Immunosuppressive Medications Research Articles

Combined [18F]-FDG PET-MR Imaging: A promising tool for diagnostics of small bowel Crohn's disease.

Introduction Diagnostics of small bowel Crohn's disease (CD) can be difficult. Combined positron emission tomography-magnetic resonance enterography (PET-MRE) can be used to evaluate intestinal metabolism, but clinical use has been limited due to accessibility, costs, absence of standardized methods and diagnostic thresholds. Our aim was to show that combined PET-MRE can be used to diagnose active small bowel CD. Methods We performed a fusion PET-MRE-scan with [18F]-FDG-tracer to 30 patients with suspected small bowel CD in colonoscopy. Standardized uptake values (SUV) were measured from small bowel. The diagnosis was confirmed with small bowel capsule endoscopy. Clinicians chose appropriate medication to each patient blinded from SUV-results. Endoscopic, laboratory and MRE-findings were investigated in relation to SUV. Results Fusion PET-MRE outperformed MRE in diagnostic accuracy. Patients diagnosed with CD (N=24) had higher SUV than patients not diagnosed with CD (N=6) (3.34 vs. 1.84, p=0.022). A diagnostic cut-off at SUV at 2.5. could be used (AUROC=0.81). A higher SUV predicts need for immunosuppressive medication (p=0.0026) and biologics (p=0.0005). SUV correlates positively with SES-CD-score (Simple Endoscopic Score for Crohn's Disease), fecal calprotectin and CRP and negatively with Hb and serum albumin. Conclusion In future, [18F]-FDG PET-MRE can be used in diagnostics of small bowel CD as a safe alternative for capsule endoscopy. High SUV can predict a more progressive disease course and need for more advanced therapies.

Abstract 4140138: Coronary Artery Vasculopathy in a Cohort of 321 Heart Transplant Recipients: A Single Center Experience

Introduction: Despite advances in surgical techniques, organ preservation methods and immunosuppressant medications, the ten-year survival for orthotropic heart transplantation (OHT) remains around 50%. Coronary artery vasculopathy (CAV), among other factors, seems to have an important role in accelerated organ injury and failure. Aim: To determine the rate of survival and CAV development along with associated factors in a cohort of OHT recipients. Methods: Patients who underwent OHT at Virginia Commonwealth University (VCU) between October 2008 and September 2021 were retrospectively reviewed until June 2024. According to the VCU protocol, right heart biopsies were done weekly for the first month, every other week for the second month and at the first year mark post transplant. Left heart catheterizations were done one year after OHT and then at 2 year intervals. Survival, CAV development and need for percutaneous coronary interventions (PCI) as well as organ rejection rates in CAV patients were surveyed. Results: A total of 321 patients received OHT during that period with a median follow up time of 8.15 years from the date of transplant. Of these, 122 patients had 10-year follow up or more post OHT (53.27% survived) and 240 patients had 5-year follow up or more (66.25% survived). All patients had greater than 2.75 years of follow up. The overall mortality was 29.5%. CAV occurred in 55 patients out of 321 (17%) with median time of 2.82 years for CAV development. Mortality in the CAV group was 40% compared to 27% in the non-CAV group. Out of 55 patients with CAV, 19 required at least 1 PCI with 3 requiring interventions on chronic total occlusions. Evidence of rejection on right ventricle biopsy was observed in 51% of patients with CAV Conclusion: Our cohort had above average 10-year survival rate compared to the national data. Results revealed CAV is common post OHT and has implications on long term survival. Given CAV may develop in the absence of organ rejection, further studies are needed to identify factors associated with CAV and explore optimal treatment options that would potentially improve long-term survival post OHT.

Abstract 4112639: A Rare Case of Atypical Sarcoidosis Presenting as an Intra-Atrial Septal Mass

Introduction: Sarcoidosis is a granulomatous disease that can affect multiple organ systems, including the heart. Cardiac Sarcoidosis (CS) is one of the most severe manifestations. It is characterized by a dysregulated T-cell driven immune response which generates non-necrotic inflammatory granulomas with myocardial infiltration. CS has a range of clinical syndromes: impaired conduction, arrhythmias, heart failure, and sudden cardiac death. We discuss a rare presentation of CS as an intra-atrial septal mass. Case Description: A 27-year-old Caucasian female with history of depression on citalopram presented with a one-month history of palpitations, fatigue, and dyspnea with exertion. An EKG demonstrated sinus rhythm with first-degree AV block. A cardiac monitor revealed intermittent 2-1 AV block and high degree AV block occurring mostly during sleep. An echocardiogram revealed normal biventricular function and morphology. Due to the concern for infiltrative cardiomyopathy, she underwent a cMRI which revealed a focal mass centered along the intra-atrial septum extending from the fossa ovalis to the septal AV junction, measuring 4.5 cm in size. She underwent pacemaker implantation with mild improvement of symptoms. PET scan demonstrated hypermetabolic activity of the intra-atrial region. She underwent surgical resection of the cardiac mass. Pathology was significant for fibrotic tissue with non-caseating granuloma and multinucleated giant cells consistent with an extremely rare presentation of CS. She was started on immunosuppressive medications. Subsequent cMRI and PET demonstrated resolution of the mass and hypermetabolic activity. Discussion: CS is a severe condition that most commonly presents with symptoms of heart failure, conduction abnormalities, and cardiac morphological changes of hypertrophy or thinning. However, it is often missed as a diagnosis, even in patients with extracardiac sarcoidosis. It is rare for CS to present as an isolated cardiac mass, especially in a younger patient as in this case. Advances in imaging techniques such as echocardiography, MRI, and PET have improved the ability to diagnosis CS and provide timely specialized treatment. This case highlights the need to include CS as an important diagnosis on the differential for a patient presenting with conduction abnormalities, heart block, and dyspnea. It also accentuates the critical role of multimodality imaging in working up this disease.

