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Immunoglobulin A (IgA) nephropathy (IgAN) treatment consists of maximal supportive care and, for high-risk individuals, immunosuppressive treatment (IST). There are conflicting results regarding IST. Therefore, we aimed to investigate IST results among IgAN patients in Turkiye. The data of 1656 IgAN patients in the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases Study Group were analyzed. A total of 408 primary IgAN patients treated with IST (65.4% male, mean age 38.4 ± 12.5 years, follow-up 30 (3–218) months) were included and divided into two groups according to treatment protocols (isolated corticosteroid [CS] 70.6% and combined IST 29.4%). Treatment responses, associated factors were analyzed. Remission (66.7% partial, 33.7% complete) was achieved in 74.7% of patients. Baseline systolic blood pressure, mean arterial pressure, and proteinuria levels were lower in responsives. Remission was achieved at significantly higher rates in the CS group (78% vs. 66.7%, p = 0.016). Partial remission was the prominent remission type. The remission rate was significantly higher among patients with segmental sclerosis compared to those without (60.4% vs. 49%, p = 0.047). In the multivariate analysis, MEST-C S1 (HR 1.43, 95% CI 1.08–1.89, p = 0.013), MEST-C T1 (HR 0.68, 95% CI 0.51–0.91, p = 0.008) and combined IST (HR 0.66, 95% CI 0.49–0.91, p = 0.009) were found to be significant regarding remission. CS can significantly improve remission in high-risk Turkish IgAN patients, despite the reliance on non-quantitative endpoints for favorable renal outcomes. Key predictors of remission include baseline proteinuria and specific histological markers. It is crucial to carefully weigh the risks and benefits of immunosuppressive therapy for these patients. [ABSTRACT FROM AUTHOR]

The number of older adults undergoing organ transplantation, and waiting lists are increasing. The epidemiological data on infections in older transplant patients are scarce. The objective of the study was to investigate the incidence and distribution of infectious complications in older patients according to post-transplant periods. This retrospective study was conducted in a university hospital between 1 January 2018 and 31 March 2023. All infectious episodes were analyzed over three post-transplant periods. Forty-four patients were enrolled. The median age was 67 years (min: 65 and max: 87 years). Patients experienced a total of 98 infectious episodes. The median number of infectious events per patient was 1.0 (min: 0 and max: 8). The overall incidence rate of infectious events was 2.18 infectious episodes per 1000 transplant days. Of the patients at risk, 18.2% had 12 (12.4% of all infections) infections in the first month (9.09 episodes per 1000 transplant days), 56.8% had 52 (53.1%) infections between 1 and 6 months (7.88 episodes per 1000 transplant days), and 40.9% had 34 (35%) infections >6–12 months post-transplant (0.92 episodes per 1000 transplant days) The most prevalent type of infection was bacterial (79.6%, n = 78) followed by viral (18.4%, n = 18) and fungal (2.0%, n = 2) infections. The overall mortality rate of the 44 patients was 13.6%. The bacterial infections were more prevalent, and the incidence of infection was high during all post-transplant periods. These results may guide infection management in older transplant patients. [ABSTRACT FROM AUTHOR]

Purpose: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. Methods: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. Results: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. Conclusion: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance. [ABSTRACT FROM AUTHOR]

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not only posed major health and economic burdens to international societies but also threatens patients with comorbidities and underlying autoimmune disorders, including Crohn’s disease (CD) patients. As the vaccinated population is gradually relieved from the stress of the latest omicron variant of SARS-CoV-2 due to competent immune responses, the anxiety of CD patients, especially those on immunosuppressive treatment, has not subsided. Whether the use of immunosuppressants for remission of CD outweighs the potential risk of severe coronavirus disease 2019 (COVID-19) has long been discussed. Thus, for the best benefit of CD patients, our primary goal in this study was to navigate the clinical management of CD during the COVID pandemic. Herein, we summarized COVID-19 outcomes of CD patients treated with immunosuppressive agents from multiple cohort studies and also investigated possible mechanisms of how SARS-CoV-2 impacts the host immunity with special consideration of CD patients. We first looked into the SARS-CoV-2-related immunopathology, including lymphocytopenia, T-cell exhaustion, cytokine storms, and their possible molecular interactions, and then focused on mechanistic actions of gastrointestinal systems, including interruption of tryptophan absorption, development of dysbiosis, and consequent local and systemic inflammation. Given challenges in managing CD, we summarized up-to-date clinical and molecular evidence to help physicians adjust therapeutic strategies to achieve the best clinical outcomes for CD patients.

Abstract Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism.

The balance between apoptosis and autophagy plays a key role in cancer biology and treatment strategies. The aim of this study was to assess the effect of the mTOR kinase inhibitor everolimus and chloroquine on the regulation of proliferation, caspase-3 activation, and apoptosis in melanoma cells. We studied the activity of caspase-3 and the levels of caspase-3 and -9 using the Western blot technique. Cellular apoptosis was examined using a DNA fragmentation assay, and changes in the cell nucleus and cytoskeleton were examined using fluorescence microscopy DAPI, OA/IP. We also studied the rearrangement of lipid structures using fluorescent dyes: Nile Red and Nile Blue. A low nanomolar concentration of the mTOR kinase inhibitor everolimus in combination with chloroquine activated the apoptosis process and decreased cell proliferation. These changes were accompanied by an obvious change in cell morphology and rearrangement of lipid structures. Alterations in lipid redistribution accompanying the process of apoptosis and autophagy are among the first to occur in the cell and can be easily monitored in in vitro studies. The combination of mTOR inhibitors and chloroquine represents a promising area of research in cancer therapy. It has the potential to enhance treatment efficacy through complementary mechanisms. [ABSTRACT FROM AUTHOR]

The pathogenesis of immune thrombocytopenia (ITP) is complex and involves the dysregulation of immune cells, such as T and B lymphocytes, and several cytokines that promote the production of autoantibodies. In the context of cancer patients, ITP can occur in both primary and secondary forms related to anticancer therapies or the disease itself. Objective: In light of these data, we decided to prepare a literature review that will explain the classification and immunological determinants of the pathogenesis of ITP and present the clinical implications of this condition, especially in patients with cancer. Materials and methods: We reviewed the literature on immunological mechanisms, therapies, and challenges in treating ITP, particularly on cancer patients. Results: The results of the literature review show that ITP in cancer patients can be both primary and secondary, with secondary ITP being more often associated with anticancer therapies such as chemotherapy and immunotherapy. Innovative therapies such as TPO-RA, rituximab, Bruton's kinase inhibitors, and FcRn receptor inhibitors have shown promising results in treating refractory ITP, especially in patients with chronic disease. Conclusions: ITP is a significant clinical challenge, especially in the context of oncology patients, where both the disease and treatment can worsen thrombocytopenia and increase the risk of bleeding complications. Treatment of oncology patients with ITP requires an individualized approach, and new therapies offer effective tools for managing this condition. Future research into immunological mechanisms may bring further advances in treating ITP and improve outcomes in cancer patients. [ABSTRACT FROM AUTHOR]

