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Clinics (Sao Paulo, Brazil) 2024To analyze whether infants admitted to hospital with Acute Viral Bronchiolitis (AVB), who received glucocorticoids and bronchodilators, and who had an atopic phenotype,...
OBJECTIVE
To analyze whether infants admitted to hospital with Acute Viral Bronchiolitis (AVB), who received glucocorticoids and bronchodilators, and who had an atopic phenotype, spent less time in hospital and/or less time on oxygen therapy when compared to those who did not have the phenotype.
METHOD
A cross-sectional, retrospective epidemiological study was developed with data from medical records of infants admitted to hospital due to AVB from 2012 to 2019 in a sentinel public hospital. It was verified that the frequency of prescription of glucocorticoids, bronchodilators and antibiotics. Length of stay and oxygen therapy duration were then compared in the group that used glucocorticoids and bronchodilators between those who had a personal or family history of atopy and those who did not. Subsequently, the length of hospital stay was compared among infants who received antibiotic therapy and those who did not.
RESULTS
Fifty-eight infants were included. Of these, 62.1 % received an antibiotic, 100 % a bronchodilator and 98.3 % a glucocorticoid. When comparing infants without a family history of atopy, those who received antibiotics had a longer hospital stay (p = 0.01).
CONCLUSION
The presence of an atopic phenotype did not interfere with the length of stay and/or oxygen therapy duration of those who received bronchodilators and glucocorticoids. Increased length of stay of infants without a family history of atopy, who used antibiotics without evidence of bacterial co-infection, and the high frequency of prescription of non-recommended drugs call attention to stricter protocol implementation and professional training in AVB diagnosis and care.
Topics: Humans; Bronchodilator Agents; Glucocorticoids; Male; Retrospective Studies; Cross-Sectional Studies; Bronchiolitis, Viral; Female; Infant; Length of Stay; Phenotype; Acute Disease; Anti-Bacterial Agents; Oxygen Inhalation Therapy; Treatment Outcome
PubMed: 38843677
DOI: 10.1016/j.clinsp.2024.100396 -
Biomedical Research (Tokyo, Japan) 2024Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function...
Mixed lymphocyte culture under the blockade of CD80/CD86-CD28 co-stimulation induces anergic (completely hyporesponsive) T cells with immune suppressive function (inducible suppressing T cells: iTS cells). Previously, iTS cell therapy has demonstrated outstanding benefits in clinical trials for organ transplantation. Here, we examined whether peptide antigen-specific iTS cells are inducible. DO 11.10 iTS cells were obtained from splenocytes of BALB/c DO 11.10 mice by stimulation with OVA peptide and antagonistic anti-CD80/CD86 mAbs. When DO 11.10 iTS or Foxp3- DO 11.10 iTS cells were stimulated with OVA, these cells produced IL-13, but not IL-4. DO 11.10 iTS cells decreased IL-4 and increased IL-13 production from OVA-stimulated naïve DO 11.10 splenocytes. When Foxp3+ DO 11.10 iTS cells were prepared, these cells significantly inhibited the production of IL-4 and IL-13 compared with freshly isolated Foxp3+ DO 11.10 T cells. Moreover, an increase in the population expressing OX40, ICOS, and 4-1BB suggested activation of Foxp3+ DO 11.10 iTS cells. Thus, blockade of CD80/CD86-CD28 co-stimulation during peptide antigen stimulation augments the inhibitory function of Foxp3+ regulatory T cells, and does not induce anergic Foxp3- conventional T cells. Peptide-specific Foxp3+ regulatory iTS cells could be useful for the treatment of allergic and autoimmune diseases without adverse effects.
Topics: Animals; T-Lymphocytes, Regulatory; CD28 Antigens; Mice; B7-1 Antigen; B7-2 Antigen; Mice, Inbred BALB C; Forkhead Transcription Factors; Peptides; Lymphocyte Activation; Interleukin-4; Interleukin-13; Ovalbumin; Spleen; Antibodies, Monoclonal
PubMed: 38839354
DOI: 10.2220/biomedres.45.115 -
Turkish Journal of Medical Sciences 2024Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with...
BACKGROUND/AIM
Data on the prevalence of allergic diseases in children with proven drug allergies are limited. We aim to evaluate the frequency of allergic comorbidity in children with proven common drug allergies.
