Delayed Onset of Thrombotic Microangiopathy (TMA) upon Prolonged Carfilzomib Therapy in Multiple Myeloma: A Case Report and Comprehensive Review.

Background: Thrombotic microangiopathy (TMA) is a potentially life-threatening complication associated with carfilzomib, a proteasome inhibitor approved for treating multiple myeloma. TMA typically presents within the initial months of treatment; however, delayed onset is rare and poses significant diagnostic challenges.

Methods: We conducted a retrospective analysis of the medical records of a 47-year-old Caucasian woman diagnosed with IgA kappa myeloma who developed signs and symptoms consistent with TMA eleven months after the initiation of carfilzomib therapy and already in ongoing very good partial remission.

Pregnancy in Complement-Mediated Thrombotic Microangiopathy: Maternal and Neonatal Outcomes.

Rationale & Objective: Pregnancy, delivery, and neonatal outcomes in women with complement-mediated thrombotic microangiopathy (cTMA) have not been well described. A better understanding of these outcomes is necessary to provide women with competent pregnancy counseling.

Study Design: Cohort study.

Complement lectin pathway activation is associated with COVID-19 disease severity, independent of genotype subgroups.

Introduction: While complement is a contributor to disease severity in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, all three complement pathways might be activated by the virus. Lectin pathway activation occurs through different pattern recognition molecules, including mannan binding lectin (MBL), a protein shown to interact with SARS-CoV-2 proteins. However, the exact role of lectin pathway activation and its key pattern recognition molecule MBL in COVID-19 is still not fully understood.

Hemolytic uremic syndrome in the setting of COVID-19 successfully treated with complement inhibition therapy: An instructive case report of a previously healthy toddler and review of literature.

Introduction: As the global pandemic continues, new complications of COVID-19 in pediatric population have turned up, one of them being hemolytic uremic syndrome (HUS), a complement-mediated thrombotic microangiopathy (CM-TMA) characterized by triad of thrombocytopenia, microangiopathic hemolytic anemia and acute kidney injury (AKI). With both multisystem inflammatory syndrome in children (MIS-C) and HUS sharing complement dysregulation as one of the key factors, the aim of this case report is to highlight differences between these two conditions and also emphasize the importance of complement blockade as a treatment modality.

Case Report: We describe a 21-month-old toddler who initially presented with fever and confirmed COVID-19.

Atypical hemolytic uremic syndrome triggered by mRNA vaccination against SARS-CoV-2: Case report.

Atypical hemolytic uremic syndrome (aHUS), also called complement-mediated hemolytic uremic syndrome (CM-HUS), is a rare disease caused by dysregulation in the alternative complement activation pathway. It is a life-threatening condition causing ischemia of a number of organs, and it typically causes acute kidney injury. This disorder may be triggered by various factors including viral or bacterial infections, pregnancy, surgery, and injuries.

haplotype is associated with poor graft survival in kidney transplant recipients with thrombotic microangiopathy.

thrombotic microangiopathy (TMA) is associated with poor kidney graft survival, and as we previously described, it is a recipient driven process with suspected genetic background. Direct Sanger sequencing was performed in 90 KTR with TMA and 90 corresponding donors on selected regions in , and genes that involve variations with a functional effect or confer a risk for aHUS. Additionally, 37 recipients of paired kidneys who did not develop TMA were analyzed for the haplotype.

Searching for Genetic Biomarkers for Hereditary Angioedema Due to C1-Inhibitor Deficiency (C1-INH-HAE).

Existing evidence indicates that modifier genes could change the phenotypic outcome of the causal variant and thus explain the expression variability of hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE). To further examine this hypothesis, we investigated the presence or absence of 18 functional variants of genes encoding proteins involved in the metabolism and function of bradykinin, the main mediator of C1-INH-HAE attacks, in relation to three distinct phenotypic traits of patients with C1-INH-HAE, i.e.

Diagnosing Pediatric Patients With Hereditary C1-Inhibitor Deficiency-Experience From the Hungarian Angioedema Center of Reference and Excellence.

