Perspective on oral medication adherence among patients with acute graft-versus-host disease: a qualitative descriptive study.

PURPOSE: Despite the importance of adherence to immunosuppressants (IMMs) after an allogeneic haematopoietic stem cell transplant (HSCT) for the treatment of acute graft-versus-host disease (aGvHD), no studies to date have reported the experiences of such patients concerning medication adherence (MA). Therefore, the aim of the study was to explore the perspective on MA to immunosuppressive oral therapy among allogeneic HSCT patients with aGvHD. METHODS: A qualitative descriptive study following a reflexive thematic analysis methodological approach was performed involving a purposive sample of 16 patients with aGvHD who were being cared for in the outpatient setting of a bone marrow transplant centre and were willing to participate. Semi-structured audio-recorded interviews were conducted, transcribed verbatim and thematically analysed; member checking was performed. COnsolidated criteria for REporting Qualitative research (COREQ) and the ESPACOMP Medication Adherence Reporting Guideline were followed. RESULTS: Participants aged 25-74 years and mostly males (62.5%) were recruited for this study; 56.2% developed grade I, 37.5% grade II and 6.3% grade III aGvHD; 56.2% were receiving treatment with both cyclosporine and prednisone. Patients' perspectives have been summarised into four themes, named: "Transiting from an external obligation to a habit"; "Being in the middle between the negative and positive effects of the IMMs"; "Failure to systematically respect the rules"; and "Adopting personal strategies to become adherent". After difficulties with the perception of feeling obliged, patients became used to adhering to IMMs. Although there were failures in systematically taking the medication correctly and there were episodes of non-adherence, the adoption of personal strategies helped patients to become adherent to their medication schedules. CONCLUSIONS: MA in patients with aGvHD is a complex behaviour and is often a challenge. These results can help healthcare professionals and centres to understand how best to design tailored strategies and behavioural interventions to maximise patients' MA to IMMs.

Diverse Clinical and Immunological Profiles in Patients with IPEX Syndrome: a Multicenter Analysis from Turkey.

PURPOSE: Immunodysregulation, Polyendocrinopathy, Enteropathy, and X-linked syndrome (IPEX), caused by pathogenic FOXP3 variants, is a rare autoimmune disorder with diverse clinical features, including early-onset diabetes, eczema, and enteropathy. Atypical cases show milder symptoms and unique signs, requiring different treatments. Therefore, there are ambiguities in the accurate diagnosis and management of IPEX. We sought to present clinical, genetic, and immunological assessments of 12 IPEX patients with long-term follow-up to facilitate the diagnosis and management of the disease. METHODS: Clinical findings and treatment options of the patients were collected over time. Lymphocyte subpopulations, protein expressions, regulatory T (Treg) and circulating T follicular helper (cTFH) cells, and T-cell proliferation were analyzed. RESULTS: Predominant presentations included autoimmunity (91.6%), failure to thrive (66.7%), and eczema (58.3%). There were four classical and eight atypical IPEX individuals. Allergic manifestations were more common in atypical patients. Notably, chronic diarrhea demonstrated heightened severity compared to other manifestations. Four patients (33.3%) demonstrated eosinophilia, and nine (75%) showed high serum IgE levels. Most patients exhibited normal percentages of Treg cells with reduced CD25, FOXP3, and CTLA-4 expressions, corrected after hematopoietic stem cell transplantation (HSCT). Compared to healthy controls, the TH2-like skewing accompanied by reduced TH17-like responses was observed in cTFH and Treg cells of patients. Overall, nine patients (75%) received immunosuppressants (ISs), and six (50%) underwent HSCT, which was the only treatment revealing sustained control. Sirolimus was used in six patients and showed better control than other ISs. CONCLUSIONS: The first cohort from Turkey with long-term follow-up results, comparing typical and atypical cases, provides insights into the outcomes of different therapeutic modalities and T- cell subtype changes in IPEX syndrome.

Immunosuppressant therapy averts rejection of allogeneic FKBP1A-disrupted CAR-T cells.

