Radiological presentation of active pulmonary tuberculosis in kidney transplant recipients: a retrospective study of four cases and a review of the literature.

Although kidney transplantation is the best therapeutic option for patients with chronic kidney disease, the immunosuppression required greatly increases susceptibility to infections that are responsible for high post-transplant mortality. Pulmonary tuberculosis (TB) represents a major cause of such infections, and its early diagnosis is therefore quite important. In view of that, we researched the manifestations of active pulmonary TB in kidney transplant recipients, through chest X-ray and computed tomography (CT), as well as determining the number of cases of active pulmonary TB occurring over a 3.5-year period at our institution. We identified four cases of active pulmonary TB in kidney transplant recipients. The CT scans provided information complementary to the chest X-ray findings in all four of those cases. We compared our CT findings with those reported in the literature. We analyzed our experience in conjunction with an extensive review of the literature that was nevertheless limited because few studies have been carried out in lowand middle-income countries, where the incidence of TB is higher.

Apesar de o transplante renal ser a melhor opção terapêutica para pacientes com doença renal crônica, a imunodepressão decorrente desse tratamento eleva muito a suscetibilidade desses pacientes a infecções, responsáveis por altas taxas de mortalidade pós-operatórias. A tuberculose (TB) pulmonar é uma significativa causa dessas infecções, sendo muito importante o seu diagnóstico precoce. Assim, nós pesquisamos as manifestações da TB pulmonar ativa nessa população de transplantados renais por meio de radiografias simples e tomografia computadorizada (TC) do tórax, também para estabelecer o número de casos de TB pulmonar ativa em nossa instituição após levantamento de 3,5 anos. Encontramos quatro casos de TB pulmonar ativa em pacientes transplantados renais. A TC forneceu informações adicionais em relação às radiografias de tórax em 100% dos casos analisados. Comparamos os nossos achados de TC com os relatados na literatura. Somamos a experiência obtida com extensa revisão da literatura, ainda limitada nessa questão, com poucos estudos realizados em países em desenvolvimento onde a incidência de TB é maior.

Relevance of Tacrolimus Trough Concentration and Hepatitis E virus Genetic Changes in Kidney Transplant Recipients With Chronic Hepatitis E.

Introduction: Hepatitis E virus (HEV) can cause chronic infection (≥3 months) and cirrhosis in immunocompromised patients, especially kidney transplant recipients. Low alanine aminotransferase (ALT) levels and high HEV intrahost diversity have previously been associated with evolution toward chronicity in these patients. We hypothesized that additional clinical and viral factors could be associated with the risk of chronic HEV infection. Methods: We investigated a series of 27 kidney transplant recipients with HEV infection, including 20 patients with chronic hepatitis E. Results: High tacrolimus trough concentration at diagnosis was the most relevant marker associated with chronic hepatitis E (9.2 vs. 6.4 ng/ml, P = 0.04). Most HEV genetic changes selected during HEV infection were compartmentalized between plasma and feces. Conclusion: This compartmentalization highlights the diversity and complexity of HEV replication compartments. Tacrolimus trough concentration at diagnosis of HEV infection could allow an early identification of patients at high risk of chronic hepatitis E and guide treatment initiation.

Survival and Success of Dental Implants in Patients with Autoimmune Diseases: a Systematic Review.

Objectives: The purpose of this systematic review is to disclose the impact of autoimmune diseases and their medical treatment on dental implant survival and success. Material and Methods: A literature search was conducted using MEDLINE (PubMed), The Cochrane Library and Embase up to December 6th, 2021. Any clinical study on patients with an autoimmune disease in whom implant therapy was performed was eligible. The quality of included studies was assessed using the Newcastle-Ottawa Scale. For each autoimmune disease group, data synthesis was divided into three groups: 1) overall results of the autoimmune disease, 2) overall results of corresponding control groups and 3) overall results of the autoimmune disease with a concomitant autoimmune disease (a subgroup of group 1). Descriptive statistics were used. Results: Of 4,865 identified articles, 67 could be included and mainly comprising case reports and retrospective studies with an overall low quality. Implant survival rate was 50 to 100% on patient and implant level after a weighted mean follow-up of 17.7 to 68.1 months. Implant success was sporadically reported. Data on immunosuppressive medication were too heterogeneously reported to allow detailed analysis. Conclusions: Overall, a high implant survival rate was reported in patients with autoimmune diseases. However, the identified studies were characterized by a low quality. No conclusions could be made regarding implant success and the effect of immunosuppressants due to heterogeneous reporting.

