-
European Annals of Allergy and Clinical... Jun 2024Pediatric cutaneous mastocytosis patients diagnosed and followed up by our specialist were enrolled in this study, and clinical and laboratory evaluations were...
Pediatric cutaneous mastocytosis patients diagnosed and followed up by our specialist were enrolled in this study, and clinical and laboratory evaluations were retrospectively analyzed from patients' archived files. Patients, who applied to the Division of Pediatric Allergy And Immunology Unit of a University Training and Research Hospital between 01.01.2010 and 28.04.2021, were enrolled in this study. Of the 33 patients included in the study, 11 (33.3%) were female and 22 (67.7%) were male. The median age of onset of the patient's complaints was 7 (0-60) months. The median age at diagnosis was 11 (2-64) months. Their complaints' median regression age was 54 (6-192) months. Resistant clinical findings were followed in 13 (39.4%) patients. Itching, redness, gastrointestinal symptoms, and maculopapular eruption were the most common complaints. The rashes were mostly polymorphic and larger than 1 cm. Heat was the most common trigger. Darier's sign was positive in 97% of the patients. Antihistamines were the most commonly used drug for prophylaxis and treatment. The autoinjector prescription rate was 24.2%. Quality of life was mildly affected in 48,5% of the patients based on the CDLQI scores. Thus, patients should be followed up through adolescence for the development of systemic signs and symptoms.
PubMed: 38913387
DOI: 10.23822/EurAnnACI.1764-1489.348 -
Journal of Cancer 2024In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach....
In this study, we aimed to elucidate the role of mitochondrial calcium uptake 1/2 (MiCU1/2) in breast cancer (BRCA) by employing a comprehensive multi-omics approach. Unlike previous research, we utilized a novel web application tailored for whole tumor tissue, single-cell, and spatial transcriptomics analysis to investigate the association between MiCU1/2 and the tumor immune microenvironment (TIME). Our gene set enrichment analysis (GSEA) provided insights into the primary biological effects of MiCU1/2, while our CRISPR-based drug screening repository identified potential effective drugs. Our study revealed that high MiCU1/2 expression serves as an independent diagnostic biomarker, correlating with advanced clinical status and indicating poorer recurrence-free survival (RFS) rates in BRCA patients. Additionally, spatial transcriptome analysis highlighted the heightened expression of MiCU1/2 in tumors and its relevance in surrounding immune cells. Furthermore, using the CIBERSORT algorithm, we discovered a positive correlation between MiCU1/2 levels and macrophage infiltration, underscoring their potential impact on immune infiltration. We also identified expression patterns of immune-related genes associated with responses against various immune cell types, including CXCL, MIF, GDF, SPP1, and IL16. Finally, our pharmacogenomic screening identified potential small molecule drugs capable of effectively targeting breast cancer cells with elevated MiCU1/2 expression. Overall, our study establishes MiCU1/2 as a promising novel biomarker for BRCA diagnosis and prognostic prediction, as well as a potential therapeutic target, highlighting the importance of exploring these pathways to advance patient care and outcomes in BRCA treatment.
PubMed: 38911376
DOI: 10.7150/jca.95979 -
Allergy, Asthma & Immunology Research May 2024The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled...
The diagnosis of anaphylaxis is based on the clinical history. The utility of tryptase measurements in clinical setting is limited. Mas-related G protein-coupled receptor-X2 (MRGPRX2) is expressed in mast cells and is involved in the degranulation of these cells. We evaluated the potential of MRGPRX2 as a diagnostic biomarker in patients with iodinated contrast media (ICM)-induced immediate hypersensitivity reactions (IHRs). A total of 173 patients with documented ICM-induced IHR within 4 months from registration were enrolled and skin tests for the culprit ICM were performed. The time interval was evaluated as the duration between the onset of ICM-induced IHR and the measurement of serum MRGPRX2 levels. Serum MRGPRX2 concentration was determined using an enzyme-linked immunosorbent assay kit. Of the 173 patients, 33 and 140 were included in the anaphylaxis and non-anaphylaxis groups, respectively. Serum MRGPRX2 levels were significantly higher in the anaphylaxis than in the non-anaphylaxis group (29.9 ± 24.1 vs. 20.7±17.5, = 0.044). Serum MRGPRX2 showed a moderate predictive ability for anaphylaxis, with an area under the curve of 0.61 ( = 0.058). When groups were classified based on the time interval, T1(0-2months) and T2 (2-4months), patients with anaphylaxis had higher MRGPRX2 levels compared to the non-anaphylaxis group in the T2 group (36.5±19.2 vs. 20.5±19.0, = 0.035). This pilot study shows that serum MRGPRX2 is a potential long-term biomarker for predicting anaphylaxis, particularly ICM-induced anaphylaxis. Further studies are needed to determine the role of MRGPRX2 in anaphylaxis in a larger population of patients with various drug-induced IHRs.
PubMed: 38910288
DOI: 10.4168/aair.2024.16.3.308 -
BMC Pediatrics Jun 2024Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly...