Background: Hereditary Angioedema with C1-inhibitor deficiency (C1-INH-HAE) is a rare disease characterized by recurrent subcutaneous and/or submucosal edematous (HAE) episodes, which may occur at any age. The mean age of the symptom onset is 10-12 years. Diagnostic protocols differ by age group and family history.

Overview of SERPING1 Variations Identified in Hungarian Patients With Hereditary Angioedema.

Background: Hereditary angioedema (HAE) due to C1-inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare autosomal dominant disorder, characterized by recurrent, unpredictable edematous symptoms involving subcutaneous, and/or submucosal tissue. C1-INH-HAE may be caused by more than 700 different mutations in the gene encoding C1-INH () that may lead to decreased protein synthesis or to functional deficiency.

Methods: Concentrations of C1-INH, C4, C1q, and anti-C1-INH antibodies, as well as functional C1-INH activity were determined in subjects suffering from edematous symptoms and admitted to the Hungarian Angioedema Center of Reference and Excellence.

Complement Genetics for the Practicing Allergist Immunologist: Focus on Complement Deficiencies.

Complement deficiencies have been considered to be rare for many decades, but this assumption is changing year by year. Recognition of these conditions significantly increases thanks to the availability of different testing approaches and due to clinical awareness. Furthermore, sequencing technologies (including Sanger sequencing, targeted gene panels, and whole exome/genome sequencing) may facilitate the identification of the underlying disease-causing genetic background.

Variant Transthyretin Amyloidosis (ATTRv) in Hungary: First Data on Epidemiology and Clinical Features.

Background: Variant transthyretin amyloidosis (ATTRv) is an autosomal dominant inherited disease, where the mutation of the transthyretin gene (TTR) results in the deposition of pathogenic protein fibrils in various tissues. The mutation type influences the clinical course. Until now, no data were available on the genotype, phenotype, and prevalence of Hungarian ATTRv patients.

Reduction in hypoxia-reoxygenation-induced myocardial mitochondrial damage with exogenous methane.

Albeit previous experiments suggest potential anti-inflammatory effect of exogenous methane (CH ) in various organs, the mechanism of its bioactivity is not entirely understood. We aimed to investigate the potential mitochondrial effects and the underlying mechanisms of CH in rat cardiomyocytes and mitochondria under simulated ischaemia/reperfusion (sI/R) conditions. Three-day-old cultured cardiomyocytes were treated with 2.

Complement Genetic Variants and FH Desialylation in -Haemolytic Uraemic Syndrome.

Haemolytic Uraemic Syndrome associated with infections (SP-HUS) is a clinically well-known entity that generally affects infants, and could have a worse prognosis than HUS associated to infections. It has been assumed that complement genetic variants associated with primary atypical HUS cases (aHUS) do not contribute to SP-HUS, which is solely attributed to the action of the pneumococcal neuraminidase on the host cellular surfaces. We previously identified complement pathogenic variants and risk polymorphisms in a few Hungarian SP-HUS patients, and have now extended these studies to a cohort of 13 Spanish SP-HUS patients.

The Role of Mannose-binding Lectin in Infectious Complications of Pediatric Hemato-Oncologic Diseases.

The complement system is essential for protection against infections in oncologic patients because of the chemotherapy-induced immunosuppression. One of the key elements in the activation of the complement system via the lectin pathway is the appropriate functioning of mannose-binding lectin (MBL) and mannose-binding lectin-associated serine protease 2 (MASP2) complex. The objective of our study was to find an association between polymorphisms resulting in low MBL level and activation of the MBL-MASP2 complex.

Methane supplementation improves graft function in experimental heart transplantation.

Background: Maintenance of cell viability during cold storage is a key issue in organ transplantation. Methane (CH) bioactivity has recently been recognized in ischemia/reperfusion conditions; we therefore hypothesized that cold storage in CH-enriched preservation solution can provide an increased defense against organ dysfunction during experimental heart transplantation (HTX).

Methods: The hearts of donor Lewis rats were stored for 60 minutes in cold histidine-tryptophan-ketoglutarate (Custodiol [CS]) or CH-saturated CS solution (CS-CH) (n = 12 each).

Validation of distinct pathogenic patterns in a cohort of membranoproliferative glomerulonephritis patients by cluster analysis.