Abstract 4136566: Primary Pericardial Mesothelioma: Diagnostic dilemma and rapid decline

Description of case: A 33-year-old man with no medical history or environment exposures, presented with dyspnea, nausea, and vomiting. He was tachycardic, with jugular venous distension, pulsus paradoxus, low voltage QRS and echocardiogram (TTE) showed a large pericardial effusion with ventricular interdependence. He underwent pericardiocentesis with negative fluid studies, including cytology. Two months later he represented with dyspnea and pleuritic chest pain, was diagnosed with pericarditis, and found to have recurrent pericardial effusion without tamponade. He was treated with aspirin and colchicine and discharged, with surveillance TTE showing a stable pericardial effusion but with significant adhesions and constrictive physiology (confirmed on right heart catheterization). Negative QuantiFERON was obtained and Anakinra started. Two months later he remained symptomatic with new pleural effusions and was sent for positron emission tomography scan which revealed diffuse intensely hypermetabolic pericardial thickening/fluid, up to 3.8 cm in maximal thickness and increased uptake in mediastinal nodes. Next, a cardiac MRI showed extensive circumferential thickening of the pericardial space approximately 2.5 cm in thickness. Both the visceral and parietal pericardium exhibited extensive scattered delayed hyperenhancement. Subsequent pericardial biopsy showed markedly fibrotic pericardium and pathology showed biphasic malignant pericardial mesothelioma. Immunosuppressive medications were stopped, and he underwent thoracentesis. After multidisciplinary discussions, he was started on nivolumab every two weeks and ipilimumab with a plan for surgery based on response to therapy. However, progressive symptoms and worsening constriction physiology led to palliative consultation and comfort care transition, with him dying shortly after. Discussion: Recurrent pericarditis and pericardial effusion, along with negative typical pericardial fluid studies, raised suspicion for a non-benign etiology. Multimodality imaging was employed and led to a pericardial biopsy. Constrictive pericarditis is an uncommon presentation of primary pericardial mesothelioma. Biphasic mesotheliomas from pleural or peritoneal origins are normally treated with systemic therapy with preference for combined immunotherapy. Primary pericardial mesothelioma is associated with a late presentation and high mortality rate, with surgery, if able to be done early appearing to be the recommended approach.

A systematic review and meta-analysis of factors contributing to post-kidney transplant anemia and the effect of erythropoietin-stimulating agents.

The effects of various risk and associated factors on post-kidney transplant anemia (PTA) have not been fully compared and estimated. This meta-analysis aims to elucidate factors contributing to PTA and determine the influence of erythropoietin-stimulating agents (ESAs) on renal outcomes, thus offering potential pathways for enhanced management strategies post-transplant. A systematic review was conducted in electronical database. Studies reporting on risk factors (with cause-effect relationships) and associated factors (without definite cause-effect relationships) of PTA, and the effects of ESAs on post-kidney transplant outcomes, were included. Pooled odds ratios (ORs) and weighted mean differences (WMDs) were analyzed using random-effects models. This systematic review encompassed 38,233 patients from 85 studies. Factors increased PTA risk included African American, older donor age, human antigen leukocyte mismatches, and low pre-transplant hemoglobin levels. Poor allograft function, high interleukine-6, Cytomegalovirus, delayed graft function, allograft rejections, immunosuppressive medications, and renin-angiotensin system blockades were associated with PTA. Native autosomal dominant polycystic kidney disease was a protective factor against PTA. Administration of ESAs with the aim of normalizing hemoglobin levels in patients with chronic allograft dysfunction slowed the decline in eGFR and reduce the risk of death, with a pooled OR of 0.36 (95% CI: 0.14 to 0.89; p = 0.040). The risks and associated factors for PTA have been elucidated, underscoring the need for individualized treatment approaches. Late ESA therapy, aimed at hemoglobin normalization, suggests a renal-protective effect and reduced mortality, which should be considered in the management of PTA. PROSPERO CRD42024545330.

