase and selected based on their relevance. Highly active antiretroviral therapy (HAART) is a medication regimen used to manage and treat HIV infection. In treating mild psoriasis in HIV-positive patients, topical agents combined with HAART are considered first-line therapy, followed by phototherapy. Second-line therapy includes oral retinoids, alone or combined. In treating challenging cases, apremilast has been used due to its lack of immunosuppressive effect. In case of progressive and refractory disease, limited data from studies suggest that immunosuppressive or biological therapy may be effective. Treatment of psoriasis in HIV patients remains a challenge, which is largely attributable to its complicated etiopathology and lack of an approved therapy option. In treating severe psoriasis, close collaboration with an infectious disease specialist is highly recommended. Further research is needed, preferably with an aim toward developing individualized therapy.

Early neonatal outcomes in infants of mothers with organ transplantation under immunosuppressive treatment.

BACKGROUND: This study aimed to examine early clinical and laboratory findings in infants born to mothers who had organ transplants and received immunosuppressive treatment. METHODS: Between 2016 and 2023, the study examined infants of mothers who underwent organ transplantation and were receiving immunosuppressive treatment, and followed at the Department of Neonatology at Akdeniz University. Demographic, clinical, and laboratory characteristics of mothers and infants were recorded. On the first day of life, complete blood count values were examined, as well as potassium levels on the first, third, and seventh days, and creatinine levels on the third and seventh days. The tacrolimus blood level was calculated by taking the average of the tacrolimus blood values of the mother measured during the pregnancy. The infants were evaluated for any potential morbidities caused by intrauterine immunosuppressive drug exposure. RESULTS: The study included 21 mothers (some with multiple pregnancies) and 27 infants. According to the findings of this study, 74% of these infants were born premature, 67% had low birth weight, and all were delivered via cesarean section. Prematurity was associated with the morbidities found in the infants. In the early period, lymphopenia was detected in 37%, neutropenia in 25.9%, thrombocytopenia in 11.1%, hyperkalemia in 18.5%, and creatinine elevation in 7.4%, all of which returned to normal within a few days. There was no significant relationship between maternal tacrolimus blood levels and infant potassium and creatinine levels. CONCLUSION: Apart from an increased risk of prematurity, low birth weight, and cesarean delivery, no effects were observed in these infants during the early period. However, long-term follow-up is necessary to monitor for any potential morbidities.

Pharmacogenomic implications of the differential distribution of CYP3A5 metabolic phenotypes among Latin American populations.

This study shows that the distribution of CYP3A5 alleles (*1, *3, *6 and *7) and genotype-predicted CYP3A5 phenotypes vary significantly across Latin American cohorts (Brazilians and the One Thousand Genomes Admixed American superpopulation), as well as among subcohorts comprising individuals with the highest proportions of Native, European or sub-Saharan African ancestry. Differences in biogeographical ancestry across the study groups are the likely explanation for these results. The differential distribution of CYP3A5 phenotypes has major pharmacogenomic implications, affecting the proportion of individuals carrying high risk CYP3A5 phenotypes for the immunosuppressant tacrolimus and the number of patients that would need to be genotyped to prevent acute rejection in kidney transplant recipients under tacrolimus treatment.

Global tuberculosis disease and infection in systemic lupus erythematosus patients: A systematic review and meta-analysis.