Studying Outcomes after Steroid-Sparing Immunosuppressive Agent vs. Steroid-Only Treatment for Immune-Related Adverse Events in Non-Small-Cell Lung Cancer (NSCLC) and Melanoma: A Retrospective Case-Control Study.

BACKGROUND: The effects of steroid-sparing immunosuppressive agents (SSIAs), used for the treatment of immune-related adverse events (irAEs), on immune checkpoint inhibitor (ICI) antitumor activity is not well known. We compared tumor outcomes of patients who received corticosteroid monotherapy (CS) versus a corticosteroid plus SSIA (CS-SSIA) for irAE treatment, using statistical methods to address immortal time bias. METHODS: We conducted a retrospective case-control study on patients ≥ 18 years with melanoma or non-small-cell lung cancer (NSCLC) treated with ≥1 ICI at a quaternary care center between 1 January 2016 and 11 January 2021. Patients were divided into two cohorts: CS or CS-SSIA. We used propensity score nearest-neighbor matching to match on tumor type, stage, and prior lines of therapy. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included the time from the start of the irAE treatment to the irAE resolution. Hazard ratios (HRs) for PFS and OS were calculated using the Cox proportional hazard regression method with both (1) the time to the steroid and SSIA as time-varying covariates and (2) a binary exposure classification not accounting for the time to the treatment. RESULTS: A total of 167 patients were included after matching (132 in the CS cohort and 35 in the CS-SSIA cohort). Sixty-six percent of all the patients had melanoma. The most common irAEs requiring treatment were gastroenterocolitis and hepatitis. In an adjusted analysis not accounting for immortal time bias, there were no significant differences in PFS (HR 0.75, 95% CI [0.46-1.23]) or OS (HR 0.82, 95% CI [0.46-1.47]). In analyses using a time-varying treatment indicator, there was a trend toward improved PFS in patients treated with SSIAs (HR 0.54, CI 0.26-1.10). There was no difference in OS (HR 1.11, CI 0.55-2.23). Patients with melanoma who specifically received infliximab had improved PFS compared to patients with CS only, after adjusting for immortal time bias (HR 0.32, CI 0.24-0.43). CONCLUSIONS: The use of SSIAs with CS did not have worse outcomes than CS monotherapy. In melanoma, our findings showed improved PFS for the use of infliximab versus steroid monotherapy for irAEs. Large, prospective, randomized controlled trials are needed to confirm these findings and guide the optimal treatment of irAEs.

Does Lymphovenous Anastomosis Effect Mammalian Target of Rapamycin Inhibitor-associated Lymphedema Patients?

The mammalian target of rapamycin (mTOR) inhibitors are used to prevent organ transplant rejection and are preferred over other immunosuppressants due to its low nephrotoxicity. However, mTOR inhibitors have been associated with various adverse effects including lymphedema. Although rare in incidence, previously known treatments for mTOR inhibitor-induced lymphedema were limited to discontinuation of related drugs and complex disruptive therapy with variable results. In this article, three patients who developed lymphedema in their lower limbs after using mTOR inhibitors, including two bilateral and one unilateral case, were treated with physiologic surgery methods such as lymphovenous anastomosis (LVA) and lymph node transfer. The efficacy of the treatment was evaluated. In the three cases described, cessation of the drug did not lead to any reduction in edema. The use of LVA and lymph node transfer resulted in early reductions in volume but failed to sustain over time. All patients underwent secondary nonphysiologic surgery such as liposuction resulting in sustained improvement. This series presents the first physiologic approach to mTOR inhibitor-induced lymphedema. Although further study is warranted, the physiologic surgical options may have limited success and nonphysiologic options may offer better sustainable results.