Background: Seronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARSCoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger. Methods: We conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022. Results: Thirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients' clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before. Conclusion: In cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement. [ABSTRACT FROM AUTHOR]

Background: Individuals encountering hepatitis B virus (HBV) are at risk of hepatitis B virus reactivation (HBVr) when exposed to immunosuppressive (IS) therapy. Here, we aimed to evaluate neurologists' knowledge on HBVr in patients receiving IS treatment and draw attention to importance of the issue. Methods: Eighty-six physicians from neurology departments throughout Turkey between 1st March30th April 2020 were enrolled. Results: Of 86 physicians (average age 37.2±7.6 years), 34 (39.5%) were affiliated with university hospitals, 23 (26.7%) in training and research hospitals, and 29 (33.6%) in secondary healthcare centers. While 28 (32.5%) stated following a guideline, 58 (67.4%) declared following no guidelines. Physicians receiving postgraduate training on HBVr administered prophylaxis before IS treatment at a higher rate (p=0.04), and 69 (80.2%) considered all patients receiving any IS treatment should be screened for HBVr. To all participants, patients selected for screening should be tested for HBsAg; 83 (96.6%) and 29 (33.3%) stated patients should be tested for anti-HBs and anti-HBc IgG, respectively. Conclusion: Given our study findings, rate of screening performed by neurologists to give IS treatment for HBVr and their awareness level on the situation were not found to be sufficient. In addition, two more important factors required to be raised awareness were detected in our study: First, the rate of using anti-HBc in screening is low, and the awareness should be increased in this direction. Secondly, the risk of HBVr should be categorized in terms of IS treatment and host in our country where HBV infection is seen at a high rate, and determining the prophylactic approach is insufficient. [ABSTRACT FROM AUTHOR]

Patients on B cell immunosuppressive treatments have been shown to have persistent infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, a woman treated with ibrutinib for chronic lymphocytic leukemia experienced more than 40 days of coronavirus disease 2019 (COVID-19) infection. Unexpectedly, her peripheral blood experiments showed a normal SARS-CoV-2-specific antibody level and a relatively elevated percentage of CD19 + B cells, while an obvious decrease in the percentages of NK cells, CD4 + T cells and CD8 + T cells. Further SARS-CoV-2-specific T cell analysis in this patient indicated a significant decrease in the percentage of SARS-CoV-2-specific IFN-γ, TNF-α or IL-2 producing CD4 + T or CD8 + T cells. Most notably, ten days after the cease of ibrutinib, the PCR for SARS-CoV-2 turned negative and the reduced proportions of peripheral CD4 + T cells and CD8 + T cells recovered. Our research predicted that the depleted B-cell function therapies may play considerable role in the development of long COVID-19 and the abnormal T-cell subset distribution might be the underlying mechanism. [ABSTRACT FROM AUTHOR]

Copyright of Bosphorus Medical Journal / Boğaziçi Tıp Dergisi is the property of KARE Publishing and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acquired Aplastic Anemia (AAA) is a rare disease involving primary bone marrow failure with consequent pancytopenia. The addition of the synthetic thrombopoietin-receptor agonist eltrombopag (ELT) to standard immunosuppression for the treatment of AAA has led to improvements in hemopoietic outcomes of AAA. Most of the data on the use of ELT for AAA was based on a maximum of 6 months of therapy. However, in clinical practice, a longer use of ELT is often required. This paper presents a monocentric real-life experience with prolonged use of ELT in 10 patients with AAA, showing data on effectiveness and safety. In our cohort, a high rate of response to ELT added to standard immunosuppression in patients with varying grades of severity of AAA was reported. After a median (range) observation time of 47.5 (31–75) months, the treatment with ELT was feasible with an overall response probability of 70% and was not associated with any concerning adverse event. Two episodes of relapse were reported; no signs of evolution have been reported so far. In conclusion, ELT as a dose-response-adjusted prolonged therapy associated with standard immunosuppression in AAA patients not eligible for transplant seems to be feasible to consolidate and maintain the response.

Zhuajin Bi,1,2 Huajie Gao,1,2 Jing Lin,1,2 Mengcui Gui,1,2 Yue Li,1,2 Zhijun Li,1,2 Bitao Bu1,2 1Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 2Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Zhijun Li, Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China, Email lizhijun@tjh.tjmu.edu.cn Bitao Bu, Email bubitao@tjh.tjmu.edu.cnPurpose: To investigate the predictors for poor outcomes (including disease exacerbation, hospitalization and myasthenic crisis) in patients with pre-existing myasthenia gravis (MG) following Coronavirus disease 2019 (COVID-19), and to explore the potential effects of COVID-19 on inflammatory and immune responses in MG patients.Patients and Methods: This retrospective cohort study analyzed medical records of 845 MG patients who were diagnosed with COVID-19 between January 2020 to March 2023 at a single medical center.Results: Generalized MG at onset and comorbidities (chronic kidney disease and malignancy) were independent risk factors of poor outcomes. Patients achieving minimal manifestation or better status before COVID-19 had a significantly reduced risk for poor outcomes. Furthermore, patients with older onset age or anti-acetylcholine receptor antibody had a higher risk of exacerbation and hospitalization than those without. Prednisone or immunosuppressant treatment had the potential to reduce the occurrence of poor outcomes, while the duration of prednisone or immunosuppressant usage was associated with a higher risk of poor outcomes. Of the 376 MG patients with blood results available, patients with COVID-19 tended to have higher levels of leukocyte counts, neutrophil-lymphocyte-ratio, hypersensitive C-reactive protein, and Interleukin-6, as well as lower percentages of lymphocytes and regulatory T cells compared to patients without COVID-19.Conclusion: Disease severity at onset, comorbidities, and unsatisfactory control of myasthenic symptoms predicted the occurrence of poor outcomes in MG patients following COVID-19. The risk of poor outcomes was reduced in patients controlled by short-term immunosuppressive therapy. Novel coronavirus might affect inflammatory and immune responses in MG patients, particularly in altering interleukin-6 and regulatory T cell levels.Keywords: myasthenia gravis, COVID‐19, poor outcomes, immunosuppressive treatment, immune responses