BACKGROUND: Tuberculosis (TB) is one of the most common infections among systemic lupus erythematosus (SLE) patients. We aimed to evaluate the global prevalence of TB infection and disease, its type, and medication risk factors in SLE patients. METHODS: We searched PubMed, Science Direct, EBSCO, and Web of Science databases from inception to April 30, 2023, and included studies assessing TB among SLE patients. We estimated the prevalence of TB disease (including type of TB disease), TB infection, and SLE medication as TB risk factors. Meta-analysis was performed using Stata 14.2 and Review Manager 5.3. RESULTS: Twenty-seven studies met the eligibility criteria. The global prevalence of TB disease was 4% (95% confidence interval (CI): 3-4%, n = 25) and TB infection was 18% (95% CI: 10-26%, n = 3). The pooled prevalence of pulmonary TB, extrapulmonary TB, and disseminated TB were 2% (95% CI: 2-3%, n = 20), 1% (95% CI: 1-2%, n = 17), and 1% (95% CI: 0-1%, n = 6), respectively. The 1-year cumulative glucocorticoid (GC) dose in SLE patients contracting TB was higher than in those without TB, having a mean difference of 2.56 (95% CI: 0.22-4.91, p < .00001, n = 3). The odd ratio of TB was 2.11 (95% CI: 1.01-4.41, p = .05, n = 3) in SLE patients receiving methylprednisolone (MP) pulse therapy as compared to those without MP pulse therapy. Other immunosuppressive agents were not significantly associated with TB. CONCLUSION: TB prevalence in SLE was relatively high and associated with GC. Awareness of TB and lowering GC dose are warranted to alleviate the TB burden in SLE.

Nicolau syndrome following glatiramer acetate for multiple sclerosis: Case and review of reports.

Nicolau syndrome is a rare, iatrogenic skin reaction after parental drug administration, characterized by severe pain at an injection site, followed by hemorrhage, ulceration, and often necrosis. We present a case of a patient on glatiramer acetate for many years (initially Copaxone then Glatopa) who developed Nicolau syndrome, the second reported case after generic glatiramer acetate. All reported cases of Nicolau syndrome after glatiramer acetate are reviewed. The case highlights the importance of prompt recognition of this skin reaction by neurologists and raises awareness of the risks of skin reactions even in low-risk injectable DMTs.

Epstein-Barr virus associated colitis in kidney transplant patients: a case series.

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, de novo inflammatory bowel disease (IBD) and opportunistic infections. Epstein-Barr virus (EBV) infection may cause post-transplant colitis or trigger de novo 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.

Cytokine release syndrome caused by antineoplastic treatment with CAR-T and T-cell engaging therapies.

T-cell-based immunotherapy has recently evolved as a treatment option for a number of haematological malignancies and is also being developed in solid tumours. A common side effect of chimeric antigen T-cell therapy (CAR-T) and treatment with T-cell engagers is cytokine release syndrome (CRS), which is a potentially life-threatening condition characterized by release of inflammatory mediators. The treatment of CRS is similar to that of other hyper-inflammatory conditions and involves supportive treatment as well as immunosuppressive therapy. The risk of CRS can be mitigated by step-up dosing and immunosuppressive pre-treatment, as argued in this review.

Post-transplant lymphoproliferative disorders following kidney transplantation: A literature review with updates on risk factors, prognostic indices, screening strategies, treatment and analysis of donor type.

Post-transplant lymphoproliferative disorders (PTLD) is a devastating complication of kidney transplantation with an insidious presentation and potential to disseminate aggressively. This review delineates the risk factors, prognostic indexes, screening, current management algorithm and promising treatment strategies for PTLD. Kidneys from both extended criteria donors (ECD) and living donors (LD) are being increasingly used to expand the donor pool. This review also delineates whether PTLD outcomes vary based on these donor sources. While Epstein-Barr virus (EBV) is a well-known risk factor for PTLD development, the use of T-cell depleting induction agents has been increasingly implicated in aggressive, monomorphic forms of PTLD. Research regarding maintenance therapy is sparse. The international prognostic index seems to be the most validate prognostic tool. Screening for PTLD is controversial, as annual PET-CT is most sensitive but costly, while targeted monitoring of EBV-seronegative patients was more economically feasible, is recommended by the American Society of Transplantation, but is limited to a subset of the population. Other screening strategies such as using Immunoglobulin/T-cell receptor require further validation. A risk-stratified approach is taken in the treatment of PTLD. The first step is the reduction of immunosuppressants, after which rituximab and chemotherapy may be introduced if unsuccessful. Some novel treatments have also shown potential benefit in studies: brentuximab vedotin, chimeric antigen receptor T-cell therapy and EBV-specific cytotoxic T lymphocytes. Analysis of LD v DD recipients show no significant difference in incidence and mortality of PTLD but did reveal a shortened time to development of PTLD from transplant. Analysis of SCD vs ECD recipients show a higher incidence of PTLD in the ECD group, which might be attributed to longer time on dialysis for these patients, age, and the pro-inflammatory nature of these organs. However, incidence of PTLD overall is still extremely low. Efforts should be focused on optimising recipients instead. Minimising the use of T-cell depleting therapy while encouraging research on the effect of new immunosuppressants on PTLD, screening for EBV status are essential, while enabling shared decision-making during counselling when choosing kidney donor types and individualised risk tailoring are strongly advocated.