Analysis of clinical characteristics and factors affecting treatment responses in patients with pyoderma gangrenosum: a multicenter study of 239 patients☆.

BACKGROUND: Pyoderma Gangrenosum (PG) is a chronic disease characterized by recalcitrant skin ulcers. OBJECTIVE: We aimed to evaluate the demographic, clinical characteristics, treatments and factors affecting the treatment responses of patients with PG. METHODS: We performed a multicenter study of 12 tertiary care centers. We analyzed the data of the patients who were followed up with a diagnosis of PG between the years 2012‒2022 retrospectively. RESULTS: We included a total of 239 patients of whom 143 were female and 96 were male, with an average age of 54.2 ±â€¯17.4 years. The most common treatment was systemic steroids (n = 181, 75.7%). Among these patients, 50.8% (n = 92) used systemic steroids as the sole systemic agent, while 49.2% (n = 89) used at least one adjuvant immunosuppressive agent. The independent factors determined in regression analysis to influence response to systemic steroids positively were disease onset age ≥ 30-years, negative pathergy, absence of leukocytosis, negative wound culture, presence of a single lesion, and absence of upper extremity involvement. Biological agents were used in 18.4% (n = 44) of the patients in the present study. We also analyzed pathergy positive PG and early onset (onset age < 30) PG separately due to their distinct clinical features which were revealed during statistical analysis. STUDY LIMITATIONS: Retrospective nature of the present study. CONCLUSIONS: Analyses of the factors influencing treatment responses are addressed in this study. Also, we concluded that investigation for accompanying autoinflammatory diseases of pathergy positive PG and early onset PG is necessary and the patients in these two groups are more resistant to treatment, necessitating more complicated treatments.

Real-world pharmacological treatment of pregnant patients with rheumatic diseases from China: a retrospective analysis from 2016 to 2021.

Introduction: We investigated trends in the use of therapeutic drugs for pregnant patients with rheumatic diseases in nine Chinese cities (Beijing, Chengdu, Guangzhou, Harbin, Hangzhou, Shanghai, Shenyang, Tianjin, and Zhengzhou) to provide a reference for drug use in clinic. Methods: Outpatient prescription data for pregnant patients diagnosed with rheumatic diseases in nine cities across China in 2016-2021 were extracted from the Hospital Prescription Cooperation Project of the Hospital Pharmacy Professional Committee of the Chinese Pharmaceutical Association. A retrospective analysis was then performed, incorporating data on patient age, defined daily doses (DDDs), defined daily cost (DDC), and other metrics. Results: In 2016-2020, more than 70% of the pregnant patients diagnosed with rheumatic diseases in these nine cities were 25 to < 35 years of age. The most common rheumatic diseases during pregnancy were antiphospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE). In terms of the routine use of daily therapeutic drugs, the DDDs of low molecular weight heparins (LMWHs), glucocorticoids, and immunosuppressive agents dominated the top three. Intravenous immunoglobulin (IVIG) and tumor necrosis factor inhibitors (TNFi) have been used since 2019 and had been in the forefront of the DDC. Conclusion: The number and total cost of prescriptions for therapeutic drugs of pregnancy complicated by rheumatic diseases, have increased significantly over the study interval. Conventional therapeutic drugs, especially glucocorticoids, LMWHs, and hydroxychloroquine were the most widely used drugs in pregnant patients with rheumatic diseases. However, IVIG and TNFi, relatively high cost, have shown gradual increases in clinical use since 2019.

A hospital management algorithm for acute poisoning by Paraquat® in a pediatric population, a series of cases / Algoritmo de manejo hospitalario para la intoxicación aguda por Paraquat® en población pediátrica, serie de casos.