MATERIALS AND METHODS
Children with drug hypersensitivity confirmed by diagnostic allergy tests at our center between January 2010 and December 2020 were screened retrospectively. Patients with the most common drug allergies (due to antibiotics, nonsteroidal antiinflammatory drugs [NSAIDs], and antiepileptic drugs) were selected for analysis. Age, sex, the culprit drug, initial reaction characteristics, diagnostic test results, and the study physician who diagnosed concomitant allergic diseases were noted.
RESULTS
A total of 168 patients (boys, 51.2%) with a median age of 12 years (IQR = 8-16.3) were included in the study. The culprit drug was an antibiotic in 63% (n = 106), NSAID in 25% (n = 42) and anticonvulsant in 11.9 % (n = 20) of the patients. Drug hypersensitivity reactions were immediate in 74.4 % (n = 125) and delayed in 25.6 % (n = 43) of the patients. Seventy-five patients (44.6 %) had at least one allergic disease, most commonly rhinitis (27.3 %, n = 46) or asthma (25 %, n = 42). Fifty-five patients underwent skin prick tests with aeroallergens, producing a positive result in 60% (n = 31). The prevalence of allergic disease was not differing according to the culprit drug. The frequency of developing at least one concomitant allergic disease was 47.2% (n = 50/106) for antibiotic hypersensitivity, 52.4% (n = 22/42) for NSAID hypersensitivity, and 15% (n = 3/20) for anticonvulsant hypersensitivity (p < 0.00).Immediate drug hypersensitivity reactions were more frequent in children who had allergic diseases (80 % vs. 64.5 %; p = 0.027).
CONCLUSION
Nearly half (44.6%) of the children with proven drug hypersensitivity had concomitant allergic diseases and immediate reactions were more common in this group. Children evaluated for drug hypersensitivity should be assessed for other allergic diseases.
Topics: Humans; Child; Male; Drug Hypersensitivity; Female; Retrospective Studies; Adolescent; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Anti-Bacterial Agents; Prevalence; Asthma; Comorbidity
PubMed: 38812629
DOI: 10.55730/1300-0144.5793 -
American Journal of Ophthalmology Case... Sep 2024This case report highlights a possible association between netarsudil use and crystalline keratopathy.
PURPOSE
This case report highlights a possible association between netarsudil use and crystalline keratopathy.
OBSERVATIONS
Presented here is the case of a 72-year-old woman with primary open-angle glaucoma (POAG) who developed corneal crystalline keratopathy after taking netarsudil for 24 months. The patient's medical history was significant for dry eye syndrome, bilateral ptosis with surgical repair, and atopy (including asthma and various ocular and systemic allergies). The patient had previously undergone surgical repair for bilateral ptosis as well. During the interval between two routine visits, this patient experienced worsening vision with associated eye irritation. Further examination revealed crystal deposits on the anterior corneal surface in the left eye, the only eye undergoing netarsudil treatment.
CONCLUSIONS AND IMPORTANCE
Long-term netarsudil use may be associated with crystalline keratopathy in the anterior stroma, with the potential to cause sight-threatening vision loss if located in the visual axis.
PubMed: 38799226
DOI: 10.1016/j.ajoc.2024.102069 -
MedRxiv : the Preprint Server For... May 2024Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at...
IMPORTANCE
Development of new therapies in melanoma has increased survival, and as a result more patients are living to develop brain metastasis (BrM). Identifying patients at increased risk of BrM is therefore of significant public health importance.
OBJECTIVE
To determine whether history of atopy is associated with improved survival or reduced incidence of BrM in cutaneous melanoma.
DESIGN
A retrospective cohort study conducted from June 2022 to March 2024.
SETTING
Population-based in states with Surveillance, Epidemiology and End Results (SEER) supported cancer registries.
PARTICIPANTS
Individuals (≥65 years) diagnosed with cutaneous melanoma between January 1, 2008 and December 31, 2017 that are participants in traditional Medicare.
EXPOSURES
Individuals were compared that had history of atopy (allergic rhinitis, atopic dermatitis, asthma, and/or allergic/atopic conjunctivitis) diagnosed prior to melanoma diagnosis, ascertained using ICD-9 or ICD-10 codes in Medicare claims.
MAIN OUTCOMES AND MEASURES
Primary endpoints were diagnosis with a BrM or death during the follow-up period. Associations between atopy and endpoints were assessed using cox proportional hazards models to estimate hazard ratios (HR) and p-values.