A 54-year-old, one-eyed Caucasian male was admitted to the Ophthalmology Clinic due to a gradual deterioration of vision in the right eye for approximately two weeks. The patient denied any trauma or viral infection during this time. On the day of admission, the patient's best corrected visual acuity (BCVA) in the right eye was 0.5 on the Snellen scale. The patient's left eye had been atrophied for several years, with no light perception and no visibility of the fundus due to previous trauma and multiple surgeries. Ophthalmologic examination of the anterior segment and vitreous body of both eyes showed no signs of inflammation. Fundus examination of the right eye revealed scattered inflammatory foci, creamy-yellow and round, visible in all sectors. Laboratory tests, imaging studies, optical coherence tomography (OCT) angiographies, OCTs of the macula and optic nerve head, fluorescein angiographies (FAs), electroretinograms (ERGs), and visual field tests were performed. These examinations led to a diagnosis of a disease resembling birdshot-like chorioretinopathy. Immunogenetic testing of the patient did not reveal the presence of human leukocyte antigen (HLA)-A29. Dermatological and immunological consultations were conducted, and a differential diagnosis was made. Due to the reduced visual acuity (VA) observed and the inability to assess the left eye, a high-dose corticosteroid therapy was initiated, which was gradually tapered, along with the application of an immunosuppressive drug. The course of the disease was typical for birdshot chorioretinopathy, with chronic periods of remissions and exacerbations. The patient's clinical improvement was only achieved after co-administration of general corticosteroids at a dose of 0.5–1 mg/kg/day, mycofenolate mofetil, and periocular (sub-Tenon's) triamcinolone. [ABSTRACT FROM AUTHOR]

Obesity is frequent among organ transplant recipients, increasing the risk of acute graft rejection and overall morbimortality. Laparoscopic sleeve gastrectomy (LSG) effectively improves graft survival and associated comorbidities. We first compared 30-d outcomes between chronic immunosuppressed (CI) and nonchronic immunosuppressed (non-CI) patients. Then, between organ transplant and non-organ transplant CI patients who underwent LSG. Patients who underwent LSG within the metabolic and bariatric surgery accreditation and quality improvement program 2017-2019 were included. Using 1:1 and 1:4 propensity score matching analysis, the cohorts were matched for 30 characteristics. We then compared 30-d outcomes between CI and non-CI (analysis 1) and between organ transplant and non-organ transplant CI patients who underwent LSG (analysis 2). A total of 486,576 patients were included. The matched cohorts in analysis 1 (n = 8978) and analysis 2 (n = 1152, n = 371) had similar preoperative characteristics. Propensity score matching in analysis 1 showed that patients in the CI group had significantly higher rates of renal complications (0.4% versus 0.2%, P = 0.006), unplanned intensive care unit admission (1.1% versus 0.7%, P = 0.003), blood transfusions (1.1% versus 0.7%, P = 0.003), readmissions (4.6% versus 3.5%, P < 0.001), reoperations (1.4% versus 1.0%, P = 0.033), interventions (1.3% versus 1.0%, P = 0.026), and postoperative bleeding (0.6% versus 0.4%, P = 0.013). In analysis 2, patients with organ transplant CI had a higher rate of pulmonary complications (1.1% versus 0.3%, P = 0.043), renal complications (2.4% versus 0.2%, P < 0.001), blood transfusions (6.5% versus 1.3%, P < 0.001), and readmissions (10.0% versus 4.6%, P < 0.001). Patients with transplant-related CI who underwent LSG have higher 30-d postoperative complication rates compared to nontransplant-related CI patients; however, there were no differences in terms of mortality, intensive care unit admissions, staple line leaks, or bleeding. LSG is safe and feasible in this high-risk population. [ABSTRACT FROM AUTHOR]

Introduction: Hepatitis B virus (HBV) reactivation (HBVr) induced by chemotherapy in patients with resolved or chronic infection can lead to severe consequences. Despite recommendations, rates of HBV screening before chemotherapy are low due to poor recognition of risk factors by clinicians. The aim of the study is to assess whether routine HBV screening using universal HBV screening on chemotherapy orders (CO) could reduce HBVr incidence. Methods: This is a 1-year retrospective single-center observational study of patients who received intravenous chemotherapy post implementation of CO. We compared the incidence of HBVr in three groups of patients: those screened through CO (group 1), those screened by the medical team (group 2), and those not screened (group 3). Results: On a total of 1374 patients, 179 of 206 patients were screened as requested on CO (group 1) and 421 by the medical team (group 2), whereas 747 patients were not screened (group 3). Only one HBVr occurred, and no difference was seen on the incidence of HBVr between group 1 and group 3 (0% vs 0.1%; p = 1.00), probably because of a lack of follow-up after chemotherapy. Follow-up for HBVr was imperfect in group 1 and group 2 (16.7% vs 5.6%; p = 0.32). Screening was done for 92% of patients on anti-CD20 therapy. In group 3, 89 patients had ALT elevation during chemotherapy but only 17 (19%) were tested for HBVr. Conclusion: Systematic HBV detection requested on CO is an effective way to obtain a high percentage of patients with adequate screening, particularly when chemotherapy is at high risk of HBVr. Nevertheless, this screening method do not guarantee optimal follow-up and requires improvements. [ABSTRACT FROM AUTHOR]

BackgroundSeronegative autoimmune hepatitis in children is a rare but potentially severe disease, sometimes requiring liver transplantation. This type of hepatitis may be associated with various immunological and hematological disorders, ranging from isolated lymphopenia to aplastic anemia. Precise pathophysiological mechanisms are still unknown, but the role of viruses cannot be excluded, either as directly pathogenic or as triggers, responsible for an inappropriate immune stimulation. Having the impression of an increasing number of seronegative autoimmune hepatitis since the beginning of SARS-CoV-2 pandemia period, we hypothesized that SARS-CoV-2 virus could be an infectious trigger.MethodsWe conducted a retrospective, observational, descriptive study about children with seronegative autoimmune hepatitis, in a tertiary care center, between 2010 and 2022.ResultsThirty-two patients were included. The overall incidence of seronegative autoimmune hepatitis increased 3.3-fold in 2020-2022, during the SARS-CoV-2 pandemia period (16 patients in 2.8 years) compared with 2010-2019 the pre pandemia period (16 patients in 9 years). Patients’ clinical and biochemical liver characteristics did not differ between the two periods. Hematological damages were less severe during the pandemia period. Immunological studies revealed a dysregulated immune response. The initiation of immunosuppressive therapy (corticosteroids ± cyclosporine) was earlier during the pandemia period than before.ConclusionIn cases of undetermined acute hepatitis, an immune-mediated origin should be considered, prompting a liver biopsy. If the histological aspect points to an immune origin, immunosuppressive treatment should be instituted even though autoimmune hepatitis antibodies are negative. Close hematological monitoring must be performed in all cases. The 3.3-fold increase of cases during the SARS-CoV-2 pandemia will need to be further analyzed to better understand the underlying immunological mechanisms, and to prove its potential involvement.

