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1.
Am J Gastroenterol ; 119(2): 262-269, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37782465

RESUMO

INTRODUCTION: Differences in eosinophilic esophagitis (EoE) presentation and outcomes by ethnicity or race remain understudied. We aimed to determine whether EoE patients of Hispanic/Latinx ethnicity or non-White race have differences in presentation at diagnosis or response to topical corticosteroid (tCS) treatment. METHODS: This retrospective cohort study included subjects of any age with a new diagnosis of EoE and documentation of ethnicity or race. For those who had treatment with tCS and follow-up endoscopy/biopsy, we assessed histologic response (<15 eosinophils/hpf), global symptom response, and endoscopic response. Hispanic EoE patients were compared with non-Hispanics at baseline and before and after treatment. The same analyses were repeated for White vs non-Whites. RESULTS: Of 1,026 EoE patients with ethnicity data, just 23 (2%) were Hispanic. Most clinical features at presentation were similar to non-Hispanic EoE patients but histologic response to tCS was numerically lower (38% vs 57%). Non-White EoE patients (13%) were younger at diagnosis and had less insurance, lower zip code-level income, shorter symptom duration, more vomiting, less dysphagia and food impaction, fewer typical endoscopic features, and less dilation. Of 475 patients with race data treated with tCS, non-Whites had a significantly lower histologic response rate (41% vs 59%; P = 0.01), and odds of histologic response remained lower after controlling for potential confounders (adjusted odds ratio 0.40, 95% confidence intervals: 0.19-0.87). DISCUSSION: Few EoE patients at our center were Hispanic, and they had similar clinical presentations as non-Hispanics. The non-White EoE group was larger, and presentation was less dysphagia-specific. Non-White patients were also less than half as likely to respond to tCS.


Assuntos
Transtornos de Deglutição , Enterite , Eosinofilia , Esofagite Eosinofílica , Gastrite , Humanos , Esofagite Eosinofílica/diagnóstico , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Minorias Étnicas e Raciais , Esteroides/uso terapêutico , Glucocorticoides/uso terapêutico
2.
Clin Gastroenterol Hepatol ; 21(10): 2483-2495.e1, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-36731590

RESUMO

BACKGROUND & AIMS: Several studies have been published on the association between food processing and risks of Crohn's disease (CD) and ulcerative colitis (UC), with some variability in results. We performed a systematic literature review and meta-analysis to study this association. METHODS: From PubMed, Medline, and Embase until October 2022, we identified cohort studies that studied the association between food processing and the risk of CD or UC. Risk of bias of the included studies was assessed by the Newcastle-Ottawa scale. We computed pooled hazard ratios (HRs) and 95% confidence intervals (CIs) using random-effects meta-analysis based on estimates and standard errors. RESULTS: A total of 1,068,425 participants were included (13,594,422 person-years) among 5 cohort studies published between 2020 and 2022. Four of the 5 included studies were scored as high quality. The average age of participants ranged from 43 to 56 years; 55%-83% were female. During follow-up, 916 participants developed CD, and 1934 developed UC. There was an increased risk for development of CD for participants with higher consumption of ultra-processed foods compared with those with lower consumption (HR, 1.71; 95% CI, 1.37-2.14; I2 = 0%) and a lower risk of CD for participants with higher consumption of unprocessed/minimally processed foods compared with those with lower consumption (HR, 0.71; 95% CI, 0.53-0.94; I2 = 11%). There was no association between risk of UC and ultra-processed foods (HR, 1.17; 95% CI, 0.86-1.61; I2 = 74%) or unprocessed/minimally processed foods (HR, 0.84; 95% CI, 0.68-1.02; I2 = 0%). CONCLUSIONS: Higher ultra-processed food and lower unprocessed/minimally processed food intakes are associated with higher risk of CD but not UC.