Paraquat®, or N,N'-dimethyl-4,4'-bipyridinium dichloride, is a bipyridyl compound used as a non-selective herbicide and desiccant that can cause acute poisoning through all routes of exposure. There is no known antidote, and the available treatments are based on avoiding its absorption and timely removing it, in adults and children. We describe a case series of 14 pediatric patients from the department of Cauca, Colombia, with acute intoxication after oral intake of paraquat. Patients were referred to a medium-high complexity hospital in southwestern Colombia and treated according to an institutional protocol for acute paraquat poisoning. Acute paraquat poisoning after oral ingestion is associated with a high mortality rate, even with timely medical attention, as the compound has no known antidote and quickly reaches systemic concentrations for fulminant poisoning. Based on the available literature, our center has proposed a clinical protocol including early standard management, immunosuppressive and antioxidant treatments, and systemic removal techniques. This protocol suggests an adequate approach to acute paraquat poisoning in the pediatric population.

El dicloruro de 1,1'-dimetil-4,4'-bipiridilo (Paraquat®) es un compuesto químico de la familia de las piridinas, utilizado como herbicida no selectivo y desecante. Este compuesto puede causar intoxicación aguda por todas las vías de exposición. En el momento, no hay un antídoto conocido y los tratamientos disponibles, incluidos los pediátricos, se basan en contrarrestar su absorción y propiciar su remoción oportuna. Se describe una serie de casos de 14 pacientes pediátricos, procedentes en su mayoría del departamento del Cauca, con intoxicación aguda por ingestión de paraquat. Los pacientes fueron remitidos y atendidos en un hospital de mediana a alta complejidad en el suroccidente colombiano, con un protocolo institucional para el manejo de la intoxicación aguda por el herbicida. La intoxicación aguda con paraquat por vía oral se asocia con una alta tasa de mortalidad, aún con atención médica oportuna, pues fácilmente se alcanzan concentraciones sistémicas para ser fulminante. Basado en la literatura disponible, el Hospital Universitario San José ha propuesto un protocolo clínico ­adecuado para la intoxicación aguda por paraquat en población pediátrica­ que incluye manejo estándar temprano, tratamiento inmunosupresor y antioxidante, y técnicas para su remoción sistémica.

Approaches Towards Better Immunosuppressive Agents.

Several classes of compounds are applied in clinics due to their immunosuppressive properties in transplantology and the treatment of autoimmune diseases. Derivatives of mycophenolic acid, corticosteroids and chemotherapeutics bearing heterocyclic moieties like methotrexate, azathioprine, mizoribine, and ruxolitinib are active substances with investigated mechanisms of action. However, improved synthetic approaches of known drugs and novel derivatives are still being reported to attempt better accessibility and therapeutic properties. In this review article, we present the synthesis of the designed chemical structures based on recent literature reports concerning novel compounds as promising immunosuppressive drugs. Moreover, some of the discussed derivers revealed also other types of activities with prospective medicinal potential.

The Balance Between Intensive and Palliative Care in an Anti-melanoma Differentiation-Associated Gene 5 (MDA5) Antibody-Positive Acute Interstitial Pneumonia in a Nonagenarian: A Case Report.

This case report details the management of anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive acute interstitial pneumonia in a 93-year-old man, a condition characterized by rapid progression and high mortality. Despite the grim prognosis typically associated with this disease, especially in elderly patients, the subject of this report survived beyond the expected timeframe, illustrating the effectiveness of prompt and aggressive treatment strategies. Initially presenting with dyspnea, the patient's diagnostic process was challenging due to the absence of dermatomyositis (DM)-specific skin manifestations. However, early suspicion led to the identification of anti-MDA5 antibodies, confirming the diagnosis. The treatment regimen initiated with corticosteroid pulses, cyclophosphamide, tacrolimus, and high-dose gamma globulin therapy significantly improved the patient's respiratory conditions, giving the patient and his family time to decide on their palliative care. This approach underlines the importance of early diagnosis and the implementation of comprehensive treatment strategies in managing anti-MDA5 antibody-positive interstitial pneumonia. In this case, the successful outcome adds valuable insights into the potential for extending survival and enhancing the quality of life in elderly patients with this severe autoimmune condition, emphasizing the need for a proactive and aggressive approach to treatment.