Data mining and safety analysis of traditional immunosuppressive drugs: a pharmacovigilance investigation based on the FAERS database.

OBJECTIVE: The purpose of this study aimed to explore the new and serious adverse events(AEs) of Tacrolimus(FK506), cyclosporine(CsA), azathioprine(AZA), mycophenolate mofetil(MMF), cyclophosphamide(CTX) and methotrexate(MTX), which have not been concerned. METHODS: The FAERS data from January 2016 and December 2022 were selected for disproportionality analysis to discover the potential risks of traditional immunosuppressive drugs. RESULTS: Compared with CsA, FK506 has more frequent transplant rejection, and is more related to renal impairment, COVID-19, cytomegalovirus infection and aspergillus infection. However, CsA has a high infection-related fatality rate. In addition, we also found some serious and rare AE in other drugs which were rarely reported in previous studies. For example, AZA is closely related to hepatosplenic T-cell lymphoma with high fatality rate and MTX is strongly related to hypofibrinogenemia. CONCLUSION: The AEs report on this study confirmed that the results were basically consistent with the previous studies, but there were also some important safety signals that were inconsistent with or not mentioned in previous published studies. EXPERT OPINION: The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to improve the safety of immunosuppressive drugs.

Retrospective analysis on incidence and risk factors of post-transplant diabetes mellitus after lung transplantation and its association with clinical outcomes.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) is a common complication after transplantation. We aim to explore potential risk factors of PTDM and its association with outcomes after lung transplantation (LTx). METHODS: A retrospective study was conducted in 100 patients who underwent LTx at our institution from 2017 to 2021. Patients' information was collected, and genotyping for single nucleotide polymorphisms known to potentially increase the risk of Type 2 DM was performed. Univariate and multivariate analyses were conducted to identify risk factors for PTDM. The primary outcome was the incidence of PTDM. Secondary outcomes were associations between PTDM and clinical outcomes following LTx. RESULTS: Thirty-nine patients (39.0%) developed PTDM, while 10 patients (25.6%) recovered subsequently. The incidence of PTDM was associated with age > 45 (HR: 2.919, 95% CI [1.021-8.348]), pre-transplant HbA1c > 5.7% (HR: 2.344, 95% CI [1.201-4.573]), KCNJ11 rs5215 (HR: 2.090, 95% CI [1.050-4.162]) and tacrolimus concentration > 8 ng/mL in the first month (HR: 2.090, 95% CI [1.050-4.162]). Patients with PTDM experienced elevated fasting blood glucose levels (FBG) during the first month post-transplantation (p < 0.001), and required a longer duration for FBG to return to normal levels (p < 0.001). However, the presence of PTDM did not significantly impact renal function, incidence of infection episodes, chronic lung allograft dysfunction or mortality following LTx. CONCLUSION: Advanced age, elevated HbA1c levels, KCNJ11 gene polymorphism, and early exposure to tacrolimus are all significant risk factors for PTDM following LTx. The clinical implications of these factors warrant attention.