Publications by authors named "Szamosi J"

Article Synopsis
  • Paroxysmal nocturnal haemoglobinuria (PNH) is a rare blood disorder causing serious issues due to chronic hemolysis and can significantly affect patients' quality of life.
  • A post hoc analysis evaluated the effectiveness of pegcetacoplan, a targeted complement C3 inhibitor, in PNH patients with poor bone marrow function from the PEGASUS and PRINCE studies.
  • Results showed that while normalisation of certain health parameters was challenging, a significant percentage of patients experienced clinically meaningful improvements in hemoglobin, LDH levels, and fatigue after treatment with pegcetacoplan.
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Introduction: Pegcetacoplan, the first approved proximal complement C3 inhibitor, showed superiority to eculizumab in improving hemoglobin levels and clinical outcomes in the phase 3 PEGASUS study in patients with paroxysmal nocturnal hemoglobinuria (PNH) and inadequate response to eculizumab.

Methods: This analysis evaluates the efficacy and safety of pegcetacoplan for Japanese patients in PEGASUS, as they are known for different clinicopathologic features compared to non-Asian patients. Ten Japanese patients were enrolled to receive pegcetacoplan (n=5) or eculizumab (n=5) during the 16-week randomized controlled period.

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Background: Prophylactic factor replacement therapy is recommended over on-demand treatment for preserving long-term joint health in hemophilia. Extended half-life products, including efmoroctocog alfa/eftrenonacog alfa (recombinant factor VIII [FVIII]/FIX Fc fusion proteins; herein rFVIIIFc/rFIXFc), have the potential to reduce treatment burden with less frequent administration and improve bleed prevention.

Objectives: We report post hoc data from patients with hemophilia A or B (HA/HB) who switched from prestudy on-demand FVIII/FIX to rFVIIIFc/rFIXFc prophylaxis at the start of A-LONG/B-LONG or start of/during ASPIRE/B-YOND phase 3 studies.

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Bacterial viruses, or bacteriophages, are highly potent, target-specific antimicrobials. Bacteriophages can be safely applied along the food production chain to aid control of foodborne pathogens. However, bacteriophages are often sensitive to the environments encountered in food matrices and under processing conditions, thus limiting their applicability.

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Background & Aims: Genes and gluten are necessary but insufficient to cause celiac disease (CeD). Altered gut microbiota has been implicated as an additional risk factor. Variability in sampling site may confound interpretation and mechanistic insight, as CeD primarily affects the small intestine.

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Background/purpose: Type 2 diabetes and obesity increase the risk of developing colorectal cancer. Metformin may reduce colorectal cancer but the mechanisms mediating this effect remain unclear. In mice and humans, a high-fat diet (HFD), obesity and metformin are known to alter the gut microbiome but whether this is important for influencing tumor growth is not known.

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Inflammatory bowel diseases (IBD) are chronic inflammatory conditions of the gastrointestinal tract. IBD are associated with a high prevalence of cognitive, behavioural and emotional comorbidities, including anxiety and depression. The link between IBD and the development of behavioural comorbidities is poorly understood.

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In rodents, lower brown adipose tissue (BAT) activity is associated with greater liver steatosis and changes in the gut microbiome. However, little is known about these relationships in humans. In adults (n = 60), we assessed hepatic fat and cold-stimulated BAT activity using magnetic resonance imaging and the gut microbiota with 16S sequencing.

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Objectives: Available information exists supporting the gut-brain axis, but additional information is needed to explore how the gut microbiome changes when exposed to mood disorder treatments. We sought to explore the effects of a novel treatment for bipolar disorder (BD), infliximab, on the gut microbiome.

Methods: Participants with a primary diagnosis of BD (n = 15) who participated in a 12-week, randomized placebo-controlled trial evaluating the efficacy of adjunctive infliximab in the treatment of BD were recruited and followed.

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Background: Since the EU approval of nitisinone in 2005, prognosis for patients with hereditary tyrosinaemia type 1 has changed dramatically, with patients living with the disease now reaching adulthood for the first time in history. This study aimed to assess the long-term safety and outcomes of nitisinone treatment in patients with hereditary tyrosinaemia type 1.

Methods: We did a non-interventional, non-comparative, multicentre study in 77 sites across 17 countries in Europe and collected retrospective and prospective longitudinal data in patients with hereditary tyrosinaemia type 1 who were treated with oral nitisinone during the study period (Feb 21, 2005, to Sept 30, 2019).