Assuntos
Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Doenças Inflamatórias Intestinais/epidemiologia , Risco , Manipulação de Alimentos
3.
Clin Gastroenterol Hepatol ; 21(9): 2252-2259.e3, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-36410644

RESUMO

BACKGROUND & AIMS: Understanding which eosinophilic esophagitis (EoE) patients will respond to treatment with topical corticosteroids (tCS) remains challenging, and it is unknown whether obesity impacts treatment response. This study aimed to determine whether treatment outcomes to tCS in EoE patients vary by body mass index (BMI). METHODS: This retrospective cohort study of the University of North Carolina EoE Clinicopathologic database assessed subjects age 14 years or older with a new diagnosis of EoE. Their BMI was calculated and histologic, symptom, and endoscopic responses were recorded after tCS treatment. The treatment response of obese (BMI, ≥30 kg/m2) and nonobese EoE status was compared using bivariate and multivariate analyses. RESULTS: We identified 296 EoE patients treated with tCS. Baseline characteristics were similar, although obese EoE patients had more heartburn and hiatal hernias. Histologic response was higher for those who were nonobese compared with obese at fewer than 15 (61% vs 47%; P = .049) and 6 or fewer (54% vs 38%; P = .02) eosinophils per high-power field, respectively. In addition, nonobese patients had significantly greater endoscopic and symptomatic responses. On multivariate analysis, increasing BMI was associated independently with decreased histologic response after accounting for age, heartburn, dilation, and hiatal hernia whether BMI was assessed as a continuous variable (adjusted odds ratio [aOR], 0.93; 95% CI, 0.89-0.98), as nonobese vs obese (aOR, 0.38; 95% CI, 0.21-0.68), or in 4 categories (overweight vs normal [aOR, 0.46; 95% CI, 0.26-0.84] or obese vs normal [aOR, 0.26; 95% CI, 0.13-0.51]). CONCLUSIONS: As BMI increases in EoE patients, the odds of histologic, symptomatic, and endoscopic responses to tCS decreases, with obese patients having an approximately 40% decrease in odds of response.


Assuntos
Esofagite Eosinofílica , Humanos , Adolescente , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/diagnóstico , Índice de Massa Corporal , Azia/complicações , Estudos Retrospectivos , Glucocorticoides , Esteroides , Obesidade/complicações
4.
Ann Allergy Asthma Immunol ; 131(1): 109-115.e2, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37100277

RESUMO

BACKGROUND: Patients with eosinophilic esophagitis (EoE) typically have concomitant atopic conditions, but whether there are differences in presentation or treatment response by the number of atopic diseases is unknown. OBJECTIVE: To determine whether patients with EoE having multiple atopic conditions have differences in presentation or response to topical corticosteroid (TCS) treatment. METHODS: We performed a retrospective cohort study of adults and children with newly diagnosed EoE. The total number of atopic comorbidities (allergic rhinitis, asthma, eczema, food allergy) was calculated. Patients with at least 2 atopic conditions other than allergic rhinitis were defined as having multiple atopic conditions and their baseline characteristics were compared with those with less than 2 atopic conditions. Histologic, symptom, and endoscopic responses to TCS treatment were also compared with bivariable and multivariable analyses. RESULTS: Of the 1020 patients with EoE having atopic disease information, 235 (23%) had 1 atopic comorbidity, 211 (21%) had 2, 113 (11%) had 3, and 34 (3%) had 4. At baseline, the 180 (18%) patients with 2 or more atopic diseases were younger and had more vomiting, less abdominal pain, more exudates and edema on endoscopy, and higher peak eosinophil counts. Among those treated with TCS, there was a trend toward better global symptom response in patients with less than 2 atopic conditions, but there was no difference in histologic or endoscopic response compared with those with 2 or more atopic conditions. CONCLUSION: There were differences in the initial presentation of EoE between those with and without multiple atopic conditions, but there were no major differences in histologic treatment response to corticosteroids by atopic status.


Assuntos
Esofagite Eosinofílica , Hipersensibilidade Imediata , Rinite Alérgica , Criança , Adulto , Humanos , Esofagite Eosinofílica/diagnóstico , Estudos Retrospectivos , Rinite Alérgica/complicações , Corticosteroides/uso terapêutico , Esteroides/uso terapêutico
5.
Molecules ; 28(21)2023 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-37959659