RESULTS
A total of 29,956 cutaneous melanoma cases were identified (median age 76, 60% male and 97% non-Hispanic White). Overall, 7.1% developed BrM during follow up. Among the 35% that had history of atopy, the most common condition was atopic dermatitis (19%). After adjustment for demographic and prognostic factors, atopy was associated with a 16% decrease in death (HR=0.84 [95%CI:0.80-0.87], p<0.001). Among those with non-metastatic disease at time of diagnosis, atopy conferred a 15% decrease in cumulative incidence BrM (HR=0.85 [95%CI: 0.76-0.94], p=0.006), with a 25% decrease associated with atopic dermatitis (HR=0.75 [95%CI:0.65-0.86], p<0.001). Among those with metastatic disease at diagnosis (any metastatic site), only those who received immune checkpoint inhibitors had a survival benefit associated with atopy (HR=0.31, [95%CI:0.15-0.64], p=0.001 vs HR=1.41, [95%CI:0.87-2.27], p=0.165).
CONCLUSIONS AND RELEVANCE
Atopy, particularly atopic dermatitis, was significantly associated with improved survival and decreased incidence of BrM. The improved survival associated with these conditions in the context of immunotherapy suggests that these conditions in the elderly may identify those with more robust immune function that may be more responsive to treatment.
PubMed: 38798534
DOI: 10.1101/2024.05.15.24307061 -
PloS One 2024Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral... (Comparative Study)
Comparative Study
Differential white blood cell counts are frequently used in diagnosis, patient stratification, and treatment selection to optimize therapy responses. Referral laboratories are often used but challenged with use of different hematology platforms, variable blood shipping times and storage conditions, and the different sensitivities of specific cell types. To extend the scientific literature and knowledge on the temporal commutability of blood samples between hematology analyzers, we performed a comparative ex-vivo study using four of the most utilized commercial platforms, focusing on the assessment of eosinophils given its importance in asthma management. Whole blood from healthy volunteers with and without atopy (n = 6+6) and participants with eosinophilic asthma (n = 6) were stored under different conditions (at 4, 20, 30, and 37°C, with or without agitation) and analyzed at different time points (3, 6, 24, 48 and 72h post-sampling) in parallel on the Abbott CELL-DYN Sapphire, Beckman Coulter DxH900, Siemens ADVIA 2120i and Sysmex XN-1000V. In the same blood samples, eosinophil-derived neurotoxin (EDN), eosinophil activation and death markers were analyzed. All platforms gave comparable measurements of cell differentials on fresh blood within the same day of sampling. However, by 24 hours, significant temporal and temperature-dependent differences were observed, most markedly for eosinophils. None of the platforms performed perfectly across all temperatures tested during the 72 hours, showing that handling conditions should be optimized depending on the cell type of interest and the hematology analyzer. Neither disease status (healthy vs. asthma) nor agitation of the sample affected the cell quantification result or EDN release. The eosinophil activation markers measured by flow cytometry increased with time, were influenced by temperature, and were higher in those with asthma versus healthy participants. In conclusion, hematology analyzer, time window from sampling until analysis, and temperature conditions must be considered when analyzing blood cell differentials, particularly for eosinophils, via central labs to obtain counts comparable to the values obtained in freshly sampled blood.
Topics: Humans; Asthma; Eosinophils; Female; Male; Adult; Blood Cell Count; Leukocyte Count; Middle Aged; Hematology
PubMed: 38787860
DOI: 10.1371/journal.pone.0301845 -
Journal of Fungi (Basel, Switzerland) May 2024Gut bacterial alterations have been previously linked to several non-communicable diseases in adults, while the association of mycobiome is not well understood in these...
Gut bacterial alterations have been previously linked to several non-communicable diseases in adults, while the association of mycobiome is not well understood in these diseases, especially in infants and children. Few studies have been conducted on the association between gut mycobiome and non-communicable diseases in children. We investigated gut mycobiome composition using 194 faecal samples collected at birth, 6 months after birth, and 18 months after birth in relation to atopic dermatitis (AD) and overweight diagnoses at the age of 18 or 36 months. The mycobiome exhibited distinct patterns, with prevalent in the meconium samples of both overweight and non-overweight groups. took precedence in overweight cases at 6 and 18 months, while dominated non-overweight samples at 6 months. emerged as a consistent high-abundance taxon across groups that had dermatitis and were overweight. We found a weak association between gut mycobiome and AD at birth and overweight at 18 months when using machine learning (ML) analyses. In ML, unidentified fungi, , and , were important for classifying AD, while , and were important for classifying overweight. Gut mycobiome might be associated with the development of AD and overweight in children.
PubMed: 38786688
DOI: 10.3390/jof10050333 -
International Journal of Trichology 2023Alopecia totalis (AT) and Alopecia universalis (AU) are forms of Alopecia areata (AA) which represent the strongest predictor of poor prognosis since spontaneous...