Long-term treatment outcomes of complicated acute diverticulitis in immunocompromised patients

PurposeThe main aim of this study was to determine the short- and long-term outcomes of the non-operative management of acute left-sided complicated diverticulitis (ALCD) in severely immunocompromised patients (IMS group) and compare them with immunocompetent patients (IC group). The secondary aim was to assess the necessity of an elective surgery following a successful prior non-operative management in the IMS group after a non-operative management of the first episode of ALCD.MethodsPatients presented with their first episode of ALCD between 2012 and 2018 were retrospectively reviewed. Only severely immunosuppressed patients were considered for the analysis, including the following: long-term oral or intravenous steroid intake, current malignancy undergoing chemotherapy, chronic kidney disease on hemodialysis, or solid organ transplant with immunosuppressive medication. For each group, demographic data, severity of the episode, management decisions (conservative or operative), and short- and long-term outcomes were recorded and compared. A sub-analysis of patients with ALCD associating and abscess (modified Hinchey classification Ib/II) was performed.ResultsA total of 290 patients were included in the study: 50 among the IMS and 240 among the IC group. The rate of emergent surgery was higher in the IMS group (50.0% vs. 22.5%, p < 0.001) and was associated with increased morbidity (72.4% vs. 50.0%, p = 0.041) and mortality (24.1% vs. 4.3%, p = 0.003). The duration of the hospital stay was significantly longer in the IMS group (15 vs. 8 days, p < 0.001). The final stoma rate was significantly higher in the IMS group (82.1% vs. 22.9, p < 0.001), with a median follow-up of 51.4 months. A total of 141 patients presented ALCD with an abscess; 25 in the IMS and 116 in the IC group. There was a higher rate of surgical intervention among the IMS group as the initial treatment approach (24.0% vs. 5.2%, p = 0.002), even though the conservative treatment had a similar rate of success (81.3% vs. 92.0%, p = 0.178). The recurrence rate following a non-operative approach was similar (IMS: 31.2% vs. 35.4% in the IC group, p = 0.169). Furthermore, 81.2% of non-operatively managed IMS patients (13 out of 16) did not require a surgical intervention at the end of the follow-up, with similar findings in the IC group (78/96, 81.2%, p = 0.148).ConclusionMedical treatment of immunosuppressed patients during their first ALCD episode associated with an abscess is feasible, with a high success rate and results comparable with the IC group. Moreover, taking into account the readmission rates, the need for emergent surgery of the recurrence, and the perioperative mortality and morbidity in the IMS group, conservative management with no differed scheduled surgery seems to be a safe option in this subgroup of patients.

Clinical and Demographic Profile of Patients with Crohn's Disease in Specialized Hospital for Gastrointestinal and Liver Diseases and Surgery in Al-Najaf Province

Background: Crohn’s disease (CD) It is a chronic inflammation that occurs in the digestive system. This disease is widespread in developing countries. Aim of study: To estimation the ratio of clinical and demographic data of CD patients at Specialized Hospital for Gastrointestinal and Liver Diseases and Surgery in AL- Najaf Province. Patients and Methods : Demographic and clinical data were obtained by medical analysis data to patients attended into Specialized Hospital for Gastrointestinal and Liver Diseases and Surgery in AL- Najaf Province from October 2022 to March 2024. Results: Sixty-four patients diagnosed with Crohn's disease participated in this study. The findings indicated that the majority of individuals infected with this disease were women, with the age group of 30 to 39 years being the most prevalent among the infected population. The findings indicate that freelancers and housewives are the most impacted by this disease. The results indicated that the majority of patients visiting the hospital are from Najaf Governorate. The disease was diagnosed through biopsy samples collected from different regions of the digestive system, and the treatment for the majority of patients involved immunosuppressant medications. Conclusions: Despite the increasing incidence, we highlight the Education and a extra intestinal manifestation in this study, and reflecting a high need for hospitalization and immune-modulatory, and uses biological treatment, , and surgery.

The effect of BCG revaccination on the response to unrelated vaccines in urban Ugandan adolescents (POPVAC C): an open-label, randomised controlled trial