Complete remission of giant cell myocarditis by prednisolone monotherapy: A case with mild inflammation demonstrated by mismatch between T2-high intensity areas and late gadolinium enhancement.

Giant cell myocarditis (GCM) is a potentially lethal subtype of myocarditis. Herein, we report a case of a 22-year-old woman with GCM who was successfully treated with prednisolone monotherapy. The patient had a fever and shortness of breath and was referred to our hospital. Laboratory test results revealed elevated troponin I levels. Cardiac magnetic resonance (CMR) showed high intensity in the inferoseptal segment of the left ventricle on T2-weighted short tau inversion recovery imaging without late gadolinium enhancement (LGE), suggesting predominant edema rather than necrosis. The patient was diagnosed with GCM based on an endomyocardial biopsy, which revealed lymphocyte infiltration and multinucleated giant cells in the absence of granuloma formation. Subsequently, the patient received intravenous methylprednisolone at 1000 mg/day for 3 days followed by oral prednisolone at 30 mg/day, which normalized troponin levels. Follow-up CMR revealed improved cardiac inflammation; therefore, the patient was discharged without prescribing another immunosuppressive agent. Prednisolone was tapered and terminated three years after discharge. The patient went one year without medication and had no recurrence of GCM on follow-up. This case highlights the presence of mild GCM, successfully treated by steroid monotherapy, in which the mismatch between high-intensity T2 areas and LGE suggests mild inflammation. Learning objective: Giant cell myocarditis (GCM) is potentially lethal and usually requires multiple immunosuppressive agents. Here, we report a patient with GCM with preserved left ventricular ejection fraction. Cardiac magnetic resonance revealed focal high T2 signal intensity areas without late gadolinium enhancement, indicating myocardial edema without necrosis. The patient remained in remission with prednisolone monotherapy for 2 years. Our report indicates that "mild" GCM may be treated with prednisolone monotherapy.

Identifying pregnancy episodes and estimating the last menstrual period using an administrative database in Korea: an application to patients with systemic lupus erythematosus.

OBJECTIVES: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE). METHODS: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients. RESULTS: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy. CONCLUSIONS: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

Acute pancreatitis as a complication of acute COVID-19 in kidney transplant recipients.

BACKGROUND: Acute pancreatitis is a rare extrapulmonary manifestation of coronavirus disease 2019 (COVID-19) but its full correlation with COVID-19 infection remains unknown. AIM: To identify acute pancreatitis' occurrence, clinical presentation and outcomes in a cohort of kidney transplant recipients with acute COVID-19. METHODS: A retrospective observational single-centre cohort study from a transplant centre in Croatia for all adult renal transplant recipients with a functioning kidney allograft between March 2020 and August 2022 to record cases of acute pancreatitis during acute COVID-19. Data were obtained from hospital electronic medical records. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was proven by a positive SARS-CoV-2 real-time reverse transcriptase-polymerase chain reaction on the nasopharyngeal swab. RESULTS: Four hundred and eight out of 1432 (28.49%) patients who received a renal allograft developed COVID-19 disease. The analyzed cohort included 321 patients (57% males). One hundred and fifty patients (46.7%) received at least one dose of the anti-SARS-CoV-2 vaccine before the infection. One hundred twenty-five (39.1%) patients required hospitalization, 141 (44.1%) developed pneumonia and four patients (1.3%) required mechanical ventilation. Treatment included immunosuppression modification in 233 patients (77.1%) and remdesivir in 53 patients (16.6%), besides the other supportive measures. In the study cohort, only one transplant recipient (0.3%) developed acute pancreatitis during acute COVID-19, presenting with abdominal pain and significantly elevated pancreatic enzymes. She survived without complications with a stable kidney allograft function. CONCLUSION: Although rare, acute pancreatitis may complicate the course of acute COVID-19 in kidney transplant recipients. The mechanism of injury to the pancreas and its correlation with the severity of the COVID-19 infection in kidney transplant recipients warrants further research.