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Grays test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p

The number of older adults undergoing organ transplantation, and waiting lists are increasing. The epidemiological data on infections in older transplant patients are scarce. The objective of the study was to investigate the incidence and distribution of infectious complications in older patients according to post-transplant periods. This retrospective study was conducted in a university hospital between 1 January 2018 and 31 March 2023. All infectious episodes were analyzed over three post-transplant periods. Forty-four patients were enrolled. The median age was 67 years (min: 65 and max: 87 years). Patients experienced a total of 98 infectious episodes. The median number of infectious events per patient was 1.0 (min: 0 and max: 8). The overall incidence rate of infectious events was 2.18 infectious episodes per 1000 transplant days. Of the patients at risk, 18.2% had 12 (12.4% of all infections) infections in the first month (9.09 episodes per 1000 transplant days), 56.8% had 52 (53.1%) infections between 1 and 6 months (7.88 episodes per 1000 transplant days), and 40.9% had 34 (35%) infections >6–12 months post-transplant (0.92 episodes per 1000 transplant days) The most prevalent type of infection was bacterial (79.6%, n = 78) followed by viral (18.4%, n = 18) and fungal (2.0%, n = 2) infections. The overall mortality rate of the 44 patients was 13.6%. The bacterial infections were more prevalent, and the incidence of infection was high during all post-transplant periods. These results may guide infection management in older transplant patients.

Objective: Non-adherence to immunosuppressive treatment can cause graft rejection in kidney transplantation patients. The reasons for nonadherence have been shown to be side-effects of the drugs, compliance fear, and lack of family support. The aim of this study was to determine the effect of family support on drug adherence. Material and Method: This study was conducted on 98 patients followed up in the polyclinic of a public hospital following kidney transplantation. The data were obtained from a patient information form, the Perception of Family Support Scale (PSS-Fa), the Immunosuppressive Treatment Adherence Scale (ITAS), and the tacrolimus blood plasma level of the patients. Results: In patients aged =40 years, the PSS-Fa was determined to be high (p <0.05), and family support was determined to have no effect on time since transplantation, donor type and rejection attack (p >0.05). The mean ITAS points were 11.03±0.90 and the tacrolimus blood plasma level mean standard deviation was <2.47, indicating high drug adherence. A positive correlation was determined between age and ITAS points (p <0.05). No correlation was determined between the tacrolimus blood plasma level standard deviation mean value and the ITAS and PSS-Fa mean points (p >0.05). Conclusion: No relationship was determined between family support and drug adherence. Further studies can be recommended to evaluate groups including different transplantation types to investigate the effect of family support on drug adherence. [ABSTRACT FROM AUTHOR]

Introduction: Pediatric heart transplant patients are routinely followed in dermatology clinics due to elevated risk of cutaneous malignancy. However, transplant patients may experience other, non‐cancer‐related dermatologic conditions including skin infections, inflammatory diseases, and drug eruptions that can cause significant medical and psychosocial comorbidity. Methods: A retrospective chart review of all pediatric heart transplant patients at Mayo Clinic Children's Center in Rochester, MN, was performed to determine the prevalence and spectrum of non‐cancer dermatologic conditions. Statistical analysis was conducted to look for associations between episodes of rejection and skin condition development. Results: Of the 65 patients who received heart transplants under the age of 18 and were followed at Mayo Clinic, 69% (N = 45) were diagnosed with at least one skin condition between transplant and the time of most recent follow‐up. Sixty‐two percent (N = 40) of patients were diagnosed with an inflammatory skin condition (most commonly acne and atopic dermatitis), 45% (N = 29) with an infectious skin condition (most commonly warts and dermatophyte infection), and 32% (N = 21) with a drug eruption (most commonly unspecified rash and urticaria). No association was found between presence of skin disease and number of rejection episodes. Conclusions: Non‐cancer dermatologic conditions are prevalent within pediatric heart transplant recipients and may directly impact their medical needs and quality of life. Dermatologist involvement in the care of post‐transplant pediatric patients is important, not only for cancer screening but also for diagnosis and treatment of common infectious and inflammatory skin conditions. [ABSTRACT FROM AUTHOR]

Cardiac involvement (CI) is rare in Behçet syndrome (BS), but the important point is that CI may be the first manifestation of the disease. The presence of CI worsens the prognosis of BS, so early diagnosis and early initiation of immunosuppressive treatment (IST) are vital. Coronary aneurysm may develop spontaneously in these patients, or any vascular intervention may cause aneurysm with a pathergy‐like reaction. The risk of restenosis is high after percutaneous coronary intervention or coronary artery bypass surgery applied without IST. Therefore, it should be kept in mind that IST constitutes the main step of treatment. Herein, we present a young male diagnosed with BS after acute coronary syndrome caused by coronary artery aneurysms and thrombosis. [ABSTRACT FROM AUTHOR]

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

Copyright of Biologie Aujourd'hui is the property of EDP Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acquired Aplastic Anemia (AAA) is a rare disease involving primary bone marrow failure with consequent pancytopenia. The addition of the synthetic thrombopoietin-receptor agonist eltrombopag (ELT) to standard immunosuppression for the treatment of AAA has led to improvements in hemopoietic outcomes of AAA. Most of the data on the use of ELT for AAA was based on a maximum of 6 months of therapy. However, in clinical practice, a longer use of ELT is often required. This paper presents a monocentric real-life experience with prolonged use of ELT in 10 patients with AAA, showing data on effectiveness and safety. In our cohort, a high rate of response to ELT added to standard immunosuppression in patients with varying grades of severity of AAA was reported. After a median (range) observation time of 47.5 (31–75) months, the treatment with ELT was feasible with an overall response probability of 70% and was not associated with any concerning adverse event. Two episodes of relapse were reported; no signs of evolution have been reported so far. In conclusion, ELT as a dose-response-adjusted prolonged therapy associated with standard immunosuppression in AAA patients not eligible for transplant seems to be feasible to consolidate and maintain the response. [ABSTRACT FROM AUTHOR]