Immune responses induced by several important vaccines differ between populations, with reduced responses in low-income and rural settings compared with high-income and urban settings. BCG immunisation boosts immune responses to some unrelated vaccines in high-income populations. We aimed to test the hypothesis that BCG revaccination can enhance responses to unrelated vaccines in Ugandan schoolchildren. We conducted an open-label, randomised controlled trial to compare the effects of BCG revaccination versus no BCG revaccination on the immunogenicity of subsequent unrelated vaccines among adolescents aged 13-17 years who are participants in an urban Ugandan birth cohort study, in which BCG vaccination was documented at birth. Participants were excluded if they had received any of the trial vaccines or related agents when aged 5 years or older. Computer-generated 1:1 randomisation was implemented in REDCap. Participants were excluded if they were concurrently enrolled in other trials; had a clinically significant history of immunodeficiency, or serious psychiatric conditions or moderate to severe acute illnesses; were taking immunosuppressive medications; had allergies to vaccine components, a predisposition towards developing keloid scarring; positive HIV tests or pregnancy tests; were female participants who were lactating; or if they planned to use investigational drugs, vaccines, blood products, or any combination thereof. Trial participants assigned to the BCG revaccination group received the live parenteral BCG-Russia vaccine (Serum Institute of India, Pune, India; 0·1 mL intradermally, right upper arm) at week 0. All participants received yellow fever vaccine (YF-17D; Sanofi Pasteur, Lyon, France; 0·5 mL intramuscularly, left upper arm), live oral typhoid vaccine (Ty21a; PaxVax, London, UK; one capsule per day taken for three alternate days), and quadrivalent virus-like particle human papillomavirus (HPV) vaccine (Merck, Rahway, NJ, USA; 0·5 mL intramuscularly, left upper arm) at week 4; and toxoid vaccines (tetanus-diphtheria; Serum Institute of India; 0·5 mL intramuscularly, left upper arm) and an HPV booster at week 28. An additional HPV vaccination at week 8 was provided to female participants older than 14 years who had not previously been vaccinated. The primary outcomes were yellow fever neutralising antibody titres at 4 weeks post-YF-17D vaccination, Salmonella enterica serovar Typhi (henceforth S Typhi) O-lipopolysaccharide (O:LPS)-specific IgG concentration at 4 weeks post-Ty21a vaccination, and HPV-16 and HPV-18 L1 protein-specific IgG concentration at 4 weeks post-HPV vaccination. Primary outcome assays were conducted at week 8, and at week 52 for tetanus-diphtheria. We conducted an intention-to-treat analysis comparing log-transformed outcomes between trial groups, with results back-transformed to geometric mean ratios (GMRs). The safety population comprised all randomly allocated participants. The trial was registered at the ISRCTN Registry (ISRCTN10482904) and is complete. Between Aug 31 and Oct 12, 2020, we screened 376 potential participants for eligibility. We enrolled and randomly allocated 300 participants to the two groups (151 [50%] to the BCG group and 149 [50%] to the no BCG group). 178 (59%) of 300 participants were male and 122 (41%) were female. 142 (91%) of 151 participants in the BCG group and 139 (93%) of 149 in the no BCG group completed follow-up. There was no effect of BCG revaccination, compared with no BCG revaccination, on the response observed for any vaccine. Yellow fever plaque reduction neutralising reference tests (PRNT50) titres (the reciprocal of the last plasma dilution that reduced by 50%) had a GMR of 0·95 (95% CI 0·75-1·19; p=0·62) and PRNT90 (reciprocal of the last plasma dilution that reduced by 90%) had a GMR of 0·94 (0·74-1·19; p=0·60); IgG to S Typhi O:LPS was 0·99 (0·80-1·23; p=0·94); IgG to HPV-16 was 0·97 (0·69-1·35; p=0·85) and to HPV-18 was 1·03 (0·76-1·40; p=0·83); and toxoid-specific IgG for tetanus was 1·13 (0·87-1·47; p=0·36) and was 1·00 (0·87-1·16; p=0·97) for diphtheria. There were no serious adverse events in either group. We found no evidence that BCG revaccination is an effective strategy to improve immunogenicity of other vaccines in this low-income, urban setting. UK Medical Research Council. For the Luganda translation of the abstract see Supplementary Materials section.

Sarcoidosis Treatment Patterns in the United States: 2016-2022

There are limited FDA-approved medications and real-world data on sarcoidosis treatment in the U.S. and concordance of practice patterns with guideline recommendations have not been well characterized. What are the practice patterns and factors associated with treatment for patients with sarcoidosis in the year following diagnosis? We conducted a retrospective analysis of patients with sarcoidosis from 2016 - 2022 using a multicenter, all-payer, claims database (TriNetX). We ascertained treatments with corticosteroids and/or non-steroidal immunosuppressive medications (methotrexate, mycophenolate, leflunomide, hydroxychloroquine, cyclophosphamide, infliximab, adalimumab, azathioprine, rituximab, and janus kinase inhibitors) within one year of diagnosis. We summarized treatment rates, sequence of prescribed medications by mean rank, and used multivariable logistic regression analyses to identify factors associated with treatment. Out of 13,330 patients with sarcoidosis meeting inclusion, 5,671 (42.5%) received treatment within a year of diagnosis. Of those treated, 60% received steroids alone, 13% received non-steroidal immunosuppressives alone, and 27% received both. Further, 25% of treated patients received a non-steroidal immunosuppressive as their first medication. Corticosteroids had the lowest mean rank order, indicating they were, on average, the first medication initiated. Among those with pulmonary or cutaneous involvement, the second medication initiated on average was hydroxychloroquine, while in those with cardiac or neurologic involvement it was adalimumab and mycophenolate, respectively. Factors associated with higher odds of treatment were Black race, organ involvement at baseline (pulmonary, cardiac, and neurologic), and comorbid diagnoses (fatigue, hypercalcemia, and ILD). Within the first year of diagnosis, 43% of patients with sarcoidosis were started on treatment. Non-steroidal immunosuppressives were used in 40% of treated patients. While factors associated with treatment initiation aligned with guideline recommendations, practice patterns of treatment were variable, particularly in choice and sequence of non-steroidal immunosuppressive therapy, underscoring the need for future trials and comparative effectiveness studies.