Evaluation of SARS-CoV-2 Vaccine-Induced Antibody Responses in Patients with Neuroimmunological Disorders: A Real-World Experience.

This study evaluates the antibody responses to SARS-CoV-2 vaccines in patients with neuroimmunological disorders (pwNID) who are receiving immunomodulating treatments, compared to healthy individuals. It included 25 pwNID with conditions such as optic neuritis, neuromyelitis optica spectrum disorder, multiple sclerosis, myasthenia gravis, and polymyositis, as well as 56 healthy controls. All participants had completed their full SARS-CoV-2 vaccination schedule, and their blood samples were collected within six months of their last dose. The concentration of anti-SARS-CoV-2 IgG antibodies was measured using an enzyme-linked immunosorbent assay. The results showed that pwNID had significantly lower antibody titers (58.4 ± 49.2 RU/mL) compared to healthy individuals (81.7 ± 47.3 RU/mL). This disparity persisted even after adjusting for age and the interval between the final vaccination and sample collection. A notable correlation was found between the use of immunomodulating treatments and reduced antibody levels, whereas mRNA vaccines were linked to higher antibody concentrations. The conclusion of this study is that immunomodulating treatments may reduce the effectiveness of SARS-CoV-2 vaccines in pwNID. This insight is crucial for healthcare providers in designing vaccination strategies and managing treatment plans for pwNID on immunomodulating therapies, highlighting the need for personalized approaches in this subgroup.

Immune outcomes of lung transplant recipients with different cytochrome P450 3A5 phenotypes after discontinuation of voriconazole antifungal prophylaxis.

INTRODUCTION: Tacrolimus forms the backbone of immunosuppression regimens in lung transplant recipients (LTRs). It is extensively metabolized by cytochrome P450 (CYP) 3A5 enzymes, of which polymorphisms can significantly affect tacrolimus dose requirements. It is unknown how coadministration of tacrolimus with voriconazole, a potent CYP3A5 inhibitor, affects rejection rates or empiric dose adjustments needed after voriconazole discontinuation. METHODS: This retrospective cohort study compares LTRs with poor (PR) versus intermediate/extensive (IE) CYP3A5 metabolizer phenotypes. The primary endpoint is cumulative immune outcomes within three months of voriconazole discontinuation; secondary endpoints include change in tacrolimus dose-to-concentration ratios after voriconazole discontinuation. RESULTS: Thirty-four patients underwent full analysis: 13 IE and 21 PR metabolizers. A higher proportion of IE metabolizers were African American (46.2% vs. 9.5%, p = .03). There was no significant difference in composite immune outcomes, though there was a proportionally higher frequency of new donor-specific antibody development in PR metabolizers (14.3% vs 7.7%, p = .56). Both groups required approximately 2.5 to 3-fold tacrolimus dose increases post-voriconazole discontinuation to re-attain therapeutic levels. CONCLUSION: This novel investigation sheds light on how CYP3A5 phenotype could be used to guide tacrolimus dosing, with the goal of preventing both toxicity and organ rejection.

Association between the time of initial relapse and subsequent relapses in patients with childhood-onset idiopathic nephrotic syndrome.

