Therapeutic modalities and clinical outcomes in a large cohort with LRBA deficiency and CTLA4 insufficiency.

BACKGROUND: LPS-responsive beige-like anchor (LRBA) deficiency (LRBA-/-) and cytotoxic T-lymphocyte-associated antigen-4 (CTLA4) insufficiency (CTLA4+/-) are mechanistically overlapped diseases presenting with recurrent infections and autoimmunity. The effectiveness of different treatment regimens remains unknown. OBJECTIVE: Our aim was to determine the comparative efficacy and long-term outcome of therapy with immunosuppressants, CTLA4-immunoglobulin (abatacept), and hematopoietic stem cell transplantation (HSCT) in a single-country multicenter cohort of 98 patients with a 5-year median follow-up. METHODS: The 98 patients (63 LRBA-/- and 35 CTLA4+/-) were followed and evaluated at baseline and every 6 months for clinical manifestations and response to the respective therapies. RESULTS: The LRBA-/- patients exhibited a more severe disease course than did the CTLA4+/- patients, requiring more immunosuppressants, abatacept, and HSCT to control their symptoms. Among the 58 patients who received abatacept as either a primary or rescue therapy, sustained complete control was achieved in 46 (79.3%) without severe side effects. In contrast, most patients who received immunosuppressants as primary therapy (n = 61) showed either partial or no disease control (72.1%), necessitating additional immunosuppressants, abatacept, or transplantation. Patients with partial or no response to abatacept (n = 12) had longer disease activity before abatacept therapy, with higher organ involvement and poorer disease outcomes than those with a complete response. HSCT was performed in 14 LRBA-/- patients; 9 patients (64.2%) showed complete remission, and 3 (21.3%) continued to receive immunosuppressants after transplantation. HSCT and abatacept therapy gave rise to similar probabilities of survival. CONCLUSIONS: Abatacept is superior to immunosuppressants in controlling disease manifestations over the long term, especially when started early, and it may provide a safe and effective therapeutic alternative to transplantation.

Determinants and characteristics of tuberculosis in liver transplant recipients

Background/aim: Solid organ transplant (SOT) recipients have increased risk of tuberculosis (TB). We aimed to investigate the prevalence and features of TB in liver transplant (LT) recipients at our transplantation canter. Materials and methods: All patients who underwent LT between January 2004 and December 2013 and whose data were accessible were included in the study. Demographic features, tuberculin skin test (TST) results, and TB prevalence were recorded. Characteristics of LT recipients who developed TB were evaluated. Results: A total of 403 patients underwent LT during this period. Mean age was 47.27 ± 11.04 years; 280 (69.47%) were males. The TST was administered to 108 (25.91%) and the QuantiFERON-TB test to 1 patient. TST positivity was determined in 28 (25.93%). Latent TB infection (LTBI) treatment was not recommended to any of the LT candidates. In the posttransplant period, 5 patients (1.24%) developed TB over a median duration of 14 (min: 7, max: 84) months, 2 of whom were found to have had LTBI in the pretransplant period. Conclusion: The prevalence of TB in LT recipients at our center was similar to that in the current literature. LTBI screening, including risk factor assessment and TST/QuantiFERON-TB testing, is necessary in the early diagnostic workup for TB in LT recipients.

[Effectiveness of mepolizumab in patients with severe eosinophilic asthma: In a real life study]. / Agir eozinofilik astimli hastalarda mepolizumab etkinligi: Bir gerçek yasam çalismasi.

Introduction: We analyzed the effects of mepolizumab treatment on symptoms, asthma attacks, pulmonary function test parameters peripheral blood eosinophil level, and percentage in patients with severe eosinophilic asthma receiving mepolizumab treatment as the baseline, sixth and twelfthmonth data. Materials and Methods: The medical records of patients diagnosed with severe eosinophilic asthma and treated with mepolizumab at our clinic were retrospectively reviewed for the period between January 2018 and December 2021. Demographic data of the patients, duration of asthma disease, comorbidities such as a nasal polyp, eosinophilic granulomatous polyangiitis, and nonsteroidal anti-inflammatory drug exacerbated respiratory disease were investigated. A comparison was made of various factors before initiating mepolizumab treatment, as well as at the sixth and twelfth month after treatment initiation. These factors include asthma control test scores, frequency of asthma attacks (including emergency admissions, hospitalizations, and intensive care admissions), peripheral blood eosinophil levels and percentages, and pulmonary function test parameters. Clinic and laboratory parameters that provide a prediction of being a responder and super responder were evaluated. Result: A total of 21 patients were included in the study. Their mean age was 50.7 ± 11.9 years, and four (19%) were males. The mean duration of asthma diagnosis was 17.5 ±13.7 years. 14 patients (66.7%) were atopic. 4 patients (19%) had nasal polyps and four patients (19%) had NERD. Before mepolizumab, 13 (61.9%) patients had received omalizumab. The duration of receiving mepolizumab treatment was 29.2 ± 9.9 months. A statistically significant decrease was observed in both the number and percentage of eosinophils at months six and 12 (p<0.01). There was a statistically significant increase in FEV1 values both as a percentage and in milliliters at month 12. There was an increase in both percentage and milliliters in FEF25-75 values, but this increase did not reach statistical significance. There was a decrease in service admissions, intensive care admissions, and emergency admissions due to asthma exacerbations. Out of 21 patients, 11 (52.4%) were classified as responders, while 10 (47.6%) were classified as super responders. Conclusions: Although the number of patients in our study was limited, mepolizumab improved symptom scores in severe eosinophilic asthma, reduced the number of attacks, and improved pulmonary function test values.

Drug hypersensitivity in drug-resistant tuberculosis.

Objective: To evaluate drug resistant tuberculosis patients who developed drug hypersensitivity to antituberculosis drug. Methods: This was a retrospective study. The primary aim of the study is to determine the demographic and clinical characteristics of patients who develop drug hypersensitivity in drug resistant tuberculosis patients. The secondary aim of the study is to examine the treatment results. Demographic features, tuberculosis diagnostic indicator, clinical signs of developing hypersensitivity reaction, reaction time, and treatment were evaluated. Results: A total of 25 patients were included in the study. The prevalence of hypersensitivity in drug resistance patients was 11.9%. Twelve (48%) of the cases were women. Mean age (mean ± SD) was 37.24 ± 14.44 years; early type hypersensitivity reaction in 13 (52%). Three patients were isoniazid resistant; 19 patients were multidrug-resistant (MDR); 2 patients were pre-extensive drug resistant (Pre-XDR), 1 patient was extensive drug resistance (XDR) tuberculosis. The most common skin findings were maculopapular eruption and urticaria. But also we had seen isole angiodema, urticaria and angioedema, erythema multiforme, lichenoid drug eruption and drug rash with eosinophilia and systemic symptoms. In patients who developed a hypersensitivity reaction, the responsible agent was identified in 14 cases in total. Among the drugs, pyrazinamide, ethambutol, moxifloxacin, amikacin, para amino salicylic, prothionamide, and cycloserine are the responsible agents. When evaluated in terms of treatment results, 15 (60%) patients successfully completed the treatment. Conclusion: Our study is the first study in the literature that evaluated the drug hypersensitivity in drug resistance tuberculosis patients. Drug hypersensitivity that develops with tuberculosis treatment may lead to discontinuation or change in treatment. It can cause treatment failure, drug resistance, relapse, and even death. In resistant tuberculosis, the already existing resistance pattern may become more difficult to treat. Success can be achieved with the right management in these patients who have few treatment options, more drug side effects, and high treatment failure rates. The established regimen should be curative and prevent recurrence.