OA08 Ocrelizumab in pregnancy in a patient with juvenile onset systemic lupus erythematosus

Abstract Introduction Juvenile-onset systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease that results in increased disease activity compared to adult-onset SLE. jSLE in pregnancy results in a greater incidence of disease flares as well as adverse pregnancy outcomes. Management of SLE in pregnancy is particularly difficult due to lack of safety data for immunosuppressant medications and is therefore limited. Ocrelizumab is a humanised monoclonal antibody that selectively targets CD20 B cells and is approved for the treatment of multiple sclerosis. Despite never being trialled in a patient with active SLE in pregnancy, this case demonstrates its use with a successful outcome. Case description An 18-year-old female was diagnosed at age 14 with juvenile onset systemic lupus erythematosus with the presence of a photosensitive malar rash, arthralgia, alopecia, aphthous ulcers and headache. At the time of diagnosis her investigations revealed ANA 1:5120 with homogenous pattern, high dsDNA, low C3 and C4, thrombocytopenia, antibodies to Smith, Ro, RNP, anti-Rib-P, strongly positive lupus anticoagulant antibodies and low titre anti-cardiolipin IgG and IgM. Previous treatment included methotrexate, mycophenolate mofetil and cyclosporin which were discontinued either due to patient choice, inefficacy or adverse reaction. Azathioprine was contraindicated due to low TMPT. Rituximab was trialled and although effective had to be stopped due to adverse reaction. Unfortunately, she experienced a primigravida pregnancy loss at 15-20 weeks secondary to active SLE and pre-eclampsia. Shortly after this, she developed a rare case of anti-fascin antibody neuropathy and was treated with ocrelizumab. Six months later during her second pregnancy, she was treated with hydroxychloroquine 400 mg, aspirin 150 mg, folic acid 5 mg and low molecular weight heparin prophylaxis which were continued throughout the pregnancy. Due to concerns of active lupus at 13 weeks due to facial rash and fatigue, prednisolone was commenced at 10 mg daily and continued. After careful consideration, Ocrelizumab was given in the second trimester at 17 and 19 weeks’ gestation. Following this, symptoms remained under control and disease activity was low with normal C3/C4 and dsDNA levels without significant proteinuria. A newborn baby was delivered at 38 weeks by caesarean section without complication or foetal abnormalities. Both the mother and baby remain under close follow- up but have not demonstrated adverse outcomes at 3 months postpartum. Discussion This case demonstrates the use of Ocrelizumab in the second trimester of a high-risk pregnancy complicated by active jSLE. At present, there is no license for use of Ocrelizumab in SLE and no safety data on its use in pregnancy. However, there was a good outcome for this patient which resulted in no antenatal or postpartum complications and the successful birth of a healthy newborn without foetal abnormalities. Ocrelizumab is used for the treatment of early relapsing-remitting multiple sclerosis (RRMS) and is increasingly used by neurologists in women of childbearing age despite being unlicensed for use in pregnancy. Concerns of its use in pregnancy surround B cell depletion in the neonate which while tends to be transient, causes significant concern regarding long term immunological development and response to vaccination. B cell depleting therapies are widely used in the context of active and refractory SLE and therefore use of Ocrelizumab has been evaluated in cases of SLE in two phase III clinical trials. The first study examined the efficacy of Ocrelizumab in SLE without renal involvement (BEGIN) and the second recruited patients with lupus nephritis (BELONG). The BEGIN study was terminated early due to lack of response and the BELONG study was terminated due to a significant increase in serious infections (in the Ocrelizumab plus mycophenolate treatment group). However, results on disease activity were positive with complete renal response being achieved non-statistically more frequently in the Ocrelizumab treated patients versus placebo. Real world evidence shows the importance of achieving disease control in SLE around pregnancy to prevent adverse outcomes. The decision for the use of Ocrelizumab therefore needs to be balanced carefully against potential harm to the baby either from direct foetal exposure to the drug, or from gestation in an immunocompromised mother. Key learning points • Pre-pregnancy counselling is of paramount importance in severe cases of active SLE and when possible, pregnancy should be postponed in these instances until disease activity is stabilised with contraception counselling offered to those on teratogenic immunosuppressive agents. • A multidisciplinary approach to the management of complex SLE in pregnancy in essential with obstetrician, midwife, maternal medicine physician and rheumatologist input. • The benefit of potentially life-saving immunosuppressive treatment should be carefully balanced against the poor outcomes of active SLE in pregnancy and decisions should be made on a case-by-case basis.