BACKGROUND: Nephrotic syndrome relapse within 6 months is a known risk factor for steroid-dependent nephrotic syndrome/frequently relapsing nephrotic syndrome (SDNS/FRNS), but the risk of early development of SDNS/FRNS and initiation of immunosuppression therapy remains unknown. METHODS: Patients with childhood-onset idiopathic nephrotic syndrome who had the first relapse within 6 months were enrolled. We analyzed the relationship between the time of the first relapse or the time of initial remission and incidence of SDNS/FRNS or initiation of immunosuppression therapy. RESULTS: Forty-five patients were enrolled. Twenty out of 23 patients (87%) with the first relapse within 30 days after discontinuing initial steroid therapy experienced a second relapse within 30 days after discontinuing steroid therapy. Additionally, most patients in this group (96%) experienced a second relapse within 6 months after the onset and were diagnosed as SDNS/FRNS at this time. In this group, the incidence of SDNS/FRNS development within 6 months was 96%. In contrast, the incidence of SDNS/FRNS development within 6 months was 18% in patients with the first relapse more than 30 days after steroid discontinuation. The incidence of initiation of immunosuppressive agents within 6 months was 83% in the former group and 14% in the latter group. CONCLUSIONS: Most patients with the first relapse within 30 days after discontinuing steroid therapy developed SDNS/FRNS and were administered immunosuppressive agents within 6 months. Thus, it might be reasonable to start immunosuppression therapy in this group without waiting for the second relapse.

A Real-World Study of Steroid-Free Monotherapy with Tofacitinib in Severe and Therapy-Recalcitrant Alopecia Areata, Alopecia Totalis, and Alopecia Universalis Cases: A Retrospective Analysis.

Background: Alopecia areata (AA) presents with noncicatricial alopecia and has multifactorial etiology. Janus Kinase inhibitors (JAKibs) with potential efficacy and favorable side-effect profile are the first class of drugs to receive FDA approval in AA. Objectives: Our primary objective was to assess the complete response rates to tofacitinib monotherapy in severe and recalcitrant AA, alopecia totalis (AT), and alopecia universalis (AU) patients using the latest percentage change in Severity of alopecia tool (SALT) score. We also aimed to analyze the various systemic agents used by these patients prior to the use of tofacitinib. Materials and Methods: Institutional records of 17 patients with severe or refractory AA, AT, and AU treated with tofacitinib monotherapy were analyzed, retrospectively. The response to tofacitinib therapy was determined after calculating percentage change in SALT score. End of treatment was defined as the dose which resulted in a significant response (complete/near complete response was ≥75% hair regrowth from baseline as determined by SALT score). Results: Majority of patients had severe AA (SALT ≥ 50) (n = 9/17, 52.94%), while five patients had AT and three had AU. All patients had received either systemic glucocorticoids (GCS), which included oral mini pulse (OMP) (n = 8), intravenous pulse steroids (n = 4), and daily oral GCS (n = 6) or immunosuppressive agents (ISAs) which included cyclosporine (n = 14) followed by methotrexate (n = 6) and azathioprine (n = 6). Mean SALT score prior to starting tofacitinib was 74.23. Mean dose of tofacitinib used was 13.23 mg (10-15 mg) and mean duration of treatment was 9.23 months. Latest percentage change of SALT score ranged from 70.58% to 100%, with an average of 91.47%. Most patients showed complete/near complete response (13/17, 76.47%). Conclusion: Tofacitinib was found to be safe and effective in severe/refractory AA, AU, and AT patients recalcitrant to other treatment modalities in our study. Further studies are needed to assess the effect of these targeted drugs on JAK-STAT expression or tissue cytokines involved in the pathogenesis of AA using immunohistochemistry.

A qualitative study of facilitators of medication adherence in systemic lupus erythematosus: Perspectives from rheumatology providers/staff and patients.