RESUMO

Polydeoxyribonucleotide (PDRN) has the ability to regenerate skin cells and improve the skin barrier and wound healing. This study investigated the possibility of replacing animal-derived PDRN with plant-derived PDRN. To test this, the adventitious roots of Korean ginseng (Panax ginseng C.A. Meyer), which is commonly used to treat various diseases, were suspension-cultivated through tissue culture; subsequently, PDRN was purified using microfluidization, an ultra-high-pressure physical grinding method. The results showed that purified Panax PDRN was effective in healing skin wounds and enhancing the skin barrier. Panax PDRN promoted the proliferation of keratinocytes and fibroblasts by increasing the expression of fibronectin, filaggrin, Ki-67, Bcl-2, inhibin beta A, and Cyclin D1. It also acted as an agonist of the adenosine A2A receptor and induced the phosphorylation of focal adhesion kinase, adenosine triphosphate-dependent tyrosine kinase, and mitogen-activated protein kinase. This activated signal transduction, thereby regenerating skin cells and strengthening the barrier. These results were not only observed in skin cells but also in an artificial skin model (KeraSkinTM). The use of plant-derived PDRN instead of animal-derived PDRN can promote animal welfare and environmental sustainability. Furthermore, Panax PDRN can potentially be a new plant-derived PDRN (PhytoPDRN) that may be utilized in the treatment of various skin diseases.


Assuntos
Panax , Polidesoxirribonucleotídeos , Animais , Polidesoxirribonucleotídeos/farmacologia , Pele , Cicatrização , Queratinócitos
6.
Clin Gastroenterol Hepatol ; 20(8): 1701-1708.e2, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34718172

RESUMO

BACKGROUND & AIMS: There are few data assessing disease progression in eosinophilic esophagitis (EoE) after diagnosis. We aimed to determine outcomes and assess for progression of fibrosis in patients with EoE with a gap in their regular care. METHODS: In this retrospective cohort study of newly diagnosed patients with EoE, a "gap" in care was defined as ≥2 years without medical contact for EoE. For inclusion, a gap in care and both pre- and post-gap endoscopies were required. Patients with and without a gap were compared. Data were also compared in gap patients before the gap and after EoE care resumed, and progression of fibrosis and predictors were assessed. RESULTS: Of 701 patients with EoE, 95 (14%) had a gap in care (mean time without care, 4.8 ± 2.3 years). Post-gap, 12% presented with food impaction requiring emergency evaluation. Compared with pre-gap, patients post-gap had higher endoscopic severity (2.4 vs 1.5; P < .001) and smaller esophageal diameters (11.0 vs 12.7 mm; P = .04). Strictures were more prevalent with longer gap time (P < .05 for trend). Each additional year of gap time increased odds of stricture by 26%, even after accounting for pre-gap dilation. Additionally, of 67 patients without pre-gap fibrosis, 25 (37%) had at least one fibrotic feature (stricture, narrowing, or requiring dilation) post-gap. CONCLUSIONS: A gap in care of ≥2 years in patients with EoE was associated with signs of increased disease activity, and progression to fibrostenosis was noted, particularly with longer gaps in care. Because EoE can progress to fibrosis even after diagnosis, regular care in patients with EoE is required, perhaps at intervals <2 years.


Assuntos
Esofagite Eosinofílica , Estenose Esofágica , Constrição Patológica/complicações , Enterite , Eosinofilia , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/diagnóstico , Estenose Esofágica/diagnóstico , Fibrose , Gastrite , Humanos , Estudos Retrospectivos
7.
Endoscopy ; 54(3): 243-250, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33910259

RESUMO

BACKGROUND: Little is known about esophageal dilation as a long-term treatment approach for eosinophilic esophagitis (EoE). We examined the impact of a "dilate and wait" strategy on symptom management and safety of patients with EoE. METHODS: This retrospective cohort study included two patient groups: those who underwent a dilation-predominant approach (≥ 3 dilations as sole therapy or for histologically refractory disease [> 15 eos/hpf]); and those who had routine care (< 3 dilations or histologic response). Group characteristics were compared and outcomes for the dilation-only group assessed. RESULTS: 53/205 patients (26 %) received the dilation-predominant strategy (total 408 dilations), predominantly for histologic treatment nonresponse (75 %). These patients were younger (33 vs. 41 years; P = 0.003), had a narrower baseline esophageal diameter (9.8 vs. 11.5 mm; P = 0.005), underwent more dilations (7.7 vs. 3.4; P < 0.001), but achieved a smaller final diameter (15.7 vs. 16.7 mm; P = 0.01) vs. routine care. With this strategy, 30 patients (57 %) had ongoing symptom improvement, with esophageal caliber change independently associated with symptom response (adjusted odds ratio 1.79, 95 % confidence interval 1.16-2.78); 26 (49 %) used the strategy as a bridge to clinical trials. Over a median follow-up of 1001 days (interquartile range 581-1710), no deaths or dilation-related perforations occurred, but there were nine emergency room visits, including one for post-dilation bleeding and four for food impaction. CONCLUSIONS: A dilation-predominant long-term treatment strategy allowed for symptom control or bridge to clinical trials for patients with difficult-to-treat EoE. Close follow-up and monitoring for complications are required.