Erysipelothrix rhusiopathiae-associated bloodstream infection in a patient with systemic lupus erythematosus: a case report and literature review

Introduction. Systemic human infections caused by Erysipelothrix rhusiopathiae have been increasingly reported especially within immunocompromised hosts and those with significant occupational exposure to livestock and aquatic animals. We report a case of E. rhusiopathiae bacteraemia in a patient with systemic lupus erythematosus (SLE) and present a literature review on clinical outcomes and microbiologic diagnosis for this organism. Case presentation. A 43-year-old female patient was reporting a 1-month history of intermittent fevers. She recently increased her immunosuppression medication for her underlying SLE on the advice of her rheumatologist. The patient sustained a finger laceration from butchering cattle meat 2 weeks after the onset of her initial symptoms, with worsening index finger swelling and increased febrile episodes. Two weeks post-injury, multiple blood cultures were drawn, and each isolated Gram-positive bacilli. Given her recurrent intermittent fevers, there was a concern for ongoing infection, and therefore, intravenous vancomycin was started with prompt referral to an outpatient parenteral antibiotic therapy clinic. The Gram-positive bacillus was confirmed as E. rhusiopathiae via matrix-assisted laser desorption/ionization-time of flight analysis. Given intrinsic resistance to vancomycin, vancomycin was switched to intravenous ceftriaxone as targeted antimicrobial therapy for 2 weeks. Reassuringly, there was no echocardiographic evidence of infective endocarditis, warranting the prolonged treatment course. Post-treatment, she remained symptom-free with the resolution of joint symptoms and fevers. Conclusion. Our report illustrates a case of E. rhusiopathiae bacteraemia from an immunodeficient host, with prompt microbiologic diagnosis and intervention with appropriate antimicrobial coverage. Literature reflects the rarity of this infection, predilections to specific susceptible hosts and the importance of raising awareness of zoonotic infections.

Evaluating the risk of cardiovascular events associated with different immunosuppression treatments for glomerular diseases.

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials.

Clinical findings, prognostic factors, and outcome of protein-losing nephropathy in cats: A retrospective study.

Primary glomerular disease resulting in protein-losing nephropathy (PLN) is an uncommon cause of chronic kidney disease in cats, yet is important to recognize because it warrants specific treatment that impacts outcome. Characterize clinicopathologic findings, prognostic indicators, and short- (≤30 days) and long-term survival of cats with PLN. Thirty-seven cats with naturally occurring PLN. Medical records of cats with PLN admitted to a veterinary teaching hospital were retrospectively reviewed. Median age was 3 years (range, 1.5-11.5 years) and 17/37 (46%) were males. Short-term survival was 57%. The estimated median survival time of all cats was 424 days (95% confidence interval [CI], 0-1098 days). Common clinical signs included lethargy (57%), edema (46%) and weight loss (35%). Edema was more common in short-term survivors compared with nonsurvivors (odds ratio [OR], 0.21; 95% CI, 0.05-0.86-20.4; P = .04). Serum creatinine concentration at presentation was negatively associated with long-term survival (OR, 1.3; 95% CI, 1.03-1.52; P = .01). Administration of immunosuppressive and antiproteinuric medications was more common among short-term survivors compared with nonsurvivors (18/20 [90%] vs 9/16 [56%]; OR, 7.0; 95% CI, 1.2-40.8; P = .05 and 17/20 [85%] vs 7/16 [44%]; OR, 7.3; 95% CI, 1.5-35.2; P = .01, respectively). Partial or complete remission was documented in 11/31 (36%) cats and was associated with both short (OR, 3.3; 95% CI, 1.7-6.5; P < .001) and long-term survival (P = .003). Cats with PLN have a guarded prognosis, but achieving remission improves outcome. Cats presented with edema rather than azotemia are more likely to respond to treatment.

The Impact of Reduced Immunosuppression on Alloimmunity: A Retrospective Study of Pediatric Kidney Transplant Recipients.

Kidney transplantation is the best treatment for end-stage kidney disease but requires immunosuppressive medications, which have significant side effects. Many pediatric recipients experience these side effects, leading to dosage reductions, which potentially increase the risk of alloimmunity. We aimed to describe the alteration in immunosuppressive medication, explore the reasons for the reductions, and assess the potential impact on alloimmunity. Data from 49 pediatric kidney transplant recipients receiving an allograft from 2009 to 2020 were retrospectively studied. The recipients were screened for HLA antibodies after the transplantation. The median age of recipients was 11 years (IQR 8), with a median follow-up of 5 years (IQR 5). Eighty percent of the transplantations were corticosteroid-free. During follow-up, 11% developed de novo donor-specific antibodies (dnDSA), and 60% had detectable HLA antibodies. The 1-year rejection rate was 4%. Immunosuppressive medication was altered substantially in most recipients, resulting in 72% being on mono- or dual therapy with a reduced mycophenolate mofetil (MMF) dosage by the end of the first posttransplant year. The median MMF dose was nearly half of the intended. Tacrolimus levels were maintained close to the target of 5 ng/mL. No association was found between reduced immunosuppression and dnDSA or rejections. Reductions were primarily due to MMF-related side effects: leukopenia in 77%, gastrointestinal issues in 34%, and infections with Epstein-Barr virus, cytomegalovirus, and BK polyomavirus in 49%. Reduced MMF with a sufficient trough tacrolimus level in a population of mainly corticosteroid-free pediatric kidney transplant recipients did not lead to unacceptable alloimmunity.

Cryptosporidium spp. Infection in Adult Kidney Transplant Patients: A Systematic Review and Meta-Analysis.