Abstract Background There is no standard recommendation for IgA nephropathy treatment in children. Methods This is a retrospective study. From 2012 to 2020, newly diagnosed primary IgAN followed up for at least 1 year were enrolled. The correlation of MESTC scores and clinical index including proteinuria, gross hematuria and renal dysfunction was analyzed. Treatment and clinical response of 6 month, 1year and 3 year at follow up were also analyzed. Complete renal remission was calculated with Kaplan-Meier analysis. Results The median follow up was 36 months, from 12 months to 87months in 40 IgAN children. Angiotensin-converting enzyme inhibitor (ACEI) was applied to all patients. 30% received ACEI alone; 15% received glucocorticoids; 37.5% received glucocorticoids plus cyclophosphamide, 17.5% received glucocorticoids plus mycophenolate mofetil. Individuals with diffuse mesangial hypercellularity (M1) were more likely to have nephrotic range proteinuria compared to patients with M0 (80% vs. 20%, P

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Aplastic anemia (AA) is an uncommon condition characterized by pancytopenia and hypocellular bone marrow. Interleukin (IL)-6 and IL-8 have been shown to inhibit myelopoiesis and are major mediators of tissue damage. The primary goal of this study was to determine the IL-6 and IL-8 levels in children with AA, as well as their relationship to illness severity and immunosuppressive medication response. Materials and Methods: The IL-6 and IL-8 levels were tested in 50 children aged 3–18 years who had AA. As controls, 50 healthy age and sex matched individuals were used. A sandwich enzyme-linked immunosorbent assay kit (solid-phase) was used to measure IL-6 and IL-8 levels quantitatively. The concentrations of IL-6 and IL-8 in pg/mL were used to represent the results. Immunosuppressive medication was given to the patients in accordance with the British Committee for Standards in Haematology Guidelines 2009. Results: The patients' average age was 11.3 ± 3.7 years. Patients with AA had significantly higher IL-6 and IL-8 levels than controls (278.88 ± 216.03 vs. 4.51 ± 3.26; P < 0.001) and (120.28 ± 94.98 vs. 1.79 ± 0.78; P < 0.001), respectively. The IL-6 and IL-8 levels were also investigated with respect to AA severity, with statistically significant differences (P < 0.01) between different grading strata. Patients with very severe AA (VSAA) had the highest IL-6 levels (499.52 ± 66.19), followed by severe AA (SAA) (201.28 ± 157.77) and non-SAA (NSAA) (22.62 ± 14.63). For IL-8 levels, a similar trend (P < 0.01) was detected, with values of 209.81 ± 38.85, 92.12 ± 78.0, and 9.29 ± 10.68 for VSAA, SAA, and NSAA, respectively. After 6 months of immunosuppressive treatment (IST), mean levels of IL-6 and IL-8 in responders and nonresponders were again assessed. The mean IL-6 level in the responders' group (46.50 ± 45.41) was significantly lower, when compared to the nonresponders' group (145.76 ± 116.32) (P < 0.001). Similarly, the mean IL-8 level in the responder's group (33.57 ± 27.14) was significantly lower, compared to the nonresponder's group (97.49 ± 69.00) (P < 0.001). Conclusions: Children with AA had higher IL-6 and IL-8 levels than normal age- and sex-matched controls. Increased levels were linked to the severity of the condition, suggesting that IL may have a role in AA. IL levels can be monitored in AA patients during IST, which can assist in predicting response to IST. Résumé Contexte: L'anémie aplastique (AA) est une affection peu fréquente caractérisée par une pancytopénie et une moelle osseuse hypocellulaire. Il a été démontré que l'interleukine (IL)-6 et l'IL-8 inhibent la myélopoïèse et sont des médiateurs majeurs des lésions tissulaires. L'objectif principal de cette étude était de déterminer les niveaux d'IL-6 et d'IL-8 chez les enfants atteints d'AA, ainsi que leur relation avec la gravité de la maladie et la réponse aux médicaments immunosuppresseurs. Matériel et méthodes: Les niveaux d'IL-6 et d'IL-8 ont été testés chez 50 enfants âgés de 3 à 18 ans atteints d'AA. 50 témoins sains appariés par l'âge et le sexe ont été utilisés. Un kit de dosage immuno-enzymatique en sandwich (phase solide) a été utilisé pour mesurer quantitativement les niveaux d'IL-6 et d'IL-8. de manière quantitative. Les concentrations d'IL-6 et d'IL-8 en pg/mL ont été utilisées pour représenter les résultats. Des médicaments immunosuppresseurs ont été administrés aux patients conformément aux directives 2009 du British Committee for Standards in Haematology. Résultats: L'âge moyen des patients était de 11,3 ± 3,7 ans. Les patients atteints d'AA présentaient des taux d'IL-6 et d'IL-8 significativement plus élevés que les témoins (278,88 ± 216,03 contre 4,51 ± 3,26 ; P < 0,001) et (120,28 ± 94,98 contre 1,79 ± 0,78 ; P < 0,001), respectivement. Les taux d'IL-6 et d'IL-8 ont également été étudiés en fonction de la gravité de l'AA, avec des différences statistiquement significatives (P < 0,01) entre les différentes strates de classement. Les patients présentant une AA très sévère (VSAA) avaient les taux d'IL-6 les plus élevés (499,52 ± 66,19), suivis par les patients atteints d'AA sévère (SAA) (201,28 ± 157,77) et les patients non-SAA (NSAA) (22,62 ± 14,63). Pour les niveaux d'IL-8, une tendance similaire (P < 0,01) a été détectée, avec des valeurs de 209,81 ± 38,85, 92,12 ± 78,0, et 9,29 ± 10,68 pour les VSAA, SAA et NSAA, respectivement. Après 6 mois de traitement immunosuppresseur traitement immunosuppresseur (IST), les niveaux moyens d'IL-6 et d'IL-8 chez les répondeurs et les non-répondeurs ont été à nouveau évalués. Le taux moyen d'IL-6 dans le groupe des répondeurs (46,50 ± 45,41) était significativement plus faible, par rapport au groupe des non-répondeurs (145,76 ± 116,32) (P < 0,001). De même, le niveau moyen d'IL-8 dans le groupe des répondeurs (33,57 ± 27,14) était significativement plus faible que dans le groupe des non-répondeurs (97,49 ± 69,00) (P < 0,001). Conclusions: Les enfants atteints d'AA présentaient des niveaux d'IL-6 et d'IL-8 plus élevés que les témoins normaux appariés selon l'âge et le sexe. L'augmentation des taux était liée à la gravité de l'affection, suggérant que l'IL pourrait jouer un rôle dans l'AA. Les niveaux d'IL peuvent être surveillés chez les patients atteints d'AA pendant l'IST, ce qui peut aider à prédire la réponse à l'IST. Mots-clés: Anémie aplastique, traitement immunosuppresseur, interleukine-6, interleukine-8 [ABSTRACT FROM AUTHOR]