Chimeric antigen receptor (CAR) T cells from allogeneic donors promise "off-the-shelf" availability by overcoming challenges associated with autologous cell manufacturing. However, recipient immunologic rejection of allogeneic CAR-T cells may decrease their in vivo lifespan and limit treatment efficacy. Here, we demonstrate that the immunosuppressants rapamycin and tacrolimus effectively mitigate allorejection of HLA-mismatched CAR-T cells in immunocompetent humanized mice, extending their in vivo persistence to that of syngeneic humanized mouse-derived CAR-T cells. In turn, genetic knockout (KO) of FKBP prolyl isomerase 1A (FKBP1A), which encodes a protein targeted by both drugs, was necessary to confer CD19-specific CAR-T cells (19CAR) robust functional resistance to these immunosuppressants. FKBP1AKO 19CAR-T cells maintained potent in vitro functional profiles and controlled in vivo tumor progression similarly to untreated 19CAR-T cells. Moreover, immunosuppressant treatment averted in vivo allorejection permitting FKBP1AKO 19CAR-T cell-driven B cell aplasia. Thus, we demonstrate that genome engineering enables immunosuppressant treatment to improve the therapeutic potential of universal donor-derived CAR-T cells.

Reproductive Health in Kidney Transplant Recipients.

Increasing number of women with kidney transplants are of reproductive age and desire successful pregnancies. Successful outcomes of pregnancy can be achieved with preconception counseling, education about contraception use, the timing of pregnancy (delaying by first year post-transplant), and the choice of immunosuppression medication. Ensuring stable renal function including optimized creatinine, proteinuria, and blood pressure increases successful outcomes. Pregnancy with kidney transplant has an increased risk of preeclampsia, gestational diabetes militeus, cesarean section, and preterm delivery. Multidisciplinary cooperation with high-risk obstetrics and transplant nephrologists is vital.

Pharmacokinetic-based Dosing Individualization of Mycophenolate Mofetil in Solid Organ Transplanted Patients.

Mycophenolate mofetil (MMF) is an immunosuppressant drug approved for prophylaxis of transplant rejection in patients undergoing solid organ transplantation and is further employed in management of various autoimmune disorders. MMF exhibits notable pharmacokinetic inter- and intraindividual variability necessitating tailored therapeutic approaches to achieve optimal therapeutic outcomes while mitigating risks of adverse effects. The objective of this review was to summarize factors that influence the pharmacokinetics of MMF and its active metabolite mycophenolic acid in order to deduce recommendations for personalized treatment strategies. Presumed predictors were analysed in relation to each of the four pharmacokinetic phases, providing tools and targets for MMF dosing optimization amenable to clinical implementation.

The impact of cadaveric donor transplant on the development of chronic rhinosinusitis and recalcitrant disease.

KEY POINTS: The study found a higher incidence of chronic rhinosinusitis (CRS) and recalcitrant CRS in cadaveric organ transplant recipients compared to those receiving living donor transplants. Recipients of cadaveric transplants were 1.32 times more likely to develop CRS and 1.68 times more likely to develop medically recalcitrant CRS. Living kidney transplants significantly reduced the risk of developing CRS (OR = 0.12) and recalcitrant CRS (OR = 0.11), highlighting a potentially protective effect against these conditions. In contrast, cadaveric liver transplants were associated with an increased risk of CRS and medically recalcitrant CRS. Kaplan-Meier survival analysis indicated a significant difference in time to CRS onset between cadaveric and living donor transplants. Median time to CRS onset was longer for living donor recipients (21.1 months) compared to cadaveric recipients (15.6 months). This study underscores the need for transplant teams and otolaryngologist to consider donor type during transplant follow-up due to differing risks of CRS development.