Assuntos
Esofagite Eosinofílica , Estenose Esofágica , Dilatação/efeitos adversos , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/terapia , Estenose Esofágica/etiologia , Estenose Esofágica/patologia , Estenose Esofágica/terapia , Humanos , Estudos Retrospectivos
8.
Dig Dis Sci ; 67(8): 3576-3583, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34585285

RESUMO

BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic disease, but the extent of patient loss to follow-up (LTFU) and health care utilization has not been fully investigated. AIM: To determine frequency and predictors of LTFU and health care utilization in EoE patients. METHODS: In this retrospective cohort study, we extracted data from patients with a new diagnosis of EoE. Follow-up time for each patient was calculated as the time from the first diagnostic endoscopy to the last GI-related contact date in the medical record. Patients with and without LTFU were compared, and the volume of EoE-related health care interactions was recorded. RESULTS: Of 944 EoE cases, 249 (26%) met the definition for LTFU. Major reasons for LTFU were never being scheduled (45%) and inability to contact patients (40%). Factors independently associated with regular follow-up were having insurance (aOR 2.89; 95% CI 1.85-4.50), white race (aOR 2.16; 95% CI 1.37-3.41), and longer symptom length (aOR 1.04 per year; 95% CI 1.01-1.08). At the time of last contact, patients with follow-up had better symptom response (55% vs. 12%; p < 0.001), improved esophageal caliber (14.3 vs. 12.4 mm; p = 0.005), and more histologic response (45% vs. 4% at 15 eos/hpf; p < 0.001). Health care utilization was high, with an average of 4.6 endoscopies and 4.0 clinic visits over the follow-up period. CONCLUSIONS: LTFU of newly diagnosed EoE cases was common and associated with lack of insurance, non-white race, and shorter symptom duration. Those who followed up had high health care utilization but improved response rates. Strategies are needed to help decrease LTFU in EoE.


Assuntos
Esofagite Eosinofílica , Enterite , Eosinofilia , Esofagite Eosinofílica/diagnóstico , Esofagite Eosinofílica/epidemiologia , Esofagite Eosinofílica/terapia , Seguimentos , Gastrite , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos
9.
Dis Esophagus ; 36(1)2022 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35829628

RESUMO

Eosinophilic esophagitis (EoE) has been associated with autoimmune (AI) and connective tissue disorders (CTDs), but clinical correlates and treatment response to topical corticosteroids (tCS) for patients with both conditions are not well known. We aimed to determine the prevalence and clinical features of AI/CTDs in EoE patients, and assess the response to tCS. In this retrospective cohort study of adults and children newly diagnosed with EoE in the University of North Carolina EoE Clinicopathologic database, we extracted clinical characteristics and treatment response data. We compared EoE patients with and without AI/CTDs, identified independently associated factors, and explored treatment responses. Of 1029 EoE patients, 61 (5.9%) had an AI/CTDs. The most common AI/CTDs were psoriasis/psoriatic arthritis (P/PA) (1.7%), Hashimoto's (1.2%), and rheumatoid arthritis (RA) (1%). Compared to those without AI/CTDs, AI/CTDs patients were older (35 vs. 28 years, P = 0.004), more likely to be female (51% vs. 30%, P = 0.001), have insurance (93% vs. 78%, P = 0.004) and a longer symptom duration prior to EoE diagnosis (10 vs. 7 years, P = 0.02). Older age, female sex, having insurance, and having allergic rhinitis were independently associated with AI/CTDs. AI/CTD patients with EoE were less likely to have a symptom response (47% vs. 79%, P = 0.003). Overlap between EoE and AI/CTDs was uncommon, seen in approximately 6%, with P/PA, Hashimoto's, and RA being most frequent. In conclusion, older age, female sex, having insurance, and allergic rhinitis were independently associated with AI/CTDs. EoE patients with AI/CTDs had less symptom response, with trendtowards lower endoscopic and histologic responses, to tCS therapy.