Lupus nephritis (LN) is the most frequent serious manifestation of patients with systemic lupus erythematosus (SLE). Up to 60% of SLE patients develop LN, which has a significant impact on their quality of life and prognosis. Recent advances have improved the diagnostic approach to LN, and new drugs that block specific pathways and kidney damage progression have been developed. Several randomized and well-powered clinical trials have confirmed the efficacy of these agents in terms of proteinuria remission and preservation of kidney function in the medium and long term, with an acceptable safety profile and good tolerance. The combination of different therapies allows for reduction of the dose and duration of corticosteroids and other potentially toxic therapies and leads to an increase in the number of patients achieving complete remission of the disease. This consensus document carried out by the Spanish Group for the Study of Glomerular Diseases (GLOSEN) provides practical and updated recommendations, based on the best available evidence and clinical expertise of participating nephrologists. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Uludag University Medical Faculty / Uludağ Üniversitesi Tıp Fakültesi Dergisi is the property of Journal of Uludag University Medical Faculty and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Many signaling pathways are involved in the mammalian target of rapamycin (mTOR), and this serine/threonine kinase regulates the most important cellular processes such as cell proliferation, autophagy, and apoptosis. The subject of this research was the effect of protein kinase inhibitors involved in the AKT, MEK, and mTOR kinase signaling pathways on the expression of pro-survival proteins, activity of caspase-3, proliferation, and induction of apoptosis in melanoma cells. The following inhibitors were used: protein kinase inhibitors such as AKT—MK-2206, MEK—AS-703026, mTOR—everolimus and Torkinib, as well as dual PI3K and mTOR inhibitor—BEZ-235 and Omipalisib, and mTOR1/2—OSI-027 inhibitor in single-mode and their combinations with MEK1/2 kinase inhibitor AS-703026. The obtained results confirm the synergistic effect of nanomolar concentrations of mTOR inhibitors, especially the dual PI3K and mTOR inhibitors (Omipalisib, BEZ-235) in combination with the MAP kinase inhibitor (AS-703026) in the activation of caspase 3, induction of apoptosis, and inhibition of proliferation in melanoma cell lines. Our previous and current studies confirm the importance of the mTOR signal transduction pathway in the neoplastic transformation process. Melanoma is a case of a very heterogeneous neoplasm, which causes great difficulties in treating this neoplasm in an advanced stage, and the standard approach to this topic does not bring the expected results. There is a need for research on the search for new therapeutic strategies aimed at particular groups of patients. Effect of three generations of mTOR kinase inhibitors on caspase-3 activity, apoptosis and proliferation in melanoma cell lines. [ABSTRACT FROM AUTHOR]

Abstract Background Nephrotic syndrome (NS) in children is widely believed to be associated with severe changes in the immune system. Based on lymphocyte subset analysis, we examined the pathogenesis of immune deficiencies in children with NS with varying steroid sensitivity. Methods Our study utilized flow cytometry to retrospectively analyze the ratios of lymphocyte subsets in 204 children with nephrotic syndrome and 19 healthy children. Results Compared with healthy children, the ratio of CD4 + /CD8 + in onset and remission was decreased in SRNS group (p

This network meta-analysis (NMA) aims to investigate the efficacy and safety of different pharmacological treatments for idiopathic membranous nephropathy (IMN). Thirty-four relevant studies were extracted from PubMed, Embase, Cochrane database, and MEDLINE. Treatment with tacrolimus (TAC), cyclophosphamide (CTX), mycophenolate mofetil, chlorambucil (CHL), cyclosporin A (CSA), steroids, rituximab (RTX), and conservative therapy were compared. Outcomes were measured using remission rate and incidence of side effects. Summary estimates were expressed as the odds ratio (OR) and 95% confidence intervals (CIs). The quality of findings was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation approach. In the direct meta-analysis for comparison of complete remission (CR) rate, the curative effect of RTX is inferior to CTX (OR 0.37; CI 0.18, 0.75). In the NMA of CR rate, the results showed that the curative effects of CTX, CHL, and TAC were significantly higher than those of the control group. The efficacy of RTX is not inferior to the CTX (OR 0.81; CI 0.32, 2.01), and the level of evidence was moderate; CSA was not as effective as RTX, and the difference was statistically significant with moderate evidence (OR 2.98, CI 1.00, 8.91). In summary, we recommend CTX and RTX as the first-line drug for IMN treatment.

Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome and whilst advances have been made in the pathophysiology, diagnostics and management of other podocytopathies, primary FSGS remains the most elusive. It has been assumed for a long time that a circulatory permeability factor exists that mediates podocyte injury, and the potential for autoantibody-mediated disease therefore raises the question as to whether patients may benefit from targeted B-cell therapy with rituximab. The prospective case series of seven patients by Roccatello et al. adds to the limited but growing evidence suggesting that B-cell depletion therapy can be safe and effective in the treatment of primary FSGS. In this editorial we explore the available evidence that suggests how and in whom rituximab may play a role in the management of primary FSGS, as well as the limitations and other potential future treatments. Further research and randomized controlled trials are needed to include larger numbers of patients, feature genetic screening and incorporate data on B-cell kinetics as a potential guide for dosing and frequency of rituximab. [ABSTRACT FROM AUTHOR]

Purpose: FOXP3 deficiency results in severe multisystem autoimmunity in both mice and humans, driven by the absence of functional regulatory T cells. Patients typically present with early and severe autoimmune polyendocrinopathy, dermatitis, and severe inflammation of the gut, leading to villous atrophy and ultimately malabsorption, wasting, and failure to thrive. In the absence of successful treatment, FOXP3-deficient patients usually die within the first 2 years of life. Hematopoietic stem cell transplantation provides a curative option but first requires adequate control over the inflammatory condition. Due to the rarity of the condition, no clinical trials have been conducted, with widely unstandardized therapeutic approaches. We sought to compare the efficacy of lead therapeutic candidates rapamycin, anti-CD4 antibody, and CTLA4-Ig in controlling the physiological and immunological manifestations of Foxp3 deficiency in mice. Method: We generated Foxp3-deficient mice and an appropriate clinical scoring system to enable direct comparison of lead therapeutic candidates rapamycin, nondepleting anti-CD4 antibody, and CTLA4-Ig. Results: We found distinct immunosuppressive profiles induced by each treatment, leading to unique protective combinations over distinct clinical manifestations. CTLA4-Ig provided superior breadth of protective outcomes, including highly efficient protection during the transplantation process. Conclusion: These results highlight the mechanistic diversity of pathogenic pathways initiated by regulatory T cell loss and suggest CTLA4-Ig as a potentially superior therapeutic option for FOXP3-deficient patients. [ABSTRACT FROM AUTHOR]