BACKGROUND
Serum Sickness-Like Reaction (SSLR) is an immune response characterized by rash, polyarthralgias, inflammation, and fever. Serum sickness-like reaction is commonly attributed to antibiotics, anticonvulsants, and anti-inflammatory agents.
CASE PRESENTATION
A 16-year-old female with a history of overactive bladder and anemia presented with a diffuse urticarial rash, headaches, joint pain, and swelling for three days. Her medications included oral contraceptive pills, iron, mirabegron, UQora, and a probiotic. Physical examination revealed a diffuse urticarial rash, and her musculoskeletal exam revealed swelling and tenderness in her wrists. She was evaluated by her pediatrician and started on a 7-day course of prednisone, as well as antihistamines. Her CBC, basic metabolic panel, liver function panel, Lyme titers, and urinalysis were all within normal limits. With concern for hypersensitivity reaction to medication, all medications were discontinued. Nine days after symptom onset, the patient was evaluated by an allergist, who confirmed her presentation was consistent with serum sickness-like reaction. Her symptoms resolved, and her medications were re-introduced sequentially over several months. Restarting UQora, however, triggered a recurrence of her symptoms, and it was identified as the culprit medication. Consequently, UQora was permanently discontinued, and the patient has remained symptom-free.
CONCLUSIONS
This case report describes the first documented case of serum sickness-like reaction caused by UQora (active ingredient D-mannose). D-mannose is a monosaccharide, and it is frequently promoted to prevent urinary tract infections. While the clinical features and timeline in this case were typical of serum sickness-like reaction, UQora as the trigger was highly unusual. Clinicians should be aware of the diverse triggers of serum sickness-like reaction and the importance of prompt identification and management to enhance patient safety. Further research is necessary to better understand the potential therapeutic applications of D-mannose, as well as the potential risks and interactions.
Topics: Humans; Female; Serum Sickness; Adolescent
PubMed: 38909179
DOI: 10.1186/s12887-024-04753-8 -
The Journal of Allergy and Clinical... Jun 2024Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and... (Review)
Review
Asthma is a leading worldwide biomedical concern. Patients can experience life-threatening worsening episodes (exacerbations) usually controlled by anti-inflammatory and bronchodilator drugs. However, substantial heterogeneity in treatment response exists and a subset of patients with unresolved asthma carry the major burden of this disease. The study of the epigenome and microbiome might bridge the gap between human genetics and environmental exposures to partially explain the heterogeneity in drug response. This review aims to provide a critical examination of the existing literature on the microbiome and epigenetic studies examining associations with asthma treatments and drug response, highlight convergent pathways, address current challenges, and offer future perspectives. Current epigenetic and microbiome studies have shown the bilateral relationship between asthma pharmacological interventions and the human epigenome and microbiome. These studies, focusing on corticosteroids and to a lesser extent on bronchodilators, azithromycin, immunotherapy, and mepolizumab, have improved the understanding of the molecular basis of treatment response and identified promising biomarkers for drug response prediction. Immune and inflammatory pathways (i.e., IL-2, TNF-α, NF-κB, and CEBPs) underlie microbiome-epigenetic associations with asthma treatment, representing potential therapeutic pathways to be targeted. A comprehensive evaluation of these omic biomarkers could significantly contribute to precision medicine and new therapeutic target discovery.
PubMed: 38906272
DOI: 10.1016/j.jaci.2024.06.010 -
World Journal of Clinical Cases Jun 2024() eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and...
BACKGROUND
() eradication rates have fallen globally, likely in large part due to increasing antibiotic resistance to traditional therapy. In areas of high clarithromycin and metronidazole resistance such as ours, Maastricht VI guidelines suggest high dose amoxicillin dual therapy (HDADT) can be considered, subject to evidence for local efficacy. In this study we assess efficacy of HDADT therapy for eradication in an Irish cohort.
AIM
To assess the efficacy of HDADT therapy for eradication in an Irish cohort as both first line, and subsequent therapy for patients diagnosed with .
METHODS
All patients testing positive for in a tertiary centre were treated prospectively with HDADT (amoxicillin 1 g and esomeprazole 40 mg × 14 d) over a period of 8 months. Eradication was confirmed with Urea Breath Test at least 4 wk after cessation of therapy. A delta-over-baseline > 4% was considered positive. Patient demographics and treatment outcomes were recorded, analysed and controlled for basic demographics and prior treatment.
RESULTS
One hundred and ninety-eight patients were identified with infection, 10 patients were excluded due to penicillin allergy and 38 patients refused follow up testing. In all 139 were included in the analysis, 55% ( = 76) were female, mean age was 46.6 years. Overall, 93 (67%) of patients were treatment-naïve and 46 (33%) had received at least one previous course of treatment. The groups were statistically similar. Self-reported compliance with HDADT was 97%, mild side-effects occurred in 7%. There were no serious adverse drug reactions. Overall the eradication rate for our cohort was 56% (78/139). Eradication rates were worse for those with previous treatment [43% (20/46) 62% (58/93), = 0.0458, odds ratio = 2.15]. Age and Gender had no effect on eradication status.