Rheumatoid arthritis complicated with cervical actinomycosis and ureteral obstruction: A case report and literature review. / ç±»é£Žæ¹¿å ³èŠ‚ç‚Žåˆå¹¶å®«é¢ˆæ”¾çº¿èŒç— åŠè¾“å°¿ç®¡æ¢—é˜»1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts, often misdiagnosed due to its similarity to many infectious and non-infectious diseases. This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics, including methotrexate, leflunomide, and infliximab, leading to recurrent joint pain, poorly controlled rheumatoid arthritis activity, and persistent elevation of white blood cell counts. Abdominal CT revealed a pelvic mass and right ureteral dilation. Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules, indicating actinomycosis. The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide, hydroxychloroquine sulfate, and tofacitinib, resulting in improved joint symptoms and normalized white blood cell counts. After 2 years of follow-up, the patient remained stable with no recurrence. This case highlights the importance of clinicians being vigilant for infections, particularly chronic, occult infections from rare pathogens, in rheumatoid arthritis patients on potent immunosuppressants and biologics, advocating for early screening and diagnosis.

Methotrexate and Rituximab Use in Highly Recurrent Idiopathic Subglottic Stenosis.

OBJECTIVE: To evaluate the impact of methotrexate and rituximab therapy on highly recurrent idiopathic subglottic stenosis (iSGS) patients with a negative antineutrophil cytoplasmic antibody titer cANCA(-). METHODS: This was a retrospective cohort study of highly recurrent iSGS patients who recurred within 1 year or less and were treated with methotrexate (MTX), and rituximab (RTX), or a combination of both at different time points (MTX/RTX). Average surgical durations before and after drug treatment were summarized, and the differences were calculated. RESULTS: A total of 21 female patients with median age of 62 years were included. Fifteen patients were treated with MTX, three were treated with RTX, and five treated with both. Patients treated with immunosuppressants showed a trend toward longer intervals between operations (mean pre-drug interval: 338; mean post-drug interval: 697 days) (p-value = 0.25). Three patients did not recur following drug initiation with median follow-up of 1265 days. All three treatment groups demonstrated a trend toward increased post-drug recurrence intervals (MTX: 444 days, RTX: 374 days, MTX/RTX: 55 days), that was not statistically significant. Patients with prior dilations demonstrated longer post-drug recurrence intervals (mean pre-drug interval: 341 days, mean post-drug interval 978 days) (p-value = 0.17). Four patients in the cohort with the highest recurring disease improved from mean 129 days between operations to 509 days with drug therapy. The most common drug side effect was nausea (16%). CONCLUSION: MTX and RTX may be treatment options for some highly recurrent iSGS patients. Initial results are variable and demonstrate a need for further research on drug candidacy. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Efficacy and safety of pharmacological treatments for autoimmune disease-associated interstitial lung disease: A systematic review and network meta-analysis.

BACKGROUND: Immunosuppressants, biologic agents, antifibrotic drugs, and other drugs can be used to treat autoimmune disease-associated interstitial lung disease (ILD), but the preferred treatment is uncertain. We aimed to evaluate the efficacy and safety of multiple drugs in the treatment of autoimmune disease-associated ILD. METHODS: PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials and ClinicalTrials.gov were searched for relevant randomized controlled trials (RCTs) from inception to July 2023. Primary outcomes were percentage of predicted forced vital capacity (FVC% predicted) and discontinuations for adverse events (AEs). We estimated summary mean differences (MDs) and odds ratios (ORs) using network meta-analysis with fixed effects. RESULTS: The analysis is based on 15 RCTs involving 1832 patients. In terms of FVC% predicted, mycophenolate mofetil (MMF) (MD 1.27, 95 % credible interval [CrI] 0.08 to 2.43), cyclophosphamide (1.89, 0.10 to 3.68), rituximab (9.29, 2.79 to 15.80), tocilizumab (6.30, 3.27 to 9.34), nintedanib (1.71, 0.54 to 2.88), pirfenidone (2.03, 0.65 to 3.40) and nintedanib+MMF (2.43, 0.95 to 3.89) were more effective than placebo. Analysis based on a small sample size showed that riociguat also had good therapeutic potential when compared with placebo. By contrast, bosentan and pomalidomide showed no significant difference compared with placebo. Regarding discontinuations for AEs, nintedanib (OR 2.09, 95 %CrI 1.20 to 3.73) and pirfenidone (3.46, 1.31 to 10.56) were associated with higher dropout rates than placebo, and the combination therapy of nintedanib+MMF did not increase the risk of AEs compared with nintedanib monotherapy. CONCLUSIONS: MMF, cyclophosphamide, rituximab, tocilizumab, nintedanib and pirfenidone are effective in the treatment of autoimmune disease-associated ILD. The efficacy of riociguat and the superiority of combination therapy need to be demonstrated in more RCTs. The tolerance of nintedanib and pirfenidone is a concern, but most of their AEs are mild and controllable.