Background: Diarrhea frequently occurs after vascular organ transplantation, including kidney transplants. This may result from non-infectious factors, adverse effects of immunosuppressive medications, or infections caused by various pathogens, including viruses, bacteria, fungi, or parasites, for example, intestinal protozoan parasites such as Cryptosporidium spp., which are particularly dangerous for immunocompromised patients. Methods: This review is based on scientific articles sourced from validated databases such as PubMed, the National Center for Biotechnology Information (NCBI), ScienceDirect, and Google Scholar. The primary search was conducted on 12-13 July 2024, using the keywords 'Cryptosporidium' AND 'cryptosporidiosis' AND 'kidney' AND 'transplant' AND 'adult'. Inclusion criteria encompassed human studies, case reports, peer-reviewed journal publications, review articles, and research articles in English. Exclusion criteria included studies not in English, gray literature (e.g., conference proceedings and abstracts), and data related to pediatric patients (under 18 years old) and HIV patients. Results: This systematic review and meta-analysis have highlighted an often-overlooked connection between Cryptosporidium spp. infections in adult kidney transplant recipients (KTR). Furthermore, it includes an analysis of the clinical presentation, diagnosis, and treatment of Cryptosporidium spp. infection in these patients, based on available case reports. Our study demonstrates that adult kidney transplant patients are at a significantly higher risk of acquiring Cryptosporidium spp. compared to healthy participants. Conclusions:Cryptosporidium spp. infections can be asymptomatic, making it essential to screen both symptomatic and asymptomatic kidney transplant recipients. The clinical presentation of cryptosporidiosis typically involves digestive symptoms and can be complicated by biliary tract involvement. In KTR patients presenting with diarrhea, it is crucial to not only test for Cryptosporidium spp. but also to rule out bacterial and viral etiologies, including infections such as C. difficile, C. colitis, Clostridium spp., and rotavirus. The diagnosis of Cryptosporidium spp. infections primarily relies on microscopic methods, which are known for their low sensitivity. Therefore, diagnostic approaches should include both direct methods and, where possible, molecular techniques. Based on the analyzed cases, the most effective treatment results were achieved with reduction in immunosuppression if possible (strong, very low) and nitazoxanide at a dose of 500 mg twice daily for 14 days. Considering the public health implications of our findings, the current epidemiological data underscore the need for further research to develop effective prevention and intervention strategies against cryptosporidiosis. Preventive measures, regular screening programs, and the treatment of Cryptosporidium spp. infections should be integrated into the clinical care of transplant patients. It is also important that patients are informed about environmental risk factors.

Post-transplant glomerular diseases: update on pathophysiology, risk factors, and management strategies

Abstract In recent years, advancements in immunosuppressive medications and post-transplant management have led to a significant decrease in acute rejection rates in renal allografts and consequent improvement in short-term graft survival. In contrast, recent data have shown an increased incidence of post-transplant glomerular diseases, which currently represent a leading cause of allograft loss. Although pathogenesis is not fully understood, growing evidence supports the role of inherited and immunological factors and has identified potential pre- and post-transplant predictors. In this review, we illustrate recent advancements in the pathogenesis of post-transplant glomerular disease and the role of risk factors and immunological triggers. In addition, we discuss potential prevention and management strategies.

IgG4-Related Disease Involving the Ear: A Case Report.

IgG4-related disease is a chronic inflammatory disease with widespread clinical presentation. It mimics various malignant, infectious, and inflammatory conditions, leading to confusion in diagnosis and management. Otological manifestations, though relatively rare, can lead to significant complications. A 45-year-old male with a recent history of ventilation tube placement in the right ear presented with a sensation of imbalance associated with profound hearing loss. He was managed in line of acute otitis media with labyrinthitis with steroids and antibiotics and removal of the ventilation tube. He returned in one week and presented with right-sided lower motor neuron-type facial paresis. Computed tomography images of the temporal bone showed a soft tissue density lesion in the right middle ear cavity extending to the mastoid antrum. He underwent a right cortical mastoidectomy with decompression of the facial nerve. Histopathology and immunohistochemistry of granulation tissues from the middle ear and the mastoid revealed evidence suggestive of probable IgG4 disease. IgG4-related disease is a relatively new entity, and its pathogenesis has not been properly understood. IgG4 subclass has been involved in this disease resulting in fibro-inflammatory conditions leading to tumor-like masses or fibrosis of the affected organs. Treatment includes glucocorticoids and immunosuppressant medications.

Impact of Immunosuppressants and Vaccination on COVID-19 Outcomes in Autoimmune Patients and Solid Organ Transplant Recipients: A Nationwide Propensity Score-Matched Study.