CONCLUSION
Overall eradication rates with HDADT were disappointing. Despite being a simple and possibly better tolerated regime, these results do not support its routine use in a high dual resistance country. Further investigation of other regimens to achieve the > 90% eradication target is needed.
PubMed: 38899284
DOI: 10.12998/wjcc.v12.i16.2773 -
ALTEX May 2024The webinar series and workshop titled Trust Your Gut: Establishing Confidence in Gastrointestinal Models - An Overview of the State of the Science and Contexts of Use...
The webinar series and workshop titled Trust Your Gut: Establishing Confidence in Gastrointestinal Models - An Overview of the State of the Science and Contexts of Use was co-organized by NICEATM, NIEHS, FDA, EPA, CPSC, DoD, and the Johns Hopkins Center for Alternatives to Animal Testing (CAAT) and hosted at the National Institutes of Health in Bethesda, MD, USA on October 11-12, 2023. New approach methods (NAMs) for assessing issues of gastrointestinal tract (GIT)-related toxicity offer promise in addressing some of the limitations associated with animal-based assessments. GIT NAMs vary in complexity, from two-dimensional monolayer cell line-based systems to sophisticated 3-dimensional organoid systems derived from human primary cells. Despite advances in GIT NAMs, challenges remain in fully replicating the complex interactions and processes occurring within the human GIT. Presentations and discussions addressed regulatory needs, challenges, and innovations in incorporating NAMs into risk assessment frameworks; explored the state of the science in using NAMs for evaluating systemic toxicity, understanding absorption and pharmacokinetics, evaluating GIT toxicity, and assessing potential allergenicity; and discussed strengths, limitations, and data gaps of GIT NAMs as well as steps needed to establish confidence in these models for use in the regulatory setting.
PubMed: 38898799
DOI: 10.14573/altex.2403261 -
Nature Communications Jun 2024Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we...
Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions.
Topics: Biological Products; Drug Discovery; Metabolomics; Microbiota; Metagenomics; Magnetic Resonance Spectroscopy; Small Molecule Libraries
PubMed: 38898025
DOI: 10.1038/s41467-024-49367-x -
ELife Jun 2024Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying...
Spinal pain affects individuals of all ages and is the most common musculoskeletal problem globally. Its clinical management remains a challenge as the underlying mechanisms leading to it are still unclear. Here, we report that significantly increased numbers of senescent osteoclasts (SnOCs) are observed in mouse models of spinal hypersensitivity, like lumbar spine instability (LSI) or aging, compared to controls. The larger population of SnOCs is associated with induced sensory nerve innervation, as well as the growth of H-type vessels, in the porous endplate. We show that deletion of senescent cells by administration of the senolytic drug Navitoclax (ABT263) results in significantly less spinal hypersensitivity, spinal degeneration, porosity of the endplate, sensory nerve innervation, and H-type vessel growth in the endplate. We also show that there is significantly increased SnOC-mediated secretion of Netrin-1 and NGF, two well-established sensory nerve growth factors, compared to non-senescent OCs. These findings suggest that pharmacological elimination of SnOCs may be a potent therapy to treat spinal pain.
Topics: Animals; Mice; Osteoclasts; Cellular Senescence; Sensory Receptor Cells; Disease Models, Animal; Male; Nerve Growth Factor; Netrin-1; Mice, Inbred C57BL
PubMed: 38896465
DOI: 10.7554/eLife.92889 -
Clinical, Cosmetic and Investigational... 2024Zoledronic acid is a bisphosphonate that can be administered intravenously and used to treat several bone disorders. It decreases bone resorption, thereby improving bone...
Zoledronic acid is a bisphosphonate that can be administered intravenously and used to treat several bone disorders. It decreases bone resorption, thereby improving bone mineral density (BMD) and reducing fractures. The Food and Drug Administration (FDA) has approved zoledronic acid for the prevention and treatment of osteoporosis in postmenopausal females and males and for other conditions. Zoledronic acid is generally well tolerated, with most side effects being musculoskeletal or gastrointestinal. Cutaneous side effects include maculopapular rash and other mild skin reactions. Rare severe skin rashes, such as toxic epidermal necrolysis, have been reported. Here, we report the case of a 64-year-old female with a medical history of breast cancer status post-radical mastectomy and chemotherapy presenting with delayed hypersensitivity reaction to a hyaluronic acid dermal filler two days after receiving zoledronic acid intravenously given to maintain bone density, symptoms completely resolved with oral prednisolone 20 mg once daily and cetirizine 10 mg. Cases of delayed inflammatory reaction to hyaluronic acid soft tissue filler have previously been reported in patients who have received vaccination or those with viral infections. However, to our knowledge, there have been no reports of delayed inflammatory reactions to facial hyaluronic acid injections after zoledronic acid administration.
PubMed: 38895606
DOI: 10.2147/CCID.S458750