Paediatric Uveitis - the uniqueness in clinical presentation and the efficacy of biologics treatment.

AIMS: To evaluate unique clinical characteristics of paediatric uveitis in our locality and treatment outcomes especially the efficacy of biologics. METHODS: This was a retrospective cohort. RESULTS: 37 paediatric uveitis cases involving 67 eyes were included. Male-to-female ratio was 1:1.3. Mean age of uveitis onset was 11 ± 3.7 (4-18). 81.1% cases suffered from bilateral uveitis. 75.7% cases were chronic uveitis. Nearly half of the cases (40.5%) presented with anterior uveitis. The predominant diagnosis of uveitis in our cohort was idiopathic. Unlike studies from other populations, the associated systemic conditions in this mostly Chinese cohort were Behçet's disease (8.1%), tubulointerstitial nephritis and uveitis (8.1%) and HLA-B27 associated uveitis (8.1%). Steroid response was a common phenomenon, observed in 40.5% of cases. The most common complication was posterior synechiae (45.9%), followed by cataract (37.8%), glaucoma (27.0%), band keratopathy (18.9%) and macular oedema (13.5%). 3/37 patients encountered either first attack of uveitis or flare after receiving COVID-19 vaccine. 54.1% of patients required systemic steroid for disease control. The majority required steroid sparing immunotherapy, including Methotrexate (43.2%), Mycophenolate Mofetil (24.3%), Cyclosporine A (8.1%), Azathioprine (5.4%) and Tacrolimus (2.7%). Resistant cases required biologics including tumour necrosis factor alpha inhibitors (Adalimumab 32.4%, Infliximab 2.7%) and interleukin-6 inhibitors (Tocilizumab 2.7%). CONCLUSIONS: Clinical presentation of the local paediatric uveitis differs from previously described features in Caucasian and other populations. According to our experience as a tertiary eye centre, Behçet's disease, tubulointerstitial nephritis and uveitis and HLA-B27 associated uveitis were more often encountered than Juvenile Idiopathic Arthritis associated uveitis. Our report evaluated the efficacy of immunomodulatory therapy and biologics in controlling uveitis and reducing ocular complications.

[Anti-Neutrophil Cytoplasmic Antigens (ANCA)-associated vasculitis: Current therapeutics]. / Vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) : actualités thérapeutiques.

ANCA-associated vasculitis brings together three diseases, granulomatosis with polyangiitis, microscopic polyangiitis and eosinophilic granulomatosis with polyangiitis. This group of diseases has benefited over the last 3 decades from major therapeutic advances both in terms of therapeutic strategies and availability of new drugs, mainly for targeted therapies. Treatments, whether conventional or not, include an induction phase followed by a maintenance phase. Induction treatment today poses few problems. It is essentially based on the combination of corticosteroids and rituximab or cyclophosphamide. Remission is achieved in less than 6 months and maintenance treatment, preventing relapses, is then started. We showed that the best maintenance treatment was rituximab, surpassing the efficacy of methotrexate or azathioprine. During this phase, corticosteroid therapy is stopped or given at a very small dose. In Eosinophilic Granulomatosis with Polyangiitis (GEPA), the strategy is slightly different and there is a lack of prospective trials to demonstrate the benefits of rituximab or mepolizumab (anti-IL5) in inducing remission. Regarding maintenance treatment, prolonged corticosteroid therapy (orally and/or inhaled) is often necessary to control asthmatic disease. Only mepolizumab has shown its ability to prevent relapses and reduce the dose of corticosteroids controlling asthma. The current questions posed by maintenance treatment are its duration which could be variable and adapted to the risk of relapse and the risks induced by prolonged immunosuppression, particularly infectious.