Background: A novel data-driven cluster analysis identified distinct pathogenic patterns in C3-glomerulopathies and immune complex-mediated membranoproliferative glomerulonephritis. Our aim was to replicate these observations in an independent cohort and elucidate disease pathophysiology with detailed analysis of functional complement markers.

Methods: A total of 92 patients with clinical, histological, complement and genetic data were involved in the study, and hierarchical cluster analysis was done by Ward method, where four clusters were generated.

C4 nephritic factor in patients with immune-complex-mediated membranoproliferative glomerulonephritis and C3-glomerulopathy.

Background: Acquired or genetic abnormalities of the complement alternative pathway are the primary cause of C3glomerulopathy(C3G) but may occur in immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN) as well. Less is known about the presence and role of C4nephritic factor(C4NeF) which may stabilize the classical pathway C3-convertase. Our aim was to examine the presence of C4NeF and its connection with clinical features and with other pathogenic factors.

International Consensus on the Use of Genetics in the Management of Hereditary Angioedema.

Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories, and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex.

The effects of TNF-alpha inhibitor therapy on the incidence of infection in JIA children: a meta-analysis.

Background: Juvenile Idiopathic arthritis (JIA) is the most common chronic rheumatic disease in childhood. The diagnosis is based on the underlying symptoms of arthritis with an exclusion of other diseases Biologic agents are increasingly used on the side of disease-modifying anti-rheumatic drugs (DMARD) in JIA treatment.

Main Body: The aim of this meta-analysis was to investigate the observed infections in JIA children during tumor necrosis factor (TNF)-alpha inhibitor therapy.

Theory of mind disturbances in borderline personality disorder: A meta-analysis.

Impairments of theory of mind (ToM) are widely accepted underlying factors of disturbed relatedness in borderline personality disorder (BPD). The aim of this meta-analysis a was to assess the weighted mean effect sizes of ToM performances in BPD compared to healthy controls (HC), and to investigate the effect of demographic variables and comorbidities on the variability of effect sizes across the studies. Seventeen studies involving 585 BPD patients and 501 HC were selected after literature search.

Concentration and Subclass Distribution of Anti-ADAMTS13 IgG Autoantibodies in Different Stages of Acquired Idiopathic Thrombotic Thrombocytopenic Purpura.

Background: The acquired form of idiopathic thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease, in which the underlying deficiency of the ADAMTS13 protease is caused by autoantibodies, predominantly of the IgG isotype. Certain HLA-DR-DQ haplotypes were associated with the risk of developing TTP.

Objectives: To investigate the development of the ADAMTS13-specific antibody response during the course of the disease, we analyzed the concentration, subclass distribution, and inhibitory potential of anti-ADAMTS13 IgG autoantibodies in samples of TTP patients drawn during the first acute phase, in remission, and during relapse.

Electroporation-enhanced transdermal diclofenac sodium delivery into the knee joint in a rat model of acute arthritis.

Purpose: Since electroporation (EP) can increase the permeability of biological membranes, we hypothesized that it offers an opportunity to enhance the transdermal delivery of drugs for intra-articular indications. Our aim was to compare the anti-inflammatory and analgesic efficacy of EP-combined topical administration of diclofenac sodium hydrogel (50 mg mL in 230 µL volume) with that of an equivalent dose of oral (75 mg kg) and simple topical administration.

Methods: Arthritis was induced with the injection of 2% λ-carrageenan and 4% kaolin into the right knee joints of male Sprague Dawley rats.

Compared efficacy of preservation solutions on the outcome of liver transplantation: Meta-analysis.

Aim: To compare the effects of the four most commonly used preservation solutions on the outcome of liver transplantations.

Methods: A systematic literature search was performed using MEDLINE, Scopus, EMBASE and the Cochrane Library databases up to January 31, 2017. The inclusion criteria were comparative, randomized controlled trials (RCTs) for deceased donor liver (DDL) allografts with adult and pediatric donors using the gold standard University of Wisconsin (UW) solution or histidine-tryptophan-ketoglutarate (HTK), Celsior (CS) and Institut Georges Lopez (IGL-1) solutions.