Assuntos
Esofagite Eosinofílica , Rinite Alérgica , Adulto , Criança , Humanos , Feminino , Masculino , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/epidemiologia , Estudos Retrospectivos , Rinite Alérgica/complicações , Rinite Alérgica/epidemiologia , Tecido Conjuntivo/patologia
10.
Plant Physiol ; 184(4): 1658-1673, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32887734

RESUMO

Genetic screens are powerful tools to dissect complex biological processes, but a rate-limiting step is often the cloning of targeted genes. Here, we present a strategy, "mutagenomics," to identify causal mutations from a screen in a high throughput fashion in the absence of backcrossing. Mutagenomics is initiated by sequencing the genomes of the mutants identified, which are then subjected to a three-stage pipeline. The first stage identifies sequence changes in genes previously linked to the targeted pathway. The second stage uses heuristics derived from a simulation strategy to identify genes that are represented by multiple independent alleles more often than expected by chance. The third stage identifies candidate genes for the remaining lines by sequencing multiple lines of common descent. Our simulations indicate that sequencing as few as three to four sibling lines generally results in fewer than five candidate genes. We applied mutagenomics to a screen for Arabidopsis (Arabidopsis thaliana) mutants involved in the response to the phytohormone cytokinin. Mutagenomics identified likely causative genes for many of the mutant lines analyzed from this screen, including 13 alleles of the gene encoding the ARABIDOPSIS HIS KINASE4 cytokinin receptor. The screen also identified 1-AMINOCYCLOPROPANE-1-CARBOXYLATE (ACC) SYNTHASE7, an ACC synthase homolog involved in ethylene biosynthesis, and ELONGATED HYPOCOTYL5 (HY5), a master transcriptional regulator of photomorphogenesis. HY5 was found to mediate a subset of the transcriptional response to cytokinin. Mutagenomics has the potential to accelerate the pace and utility of genetic screens in Arabidopsis.


Assuntos
Arabidopsis/genética , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Alelos , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Variação Genética
11.
Dig Dis Sci ; 66(10): 3312-3321, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33492534

RESUMO

BACKGROUND: The relationship between histologic disease activity in eosinophilic esophagitis (EoE) and generic measures of quality of life (QoL) is unclear. AIMS: To determine differences in QoL in adults with EoE based on histologic activity and assess changes in QoL over time. METHODS: We performed an analysis of prospectively collected data from patients in the University of North Carolina EoE Registry. Patients were categorized with histologically active (≥ 15 eosinophils per high-power field [eos/hpf]) or inactive (< 15 eos/hpf) disease. Dysphagia severity was measured with a Likert scale. QoL was measured with 36-Item Short Form (SF-36), compared between active and inactive groups, and assessed longitudinally. RESULTS: Of 147 EoE cases, those with inactive disease (n = 56) reported less dysphagia severity (3.2 vs. 1.9; p = 0.003) and had lower endoscopic severity (3.8 vs. 1.0; p < 0.001) than those with active disease (n = 91). While SF-36 scores did not differ between active and inactive status, lower mental component scores (MCS) were seen in patients treated with empiric dietary elimination (44.9 vs. 50.8; p = 0.005). Dysphagia severity was negatively correlated with both physical component score (PCS) (r = -0.33; p < 0.001) and MCS (r = -0.18; p = 0.03). Despite more cases achieving histologic response over time, SF-36 scores did not improve on either raw or adjusted analyses. CONCLUSION: QoL measured by SF-36 in EoE was similar regardless of histologic disease activity and was in the range of population averages. General QoL metrics like the SF-36 do not appear to have substantial utility in EoE.


Assuntos
Transtornos de Deglutição/patologia , Esofagite Eosinofílica/patologia , Qualidade de Vida , Adulto , Esofagite Eosinofílica/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina , Estudos Prospectivos , Sistema de Registros , Adulto Jovem
12.
Int J Mol Sci ; 22(20)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34681650

RESUMO

Extracellular vesicles (EVs) are secreted from hADSCs in low concentrations, which makes it difficult to utilize them for the development of therapeutic products. To overcome the problem associated with low concentration, we proposed human lactoferrin (hLF) as a stimulant for the secretion of hADSC-derived EVs. hLF has been reported to upregulate intracellular Ca2+, which is known to be capable of increasing EV secretion. We cultured hADSCs in hLF-supplemented media and analyzed the changes in intracellular Ca2+ concentration. The characteristics of hADSC-derived EVs secreted by hLF stimulation were analyzed through their number, membrane protein markers, and the presence of hLFs to EVs. The function of hADSC-derived EVs was investigated through their effects on dermal fibroblasts. We found that hLF helped hADSCs effectively uptake Ca2+, resulting in an increase of EVs secretion by more than a factor of 4. The resulting EVs had enhanced proliferation and collagen synthesis effect on dermal fibroblasts when compared to the same number of hADSC-derived EVs secreted without hLF stimulation. The enhanced secretion of hADSC-derived EVs increased collagen synthesis through enhanced epidermal penetration, which resulted from increased EV numbers. In summary, we propose hLF to be a useful stimulant in increasing the secretion rate of hADSC-derived EVs.