This study investigates the impact of varying degrees of immunosuppression on the clinical outcomes of immunocompromised individuals, particularly those with autoimmune diseases or post-solid organ transplant statuses, in the context of COVID-19. By focusing on these highly vulnerable populations, the study underscores the significant health inequalities faced by immunocompromised patients, who experience disproportionately worse outcomes in comparison to the general population. A retrospective cohort analysis of the K-COV-N dataset was conducted, comparing the effects of immunosuppression in autoimmune and transplant groups with matched control groups. Propensity score matching was employed to minimize inequalities in baseline characteristics, ensuring a more equitable comparison between immunocompromised and non-immunocompromised individuals. Outcomes included COVID-19-related in-hospital mortality, 28-day mortality, ICU admissions, and the need for respiratory support among 323,890 adults in the Republic of Korea. Patients with cancer or other immunosuppressive conditions, such as HIV, were excluded. Subgroup analyses assessed the influence of specific immunosuppressive medications and vaccination extent. Significantly elevated in-hospital mortality was found for patients with autoimmune diseases (adjusted Odds Ratio [aOR] 2.749) and transplant recipients (aOR 7.567), with similar patterns in other outcomes. High-dose steroid use and a greater number of immunosuppressant medications markedly increased the risk of poor outcomes. Vaccination emerged as a protective factor, with a single dose substantially improving outcomes for autoimmune patients and at least two doses necessary for transplant recipients. Immunocompromised patients, particularly those with autoimmune diseases and transplant recipients, are highly vulnerable to severe COVID-19 outcomes. High-dose steroid use and multiple immunosuppressants further increase risks. Vaccination significantly improves outcomes, with at least one dose benefiting autoimmune patients and two doses necessary for transplant recipients. Personalized vaccination schedules based on immunosuppression levels are essential to mitigate healthcare inequalities and improve outcomes, particularly in underserved populations, informing both clinical and public health strategies.

Validation, implementation and quality control of a Torque Teno Virus qPCR in a multinational clinical trial

BackgroundImmunosuppressive medication after organ transplantation is usually dosed through therapeutic drug monitoring. Trough levels of antirejection medication however, do not adequately predict rejection or infections. The TTVguideIT trial is a multinational clinical trial evaluating the safety of Torque Teno Virus (TTV) load assessed by qPCR, as an alternative to trough level tacrolimus dosing. MethodsPrior to, and during the clinical trial, the inter-and intra-laboratory variability, accuracy, and precision of the TTV R-GENE® assay was evaluated through analysis of internal quality control (IQC), external quality assessment (EQA) and linearity panels performed by the thirteen participating clinical virology laboratories, each using their standard testing platforms. ResultsIQC samples with a target of 4 log10 copies/mL (cp/mL) were tested by the participating laboratories 130 times during the implementation phase and 987 times during the trial phase. They showed excellent accuracy, with an inter-laboratory standard deviation (SD) of 0.17 log10 cp/mL, and an intra-laboratory SD of 0.03 to 0.20 log10 cp/mL during the implementation phase, and an inter-laboratory SD of 0.19 log10 cp/mL, and an intra-laboratory SD 0.07 to 0.18 log10 cp/mL during the trial phase. Three EQA panels and three linearity panels showed similarly small variability during implementation as well as within the trial phase. ConclusionThis data shows that TTV load measurement can be standardized for use in a multinational clinical trial. By using IQC, LP and EQA samples, the quality and integrity of the assay can be compared between laboratories and precise and accurate results can be generated.

Long-Term Outcomes of Rituximab-Treated Adult Patients with Podocytopathies

Background: Long-term outcomes of rituximab-treated adult patients with podocytopathies (either minimal change disease or focal segmental glomerulosclerosis) are largely unknown. Methods: A retrospective study at 30 nephrology departments from 15 countries worldwide included rituximab-treated adults with primary podocytopathies and a minimum clinical follow-up of 36 months. The primary outcome was relapse-free survival at 36 months. Results: 183 adult patients (n=64 with focal segmental glomerulosclerosis and n=119 with minimal change disease) with difficult-to-treat nephrotic syndrome (68% steroid-dependent/frequently relapsing, 22% steroid-resistant, 85% previously treated with two or more lines of immunosuppressive therapy) were treated with rituximab as part of a remission induction regimen. Complete or partial remission at 6 months after rituximab treatment was achieved in 82%. Eighty-three of 151 (55%) initial responders achieved long-term relapse-free survival over three years. Maintenance therapy with rituximab was associated with a better relapse-free survival (HR 2.05, 95% CI: 1.07-3.91), irrespective of the dosing regimen. At 36 months, 61% of initial responders receiving maintenance therapy with rituximab achieved long-term relapse-free survival and withdrawal of all concomitant immunosuppressive medication compared to 36% of patients without maintenance treatment (OR 2.69, 95% CI: 1.27-5.73). Relapses per year were reduced from an annual relapse rate of 1.0 (95% CI: 1.0-1.7) before to 0.17 (95% CI: 0.00-0.24) relapses/year after rituximab initiation. Over the 36 months of follow-up, a stable course of estimated glomerular filtration rate (eGFR) was observed in those who initially responded with either complete or partial remission, whereas non-responders experienced a reduction in eGFR reaching -11 (95% CI: -18 to -8) mL/min/1.73m2 . Conclusions: Rituximab facilitated achievement of initial and long-term response in a majority of adult patients with difficult-to-treat podocytopathies. Maintenance treatment with rituximab further associated with long-term relapse-free survival over three years. Non-response to initial rituximab treatment was associated with poor kidney prognosis.