Background: There is no standard recommendation for IgA nephropathy treatment in children. Methods: This is a retrospective study. From 2012 to 2020, newly diagnosed primary IgAN followed up for at least 1 year were enrolled. The correlation of MESTC scores and clinical index including proteinuria, gross hematuria and renal dysfunction was analyzed. Treatment and clinical response of 6 month, 1year and 3 year at follow up were also analyzed. Complete renal remission was calculated with Kaplan-Meier analysis. Results: The median follow up was 36 months, from 12 months to 87months in 40 IgAN children. Angiotensin-converting enzyme inhibitor (ACEI) was applied to all patients. 30% received ACEI alone; 15% received glucocorticoids; 37.5% received glucocorticoids plus cyclophosphamide, 17.5% received glucocorticoids plus mycophenolate mofetil. Individuals with diffuse mesangial hypercellularity (M1) were more likely to have nephrotic range proteinuria compared to patients with M0 (80% vs. 20%, P < 0.01). Complete renal remission at 6-month, 1-year and 3-year follow up is 50.25%, 70% and 87.5% respectively. Five-year complete renal remission calculated by Kaplan-Meier analysis is 58.4%. Although without significant difference, there is trend of better survival with complete renal remission in group of nephrotic range proteinuria onset. There is no severe adverse effect. Conclusion: This study supports the use of glucocorticoids plus immunosuppressive in addition to ACEI in IgA nephrology pediatric patients with proteinuria. We suggest proactive immunosuppressive treatment in IgA nephropathy in children. This is from a single center in China as may not same results in other population. [ABSTRACT FROM AUTHOR]

Myasthenia gravis (MG) is characterized by muscle weakness caused by autoantibodies that bind to the postsynaptic membrane at the neuromuscular junction and impair acetylcholine receptor function. Weakness of respiratory muscles represents the most severe MG manifestation, and 10–15% of all patients experience an MG crisis with the need of mechanical ventilatory support at least once in their life. MG patients with respiratory muscle weakness need active immunosuppressive drug treatment long term, and they need regular specialist follow-up. Comorbidities affecting respiratory function need attention and optimal treatment. Respiratory tract infections can lead to MG exacerbations and precipitate an MG crisis. Intravenous immunoglobulin and plasma exchange are the core treatments for severe MG exacerbations. High-dose corticosteroids, complement inhibitors, and FcRn blockers represent fast-acting treatments that are effective in most MG patients. Neonatal myasthenia is a transient condition with muscle weakness in the newborn caused by mother's muscle antibodies. In rare cases, treatment of respiratory muscle weakness in the baby is required. [ABSTRACT FROM AUTHOR]

The occurrence of secondary neoplasms in adult patients treated with chemotherapy in childhood is not uncommon. Prior chemotherapy is found to be an independent risk factor for the development of secondary malignancies, which are usually associated with a worse prognosis. The presented case is a 35-year-old female patient who was diagnosed with Ewing sarcoma in her late adolescence. The tumor was successfully treated with chemotherapy, but 3 years later she was diagnosed with T-cell lymphoblastic lymphoma. The patient received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leukocyte antigen (HLA) matched related donor. The procedure was complicated by grade 2 acute graft-versus-host disease (GvHD) which resolved after implementation of immunosuppressive treatment. However, a year later, the patient developed extensive chronic GvHD (cGvHD) and required reintroduction of immunosuppressants. Prolonged immunosuppressive treatment with tacrolimus led to irreversible kidney failure. After a 2-year period of regular peritoneal dialysis, she was found to be eligible for a kidney transplant from a deceased donor. Now, 15 years after stem cell transplantation and 8 years after kidney transplantation, the patient remains in good condition overall, presenting with symptoms of limited cGvHD. The case described here presents a unique clinical scenario of a female patient who was successfully treated for her double malignancy. Moreover, she underwent effective double transplantations and was eventually found to be cured despite accompanying complications. [ABSTRACT FROM AUTHOR]

Renal transplantation is now the best treatment for end-stage renal failure. To avoid rejection and prolong graft function, organ recipients need immunosuppressive therapy. The immunosuppressive drugs used depends on many factors, including time since transplantation (induction or maintenance), aetiology of the disease, and/or condition of the graft. Immunosuppressive treatment needs to be personalised, and hospitals and clinics have differing protocols and preparations depending on experience. Renal transplant recipient maintenance treatment is mostly based on triple-drug therapy containing calcineurin inhibitors, corticosteroids, and antiproliferative drugs. In addition to the desired effect, the use of immunosuppressive drugs carries risks of certain side effects. Therefore, new immunosuppressive drugs and immunosuppressive protocols are being sought that exert fewer side effects, which could maximise efficacy and reduce toxicity and, in this way, reduce both morbidity and mortality, as well as increase opportunities to modify individual immunosuppression for renal recipients of all ages. The aim of the current review is to describe the classes of immunosuppressive drugs and their mode of action, which are divided by induction and maintenance treatment. An additional aspect of the current review is a description of immune system activity modulation by the drugs used in renal transplant recipients. Complications associated with the use of immunosuppressive drugs and other immunosuppressive treatment options used in kidney transplant recipients have also been described. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to compare the effects of cyclosporine (CsA) and tacrolimus (TAC) on preventing acute rejection and analyze the side-effect profiles of both agents, particularly on kidney functions. PATIENTS AND METHODS: In our study, 71 patients who underwent heart transplantation were included. For maintenance immunosuppression, 28 of these patients were treated with mycophenolate mofetil (MMF), steroid, and steroid CsA, and 43 of them were treated with MMF steroid and TAC. Endomyocardial biopsy results of the patients in the first month and the first year were compared. In the follow-ups, creatinine values and other parameters were recorded. RESULTS: Endomyocardial biopsy (EMB) performed at 1 month showed no rejection in 12 patients (42.9%) in the CsA group, grade 1R rejection in 15 patients (53.6%), and grade 2R rejection in one patient (3.6%). In the TAC group, rejection was not detected in 25 patients (58.1%), while grade 1R rejection was diagnosed in 17 patients (39.5%) and grade 2R rejection in 1 patient (2.3%) (p=0.4). In EMBs performed in the first year, 14 patients (51.9%) in the CsA group did not have rejection, 12 patients (44.4%) had grade 1R rejection, and one patient (3.7%) had grade 2R rejection. In the TAC group, grade 0R rejection was diagnosed in 23 patients (60.5%), grade 1R rejection in 15 patients (39.5%), and grade 2R rejection was not detected. Postoperative firstweek creatinine values, which were found to be higher in the CsA group, were significant compared to the TAC group (p=0.028). CONCLUSIONS: TAC and CsA are drugs that help prevent acute rejection after heart transplantation and can be used safely in heart transplant recipients. Neither drug is superior to the other in preventing rejection. TAC may be preferred to CsA as it has fewer negative effects on kidney functions in the early postoperative period. [ABSTRACT FROM AUTHOR]