INTRODUCTION
Alopecia totalis (AT) and Alopecia universalis (AU) are forms of Alopecia areata (AA) which represent the strongest predictor of poor prognosis since spontaneous regrowth is <10%. Topical immunotherapy agent, diphenylcyclopropenone (DPCP) has shown clinical efficacy with limited side effects in severe forms of AA. However, its specific role in AT/AU characterized by complete hair loss over the scalp can help highlight the efficacy of the drug with fewer confounders.
METHODOLOGY
Data were collected from 18 patients diagnosed with AT/AU and treated with topical immunotherapy with DPCP as per protocol by Happle . Baseline Severity of Alopecia Tool (SALT) score and subclass was recorded. In the case of AU, baseline body hair loss score was also recorded. Patients were reassessed after 6 months of treatment in terms of change in SALT score and hair regrowth was assessed using the Global Assessment Score. The side effects during treatment were also assessed and recorded.
RESULTS
Eighteen patients of whom eleven (61.1%) were diagnosed as AU and seven (38.9%) as AT were treated. The mean age was 21.6, with a male: female ratio of 3:2. The comorbidities noted were atopy in six (33.3%), atopy and hypothyroidism in one (5.5%), Down's syndrome in two (11.1%), and hypothyroidism alone in one (5.5%) patient. The mean duration of disease at the time of presentation was 3 years and all patients had remained refractory to various other modalities of treatment. All patients had a baseline SALT score of 100 corresponding to S5. After 6 months of treatment, 27.7% of patients did not show any response (SALT score S5), 16.6% had a score of S4, 11.1% had a score of S3, 11.1% had a score of S2, 22.2% had a score of S1, and 11.1% had a score of S0. On assessing improvement in body hair loss score, 36.3% of patients showed no improvement, 36.3% showed partial improvement, and 27.2% of patients showed complete body hair regrowth. About 55.5% of patients developed notable side effects that included severe local reactions, cervical lymphadenopathy, acne and pigmentation at the site of application as well as untreated sites.
CONCLUSION
The AT/AU subtypes of AA, was amenable to treatment with contact immunotherapeutic agent DPCP with a >75% hair regrowth in 33.3% of patients. The castling phenomenon was seen in 63.6% of AU patients. The adverse effects noted were not severe enough to deter treatment.
PubMed: 38765726
DOI: 10.4103/ijt.ijt_2_22 -
The Journal of Allergy and Clinical... Aug 2024The KIT receptor tyrosine kinase and its ligand, stem cell factor (SCF), control proliferation and survival of mast cells. Thus, targeting KIT signaling may show promise...
BACKGROUND
The KIT receptor tyrosine kinase and its ligand, stem cell factor (SCF), control proliferation and survival of mast cells. Thus, targeting KIT signaling may show promise for the treatment of allergic diseases involving mast cells. Recently, we discovered a new compound, MOD000001, as a potential small-molecule KIT kinase inhibitor by using an approach.
OBJECTIVE
We sought to determine whether MOD000001 is highly selective to KIT, inhibits KIT signaling in mast cells, and affects IgE-mediated mast cell activation.
METHODS
The interaction of MOD000001 with 468 human kinases and its inhibitory activity against KIT were profiled and evaluated by using KINOMEscan (Discover X/Eurofins Corporation, Fremont, Calif) and cell-free kinase assays, respectively. The effects of MOD000001 on SCF-dependent signaling were examined by using primary mouse and human mast cells. The effects of MOD000001 on SCF-induced degranulation and passive cutaneous anaphylaxis reaction were examined in mice.
RESULTS
MOD000001 interacted with KIT and inhibited KIT kinase activity with high selectivity. MOD000001 suppressed SCF-induced KIT signaling in mouse and human mast cells and in mice. Passive cutaneous anaphylaxis reaction was suppressed in mice treated with MOD000001 both for a short-term (1 week) and for a long-term (7 weeks). Mice treated with MOD000001 for a long-term, but not for a short-term, showed skin mast cell reduction.
CONCLUSIONS
MOD000001 is a highly selective KIT inhibitor that can suppress IgE-mediated mast cell activation . MOD000001 may do so by reducing tissue mast cell numbers or by other unknown mechanisms. The findings suggest potential benefits of MOD000001 for allergic diseases involving IgE-mediated mast cell activation.
PubMed: 38764489
DOI: 10.1016/j.jacig.2024.100249