Assuntos
Vesículas Extracelulares/metabolismo , Lactoferrina/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Modelos Biológicos , Tecido Adiposo/citologia , Adolescente , Cálcio/metabolismo , Técnicas de Cultura de Células , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Regulação para Cima/efeitos dos fármacos
13.
Dig Liver Dis ; 54(4): 477-482, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34789398

RESUMO

BACKGROUND: There are few data assessing treatment response in older eosinophilic esophagitis (EoE) patients and we evaluated treatment outcomes to topical corticosteroids (tCS) in this older population. METHODS: This retrospective cohort study of the UNC EoE Clinicopathologic database included subjects with a new diagnosis of EoE treated with tCS. Histologic responses, global symptom response, and endoscopic changes were recorded. Older EoE patients (≥65 years) were compared to younger EoE patients (<65). RESULTS: We identified 467 EoE patients treated with tCS, 12 (3%) of whom were ≥65 years. Compared to those <65 years, patients ≥65 had longer symptom duration and worse endoscopy scores, but most clinical features were similar. Post-treatment peak eosinophil counts trended higher in the <65 group (25.0 vs 5.5; p = 0.07). Histological response was greater in the ≥65 population at <15 eos/hpf (92% vs 57%; p = 0.02), ≤6 eos/hpf (83% vs 50%; p = 0.02), and <1 eos/hpf (58% vs 29%; p = 0.03). Older age was independently associated with increased odds of histologic response (adjusted OR 8.48, 95% CI: 1.08-66.4). CONCLUSIONS: EoE patients ≥65 years had a higher likelihood of responding to tCS therapy, suggesting they should be studied more closely and included in future trials.


Assuntos
Esofagite Eosinofílica , Idoso , Esofagite Eosinofílica/diagnóstico , Eosinófilos , Glucocorticoides/uso terapêutico , Humanos , Estudos Retrospectivos , Esteroides/uso terapêutico
14.
Clin Res Hepatol Gastroenterol ; 45(5): 101746, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34182183

RESUMO

BACKGROUND: Gastric and duodenal mucosa may appear normal in eosinophilic gastroenteritis (EGE). Adult gastroenterologists typically biopsy only in the setting of mucosal abnormalities or symptoms, while pediatric providers biopsy all patients. The biopsy yield of EGE has not been adequately evaluated. AIMS: To evaluate the biopsy yield of EGE in a pediatric cohort and assess predictors of increased biopsy yield. METHODS: We identified patients age 0-18 who underwent upper endoscopy. We recorded endoscopic findings, pathology, demographics, and clinical and laboratory characteristics. We identified EGE cases (>20 eosinophils per high-power field on stomach and/or duodenum biopsy). We compared characteristics between EGE and non-EGE cases, calculated biopsy diagnostic yield, and performed multivariate analysis for predictors of increased biopsy yield. RESULTS: In 509 patients (55.6% female, mean age 10.3 years, 69.7% white, 58.7% atopic), biopsy diagnostic yield for EGE was 1.2% (6/509) among all subjects, 7.7% (3/39) for those with peripheral eosinophilia (≥500 eos/uL), 9.1% (3/33) for those with hypoalbuminemia (<3.5 g/dL), and 25.0% (3/12) for those with peripheral eosinophilia and hypoalbuminemia. The odds of EGE were 27.8 (95% CI 3.3-231.8) times greater among those with peripheral eosinophilia. The mean total biopsy surface area and number of fragments was similar between patients with and without EGE. The area under the ROC curve for blood eosinophil counts and albumin level for predicting EGE was 0.926. CONCLUSIONS: The biopsy diagnostic yield for EGE is low but increases with peripheral eosinophilia and hypoalbuminemia. Patients with these features should have biopsies obtained, regardless of endoscopic appearance.