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Article Synopsis
  • - Early adverse care can lead to lasting effects on both physical and mental health, particularly by influencing the gut microbiome, which is crucial for growth and metabolism.
  • - A study compared the gut microbiota of adolescents adopted from orphanages to those raised in similar socio-economic families, revealing significant differences linked to early rearing conditions.
  • - Results indicated a relationship between specific gut bacteria, immune system profiles, and cytomegalovirus positivity, highlighting how early life challenges may affect immune health through the gut microbiota.
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Background: In studies evaluating the microbiome, numerous factors can contribute to technical variability. These factors include DNA extraction methodology, sequencing protocols, and data analysis strategies. We sought to evaluate the impact these factors have on the results obtained when the sequence data are independently generated and analyzed by different laboratories.

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Background: Alkaptonuria is a rare, genetic, multisystem disease characterised by the accumulation of homogentisic acid (HGA). No HGA-lowering therapy has been approved to date. The aim of SONIA 2 was to investigate the efficacy and safety of once-daily nitisinone for reducing HGA excretion in patients with alkaptonuria and to evaluate whether nitisinone has a clinical benefit.

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Introduction: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn's Disease (CD). CS are also therapy for ulcerative colitis (UC). Host-microbe interactions may be able to explain the effectiveness of these treatments.

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Background: Intestinal epithelial integrity is influenced by short-chain fatty acids (SCFAs) and is of critical importance for children with intestinal failure (IF) given the known devastating infectious and gastrointestinal complications. The composition of the microbiome in IF represents an important variable in the physiology and prognosis of this disease.

Aim: We sought to compare the intestinal microbiome and SCFA concentration of children who require parenteral nutrition (PN) with that of children with short-bowel syndrome (SBS) who have discontinued PN and with age-matched controls, using high-throughput sequencing to investigate host-microbe interactions.

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Introduction: Haemophilia A is a rare bleeding disorder caused by coagulation factor VIII (FVIII) deficiency. This is treated with factor VIII, conventionally using products with a half-life of 8-12 hours typically administered every 2-3 days. Recombinant FVIII Fc (rFVIIIFc) represents a new generation of products with an extended half-life allowing higher FVIII levels and longer dosing interval.

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Article Synopsis
  • In the phase 3 B-LONG study, the use of recombinant factor IX Fc fusion protein (rFIXFc) showed low annualized bleed rates in males aged 12 and older with severe hemophilia B when administered every 7 to over 14 days.
  • A post-hoc analysis evaluated the efficacy of rFIXFc with a ≥14-day dosing interval in 22 patients, confirming effective bleed control with low annualized bleed rates (ABRs).
  • The findings suggest that a ≥14-day dosing schedule is safe and well-tolerated, allowing some patients to manage their condition effectively with fewer injections, reducing treatment burden while maintaining effective bleed suppression.
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Background: Host-associated microbial communities have important roles in tissue homeostasis and overall health. Severe perturbations can occur within these microbial communities during critical illness due to underlying diseases and clinical interventions, potentially influencing patient outcomes. We sought to profile the microbial composition of critically ill mechanically ventilated patients, and to determine whether microbial diversity is associated with illness severity and mortality.

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Unlabelled: Pregnancy is accompanied by maternal physiological adaptations including metabolic, endocrine, immune, cardiovascular, skeletomuscular and neurological modifications that facilitate fetal and placental growth and development. Emerging evidence suggests that the maternal intestinal microbiota is modified over the course of healthy pregnancy. We have recently identified a maternal intestinal microbial shift within hours of conception; a shift that continued with advancing gestation.

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Levels of inflammatory mediators in circulation are known to increase with age, but the underlying cause of this age-associated inflammation is debated. We find that, when maintained under germ-free conditions, mice do not display an age-related increase in circulating pro-inflammatory cytokine levels. A higher proportion of germ-free mice live to 600 days than their conventional counterparts, and macrophages derived from aged germ-free mice maintain anti-microbial activity.

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The Invasion Locus () was first described in and , where it has been implicated in virulence. The two-component peptide signaling system consists of the SilA response regulator and SilB histidine kinase along with the SilCR signaling peptide and SilD/E export/processing proteins. The presence of an associated bacteriocin region suggests this system may play a role in competitive interactions with other microbes.

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Background: Alkaptonuria (AKU) is a serious genetic disease due to a defect in tyrosine metabolism, leading to increased serum levels of homogentisic acid (HGA). Nitisinone decreases HGA in AKU, but the concentration-response relationship has not been previously reported.

Objectives: To determine the relationship between serum concentrations of nitisinone and the effect on both HGA and tyrosine; secondly to determine steady-state pharmacokinetics of nitisinone in AKU patients.

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