OBJECTIVE: Systemic lupus erythematosus (SLE) disproportionately affects patients from racial and ethnic minority groups. Medication adherence is lower among these patient populations, and nonadherence is associated with worse health outcomes. We aimed to identify factors that enable adherence to immunosuppressive medications among patients with SLE from racial and ethnic minority groups. METHODS: Using a qualitative descriptive study design, we conducted in-depth interviews with purposefully selected (1) patients with SLE from racial and ethnic minority groups who were taking immunosuppressants and (2) lupus providers and staff. We focused on adherence facilitators, asking patients to describe approaches supporting adherence and for overcoming common adherence challenges and providers and staff to describe actions they can take to foster patient adherence. We used applied thematic analysis and categorized themes using the Capability, Opportunity, Motivation, Behavior (COM-B) model. RESULTS: We interviewed 12 patients (4 adherent and 8 nonadherent based on medication possession ratio) and 12 providers and staff. Although each patient described a unique set of facilitators, patients most often described social support, physical well-being, reminders, and ability to acquire medications as facilitators. Providers also commonly mentioned reminders and easy medication access as facilitators as well as patient education/communication and empowerment. CONCLUSION: Using an established behavioral change model, we categorized a breadth of adherence facilitators within each domain of the COM-B model while highlighting patients' individual approaches. Our findings suggest that an optimal adherence intervention may require a multi-modal and individually tailored approach including components from each behavioral domain-ensuring medication access (Capability) and utilizing reminders and social support (Opportunity), while coupled with internal motivation through improved communication and empowerment (Motivation).

Non-Infectious Uveitis and Pregnancy, is There an Optimal Treatment? Uveitis Course and Safety of Uveitis Treatment in Pregnancy.

In pregnancy, a plethora of factors causes changes in maternal immunity. Uveitis flare-ups are more frequent in the first trimester and in undertreated patients. Management of non-infectious uveitis during pregnancy remains understudied. A bibliographic review to consolidate existing evidence was performed by a multidisciplinary group of Ophthalmologists, Gynaecologists and Rheumatologists. Our group recommends initial management with minimum-required doses of corticosteroids, preferably locally, to treat intraocular inflammation whilst ensuring good neonatal outcomes. If ineffective, clinicians should consider addition of Cyclosporine, Azathioprine or Certolizumab pegol, which are seemingly safe in pregnancy. Other therapies (such as Methotrexate, Mycophenolate Mofetil and alkylating agents) are teratogenic or have a detrimental effect on the foetus. Furthermore, careful multidisciplinary preconception discussions and close follow-up are recommended, monitoring for flare-ups and actively tapering medication doses, with a primary endpoint focused on protecting ocular tissues from inflammation, whilst giving minimal risk of poor pregnancy and foetal outcomes.

Measuring treatment adverse event burden in myasthenia gravis: Single-center prospective evaluation utilizing the Adverse Event Unit (AEU).

INTRODUCTION/AIMS: We developed a patient- and physician-weighted consensus unit called the adverse event unit (AEU) that quantifies and compares adverse event (AE) burden among any group of medications in neurological patients. In this study we evaluated preliminary validity and feasibility of measuring AE burden with the AEU in myasthenia gravis (MG). METHODS: This is a single-center, prospective, 1-year, observational study of adult MG patients presenting for routine care between April 1, 2021 and March 31, 2022. The MG Activities of Daily Living (MG-ADL), the 15-item MG Quality of Life revised (MG-QOL15r), MG-Composite, and AEU scores were obtained at all visits. A priori primary feasibility metric was AEU completion rate equal to (within 3.8%, one-sided 95% confidence interval [CI]) or better than MG-ADL completion rate. Time to administer AEU and MG-ADL/MG-QOL15r, correlation between AEU total score and MG-QOL15r, and median AEU scores for each MG medication were evaluated. RESULTS: Fifty-four patients completed 67 study visits; side effects were reported at 75% of the visits. The study met the primary feasibility endpoint; AEU and MG-ADL were recorded at all visits. Times to administer the AEU (median 5 minutes) and MG-ADL/MG-QOL15r were similar. We observed a weak correlation of 0.29 (95% CI 0.03 to 0.51, P = .032) between AEU and MG-QOL15r scores. Non-statistically significant differences in median AEU scores were observed among MG medications. DISCUSSION: Our data demonstrate preliminary feasibility and validity of using the AEU to measure AE burden in MG. Future studies will compare AE burden among MG treatments and evaluate clinically meaningful AEU scores in MG.