Assuntos
Enterite , Eosinofilia , Hipoalbuminemia , Doenças Metabólicas , Adolescente , Adulto , Biópsia , Criança , Pré-Escolar , Enterite/diagnóstico , Eosinofilia/diagnóstico , Feminino , Gastrite , Gastroscopia , Humanos , Hipoalbuminemia/diagnóstico , Lactente , Recém-Nascido , Masculino
15.
J Exp Zool A Ecol Genet Physiol ; 321(8): 457-66, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25045088

RESUMO

The myo-inositol biosynthesis (MIB) pathway converts glucose-6-phosphate to the compatible osmolyte myo-inositol, which protects cells from salinity stress. We exposed tilapia larvae just after yolk sac resorption to various hypersaline environments and recorded robust induction of the enzymes that constitute the MIB pathway, myo-inositol-phosphate synthase (MIPS), and inositol monophosphatase 1 (IMPA1). Strong up-regulation of these enzymes is evident at both mRNA (quantitative real-time PCR) and protein (densitometric analysis of Western blots) levels. The highest level of induction of these enzymes occurs at the highest salinity that larvae were exposed to (90 ppt). Less severe salinity stress causes a proportionately reduced induction of the MIB pathway. Two distinct MIPS mRNA variants are present in tilapia larvae and both are induced at comparable levels for all the salinity challenges tested (34, 70, and 90 ppt). Immunohistochemical localization of IMPA1 protein in sagittal sections of salinity stressed and control larvae identified tissues that are particularly potent in inducing the MIB pathway. These tissues include the skin (epidermis), gills, eye (ciliary epithelium) and heart. In particular, the epidermis directly facing the external milieu showed a very strong induction of IMPA1 immunoreactivity. IMPA1 induction in response to salinity stress was not observed in other tissues suggesting that tilapia larvae may also utilize compatible organic osmolytes other than solely myo-inositol for osmoprotection. We conclude that the MIB pathway plays an important role in protecting multiple (but not all) tissues of tilapia larvae from hyperosmotic salinity stress.


Assuntos
Inositol/biossíntese , Tilápia/fisiologia , Animais , Epitélio/fisiologia , Olho/metabolismo , Brânquias/fisiologia , Coração/fisiologia , Larva/fisiologia , Mio-Inositol-1-Fosfato Sintase/metabolismo , Osmorregulação , Monoéster Fosfórico Hidrolases/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Salinidade
16.
Regen Med ; 6(6): 689-99, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22050521

RESUMO

AIMS: Dental tissue has been the focus of attention as an easily accessible postnatal tissue source of high-quality stem cells. Since the first report on the dental pulp stem cells (DPSCs) from permanent third molar teeth, stem cells from human exfoliated deciduous teeth (SHED) were identified as a population distinct from DPSCs. In this study, we compared DPSCs from supernumerary teeth and SHED in three age- and sex-matched patients. PATIENTS & METHODS: Dental samples were obtained from the three patients, who were 6 years old and male, with the parental consent of the three donors, and then isolated cells from dental pulp for comparative analysis between supernumerary DPSCs and SHED. RESULTS: Colony-forming unit fibroblast levels and the proliferation rate of supernumerary DPSCs were slightly lower than that of SHED. The expression of cell surface antigens in supernumerary DPSCs and SHED were almost identical. Cells were mainly expressing endogenous mesodermal and ectodermal lineage markers. Differentiation capacity to osteogenic, adipogenic and chondrogenic lineage was similar in the SHED and supernumerary DPSCs. Migration assay revealed that both supernumerary DPSCs and SHED rapidly migrated toward wounded areas. Supernumerary DPSCs were altered in cell growth after storage for 2 years. Specially, the population doubling time of supernumerary DPSCs increased while that of SHED remained nearly unchanged. CONCLUSION: Both supernumerary teeth and deciduous teeth share many characteristics, such as highly proliferative clonogenic cells with a similar immunophenotype to that of mesenchymal stem cells, although they are inferior to SHED for long-term banking. Our findings suggest that supernumerary teeth are also easily accessible and noninvasive sources of postnatal stem cells with multipotency and regenerative capacity.


Assuntos
Células-Tronco Mesenquimais/citologia , Esfoliação de Dente/patologia , Dente Decíduo/patologia , Dente Supranumerário/patologia , Diferenciação Celular , Proliferação de Células , Separação Celular , Células Cultivadas , Criança , Células Clonais , Análise Citogenética , Polpa Dentária/citologia , Humanos , Imunofenotipagem , Incisivo/citologia , Masculino , Cicatrização
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