Introduction: We examined the neutralizing antibody production efficiency of the second and third severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) vaccine doses (2nd- and 3rd-dose) and neutralizing activity on mutant strains, including, the Ancestral, Beta and Omicron strains using green fluorescent protein-carrying recombinant SARS-CoV-2, in living-donor liver transplantation (LDLT) recipients. Methods: The patients who were administered vaccines other than Pfizer-BioNTechBNT162b2 and who had coronavirus disease 2019 in this study period were excluded. We enrolled 154 LDLT recipients and 50 healthy controls. Result: The median time were 21 days (between 1st and 2nd vaccination) and 244 days (between 2nd and 3rd vaccination). The median neutralizing antibody titer after 2nd-dose was lower in LDLT recipients than in controls (0.46 vs 1.00, P<0.0001). All controls had SARS-CoV-2 neutralizing antibodies, whereas 39 LDLT recipients (25.3%) had no neutralizing antibodies after 2nd-dose; age at vaccination, presence of ascites, multiple immunosuppressive treatments, and mycophenolate mofetil treatment were significant risk factors for nonresponder. The neutralizing activities of recipient sera were approximately 3-fold and 5-fold lower than those of control sera against the Ancestral and Beta strains, respectively. The median antibody titer after 3rd-dose was not significantly different between recipients and controls (1.02 vs 1.22, p=0.0758); only 5% recipients was non-responder. The neutralizing activity after third dose to Omicron strains were enhanced and had no significant difference between two groups. Conclusion: Only the 2nd-dose was not sufficiently effective in recipients; however, 3rd-dose had sufficient neutralizing activity against the mutant strain and was as effective as that in healthy controls. [ABSTRACT FROM AUTHOR]

Enteritis associated with systemic lupus erythematosus (SLE) is a rare and unusual manifestation of the gastrointestinal (GI) consequences of SLE itself. Complications of the enteritis component include mesenteric vasculitis, intestinal pseudo-obstruction, and protein-losing enteropathy. Lupus enteritis is very responsive to treatment with pulse steroids in almost 70% of the patients, but it is critical to diagnose it early to prevent devastating organ damage. The case describes a 21-year-old Caucasian female with a past medical history of uncomplicated laparoscopic appendectomy (one month prior to the time of presentation), major depressive disorder, asthma, iron deficiency anemia, pelvic inflammatory disease secondary to sexually transmitted Chlamydia trachomatis infection, and SLE (diagnosed two weeks prior to presentation). She had been transferred from an outside facility with complaints of severe right upper quadrant (RUQ) abdominal pain for one day. The patient had run out of her prescription for steroids and hydroxychloroquine two days prior to the presentation. Her abdominal pain was accompanied by nausea, bilious vomiting, non-bloody diarrhea, a photosensitive facial rash, left-sided pressure-type periorbital headache, diplopia, oral ulcers, inappetence, joint stiffness, and muscle weakness. A CT of the abdomen and pelvis from an outside facility showed enteritis involving the proximal jejunum with associated mesenteric edema and ascites, suggesting infectious versus inflammatory or autoimmune etiology. A repeat CT scan a few days later confirmed these findings along with adjacent mesenteric fat stranding. Her autoimmune workup confirmed the serological diagnosis of SLE, and assessment of the SLE Disease Activity Index (SLEDAI) confirmed the diagnosis of a severe SLE flare. Upper endoscopy detected edematous mucosa in the duodenum and jejunum without active bleeding, gastropathy, or ulceration. No surgical intervention was required. Her symptoms resolved with supportive care, pulse steroids, and hydroxychloroquine. She was discharged with instructions for outpatient follow-up with gastroenterology and rheumatology.

Background: Despite the common use of mycophenolate in pediatric renal transplantation, lack of effective therapeuic drug monitoring increases uncertainty over optimal drug exposure and risk for adverse reactions. This study aims to develop a novel urine test to estimate MPA exposure based using metabolomics. Methods: Urine samples obtained on the same day of MPA pharmacokinetic testing from two prospective cohorts of pediatric kidney transplant recipients were assayed for 133 unique metabolites by mass spectrometry. Partial least squares (PLS) discriminate analysis was used to develop a top 10 urinary metabolite classifier that estimates MPA exposure. An independent cohort was used to test pharmacodynamic validity for allograft inflammation (urinary CXCL10 levels) and eGFR ratio (12mo/1mo eGFR) at 1 year. Results: Fifty‐two urine samples from separate children (36.5% female, 12.0 ± 5.3 years at transplant) were evaluated at 1.6 ± 2.5 years post‐transplant. Using all detected metabolites (n = 90), the classifier exhibited strong association with MPA AUC by principal component regression (r = 0.56, p <.001) and PLS (r = 0.75, p <.001). A practical classifier (top 10 metabolites; r = 0.64, p <.001) retained similar accuracy after cross‐validation (LOOCV; r = 0.52, p <.001). When applied to an independent cohort (n = 97 patients, 1053 samples), estimated mean MPA exposure over Year 1 was inversely associated with mean urinary CXCL10:Cr (r = −0.28, 95% CI −0.45, −0.08) and exhibited a trend for association with eGFR ratio (r = 0.35, p =.07), over the same time period. Conclusions: This urinary metabolite classifier can estimate MPA exposure and correlates with allograft inflammation. Future studies with larger samples are required to validate and evaluate its clinical application. [ABSTRACT FROM AUTHOR]