Title: Vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) : actualités thérapeutiques. Abstract: Les vascularites associées aux anticorps anti-cytoplasme des polynucléaires neutrophiles (ANCA) réunissent trois maladies, la granulomatose avec polyangéite, la polyangéite microscopique et la granulomatose éosinophilique avec polyangéite. Ce groupe de maladies a bénéficié au cours des trois dernières décennies d'avancées thérapeutiques majeures tant en termes de stratégies thérapeutiques que de mise à disposition de nouveaux médicaments, essentiellement pour des thérapies ciblées. Les traitements, conventionnels ou non, comprennent une phase d'induction suivie d'une phase d'entretien. Le traitement d'induction pose aujourd'hui peu de problèmes. Il est essentiellement fondé sur l'association corticoïdes et rituximab ou cyclophosphamide. La rémission est obtenue en moins de 6 mois et un traitement d'entretien, préventif des rechutes, est alors initié. Nous avons montré que le meilleur traitement d'entretien était le rituximab, surpassant l'effet du méthotrexate ou de l'azathioprine. Durant cette phase, la corticothérapie est arrêtée ou donnée à très petite dose. Dans la granulomatose éosinophilique avec polyangéite (GEPA), la stratégie est un peu différente et les essais prospectifs manquent pour démontrer l'intérêt du rituximab ou du mépolizumab (anti-IL5) en induction de la rémission. En traitement d'entretien, une corticothérapie prolongée (par voie orale et/ou inhalée) est souvent nécessaire pour contrôler la maladie asthmatique. Seul le mépolizumab a montré sa capacité à prévenir les rechutes et à réduire la dose de corticoïdes contrôlant l'asthme. Les questions actuelles que pose le traitement d'entretien sont notamment sa durée qui pourrait être variable et adaptée au risque de rechute et les risques induits par l'immunodépression prolongée, notamment infectieux.

The current state-of-the-art in pharmacotherapy for pulmonary sarcoidosis.

INTRODUCTION: Sarcoidosis is a chronic granulomatous of unknown etiology that mostly affects lungs with an heterogenous clinical presentation and prognosis. Therefore, therapeutic management of the disease is challenging. The goals of treatment are to prevent or to minimize organ damage, to relieve symptoms, and to improve the patient's quality of life. AREAS COVERED: The present review covers current pharmacotherapy options for pulmonary sarcoidosis. Corticosteroids are still the first-line treatment option, however, for those patients with prolonged expectation of treatment, undesirable side effects and refractory disease, immunosuppressive drugs are preferred options. Biological drugs are promising third line therapies. Recent evidence shows that antifibrotic agents, such as nintedanib, have a role in fibrotic lung disease, as well as efzofitimob, which has shown promising results in controlling inflammatory lung disease. EXPERT OPINION: Sarcoidosis treatment is evolving as new molecules are available. The number of studies of therapies for pulmonary sarcoidosis has increased in recent years, however, the information available is still limited and there is no consensus on how to monitor the activity of the disease.

A multicenter study of long-term outcomes of relapsing polychondritis in Iran.

Relapsing polychondritis (RP) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RP may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RP in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RP induced damage. A total of 29 patients with RP were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RP outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing-remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RP induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RP induced damage. Long-term remission and medications-free remission in RP is accessible. However, RP related damage occur in majority of patients.

Clinical characteristics of a COVID-19 cohort treated at UCLA Ronald Reagan Medical Center during the breaking phase of the pandemic: A retrospective study.

To this date, COVID-19 remains an unresolved pandemic, and the impairment of redox homeostasis dictates the severity of clinical outcomes. Here we examined initial UCLA cohort of 440 COVID-19 patients hospitalized between March 1st and April 1st, 2020, representing the first wave of the pandemic. The mean age was 58.88 ± 21.12, among which males were significantly more than females (55.5 % vs. 44.5 %), most distinctively in age group of 50-69. The age groups of 50-69 (33.6 %) and ≥70 (34.8 %) dominated. The racial composition was in general agreement with Census data with slight under-representation of Hispanics and Asians, and over-representation of Caucasians. Smoking was a significant factor (28.8 % vs. 11.0 % in LA population), likewise for obesity (BMI ≥30) (37.4 % vs. 27.7 % in LA population). Patients suffering from obesity or BMI<18.5 checked into ICU at a significantly higher rate. A 74.5 % of the patients had comorbidities including diabetes, chronic kidney disease, chronic pulmonary disease, congestive heart failure and peripheral vascular disease. The levels of d-dimer were drastically upregulated (1159.5 ng/mL), indicating hypercoagulative state. Upregulated LDH (328 IU/L) indicated significant tissue damages. A distorted redox hemeostasis is a common trait associated with these risk factors and clinical markers. A quarter of the patients received antivirals, among which Remdesivir most prescribed (23.6 %). Majority received antithrombotics (75 %), and antibiotics. Upon admission, 67 patients were intubated or received CPR; 177 patients eventually received intensive care (40.2 %). While 290 were discharged alive, 10 remained hospitalized, 73 were transferred, and 36 died with 3 palliatively discharged. In summary, our data fully characterized a Californian cohort of COVID-19 at the breaking phase of the pandemic, indicating that population demographics, biophysical characters, comorbidities and molecular pathological parameters have significant impacts on the evolvement of a pandemic. These provide critical insights into effective management of COVID-19, and future break from another pathogen.

Healthcare resource utilization patterns in psoriasis patients using biologic and conventional treatments in Finland.

Introduction and aim: Psoriasis vulgaris is associated with a significant healthcare burden, which increases over time as the disease progresses. The aim of this retrospective, population-based registry study was to characterize healthcare resource utilization (HCRU) in patients with psoriasis using biologics and oral immunosuppressants (conventionals) in Finland. Materials and methods: The study cohort included all patients with a diagnosis of psoriasis vulgaris in the secondary healthcare setting between 2012-2018, who initiated a biologic (n=1,297) or conventional (n=4,753) treatment between 2013-2017. Data on primary and secondary HCRU were collected from nationwide healthcare registries. Results: The results indicated a remarkable decrease in contacts with a dermatologist after the treatment initiation among patients starting biologic (mean annual number of contacts 5.4 per person before and 2.3 after the initiation), but not conventional (3.3 and 3.2) treatment. For conventional starters there was a high level of contacts with a dermatologist surrounding times of treatment switching, which was not observed for biologic starters. Conclusion: Overall, primary and other secondary care contacts did not decrease after the initiation or switch of treatment. The results highlight the importance of thorough consideration of the most optimal treatment alternatives, considering the overall disease burden to patients and healthcare systems.

Nanoparticle-hydrogel composite as dual-drug delivery system for the potential application of corneal graft rejection.

Immune rejection remains the major cause of corneal graft failure. Immunosuppressants (such as rapamycin; RAPA) adjunctive to antibiotics (such as levofloxacin hydrochloride; Lev) are a clinical mainstay after corneal grafts but suffer from poor ocular bioavailability associated with severe side effects. In this study, we fabricated a Lev@RAPA micelle loaded cationic peptide-based hydrogel (NapFFKK) as a dual-drug delivery system by integrating RAPA micelles with Lev into a cationic NapFFKK hydrogel to potentially reduced the risk of corneal graft rejection. The properties of the resulting hydrogels were characterized using transmission electronmicroscopy and rheometer. Lev@RAPA micelles loaded NapFFKK hydrogel provided sustained in vitro drug release without compromising their inherent pharmacological activities. Topical instillation of Lev@RAPA micelles loaded NapFFKK hydrogel resulted in the great ocular tolerance and extended precorneal retention over 60 min, thus significantly enhancing the ocular bioavailability of both Lev and RAPA. Overall, such dual-drug delivery system might be a promising formulation for the suppression of corneal graft failure.

Comparison of whole-blood sirolimus concentrations measured by EMIT-based Siemens Viva-ProE® System and LC-MS/MS in Chinese transplant patients.

Sirolimus (SRL) is commonly used in transplant patients to prevent organ transplant rejection. The current guidelines recommend to perform SRL therapeutic drug monitoring regularly to improve treatment outcomes and avoid adverse effects. Consequently, a precise and accurate method for determining SRL is crucial in clinical practice. Currently, liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunoassays have been widely adopted for determining SRL concentrations. However, previous studies have shown that immunoassays exhibit a positive bias compared to LC-MS/MS. As the new updated version of the EMIT-based Viva-E® System (SVPS), this study aims to compare SRL blood concentrations measured by the SVPS and LC-MS/MS. The residual whole-blood samples obtained from transplant patients were simultaneously analyzed using the SVPS and LC-MS/MS, respectively. The correlation between the two assays was analyzed using the linear regression analysis and Deming linear regression. The Pearson correlation coefficient and Intraclass correlation coefficient (ICC) analysis were executed. The Paired Wilcoxon test and Bland-Altman analysis were performed to assess the concordance between the two methods. The SVPS considerably increased SRL concentration value by 46.62 % as compared to the LC-MS/MS method. When SRL concentrations measured by the SVPS were above 4.0 ng/mL, there was no significant difference between the corrected SVPS concentrations after using the Deming linear regression equation, indicating their interchangeability. Given the significant disparities observed between EMIT and LC-MS/MS, it is crucial to indicate the methodology and instruments in both TDM reports and future clinical guidelines. Our study also provides the conversion formulas between the SVPS and LC-MS/MS, which can be applied as a reference for different clinical centers.

Clinical and humoral response after SARS-CoV-2 breakthrough infection in patients receiving immunosuppressant therapy.

BACKGROUND: Despite impaired humoral response in patients treated with immunosuppressants (ISPs), recent studies found similar severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection compared to controls. One potential explanation is the rapid generation of humoral response on infection, but evidence is lacking. OBJECTIVES: We investigated the longitudinal dynamics of the SARS-CoV-2 antibody repertoire after SARS-CoV-2 delta and omicron breakthrough infection in patients with immune-mediated inflammatory diseases (IMIDs) receiving ISP therapy and controls. METHODS: As a prospective substudy of the national Target-to-B! (T2B!) consortium, we included IMID patients receiving ISPs therapy and controls who reported SARS-CoV-2 breakthrough infection between July 1, 2021, and April 1, 2022. To get an impression of the dynamics of the antibody repertoire, 3 antibody titers of wild-type RBD, wild-type S, and omicron RBD were measured at 4 time points after SARS-CoV-2 breakthrough infection. RESULTS: We included 302 IMID patients receiving ISPs and 178 controls. Antibody titers increased up to 28 days after breakthrough infection in both groups. However, in IMID patients receiving therapy with anti-CD20 and sphingosine-1 phosphate receptor modulators, antibody titers were considerably lower compared to controls. In the anti-TNF group, we observed slightly lower antibody titers in the early stages and a faster decline of antibodies after infection compared to controls. Breakthrough infections were mostly mild, and hospitalization was required in less than 1% of cases. CONCLUSIONS: Most ISPs do not influence the dynamics of the SARS-CoV-2 antibody repertoire and exhibit a rapid recall response with cross-reactive antibody clones toward new virus variants. However, in patients treated with anti-CD20 therapy or sphingosine-1 phosphate receptor modulators, the dynamics were greatly impaired, and to a lesser extent in those who received anti-TNF. Nevertheless, only a few severe breakthrough cases were reported.

Oral Prescription Management.

The treatment of atopic dermatitis (AD) with oral treatments has been limited in the past due to the increased risk of adverse effects associated with oral agents. However, in recent years, a shift toward the minimization of adverse effects has been explored. Although existing treatment options like oral corticosteroids and Immunosuppressive therapies have been utilized for acute flare-ups of AD, their long-term use is limited by adverse effects and the need for lab monitoring. New systemic treatment options such as Janus kinase (JAK) inhibitors are emerging as a promising therapy, due to their quick onset and antipruritic features. However, the black box warning associated with this medication class requires careful selection of appropriate candidates and patient education despite early favorable safety profiles seen in AD trials. Discussion of other oral agents, like antibiotics and antihistamines, and their role in AD management are also clarified.