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1.
N Engl J Med ; 390(24): 2252-2263, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38924732

RESUMEN

BACKGROUND: Benralizumab is an eosinophil-depleting anti-interleukin-5 receptor α monoclonal antibody. The efficacy and safety of benralizumab in patients with eosinophilic esophagitis are unclear. METHODS: In a phase 3, multicenter, double-blind, randomized, placebo-controlled trial, we assigned patients 12 to 65 years of age with symptomatic and histologically active eosinophilic esophagitis in a 1:1 ratio to receive subcutaneous benralizumab (30 mg) or placebo every 4 weeks. The two primary efficacy end points were histologic response (≤6 eosinophils per high-power field) and the change from baseline in the score on the Dysphagia Symptom Questionnaire (DSQ; range, 0 to 84, with higher scores indicating more frequent or severe dysphagia) at week 24. RESULTS: A total of 211 patients underwent randomization: 104 were assigned to receive benralizumab, and 107 were assigned to receive placebo. At week 24, more patients had a histologic response with benralizumab than with placebo (87.4% vs. 6.5%; difference, 80.8 percentage points; 95% confidence interval [CI], 72.9 to 88.8; P<0.001). However, the change from baseline in the DSQ score did not differ significantly between the two groups (difference in least-squares means, 3.0 points; 95% CI, -1.4 to 7.4; P = 0.18). There was no substantial between-group difference in the change from baseline in the Eosinophilic Esophagitis Endoscopic Reference Score, which reflects endoscopic abnormalities. Adverse events were reported in 64.1% of the patients in the benralizumab group and in 61.7% of those in the placebo group. No patients discontinued the trial because of adverse events. CONCLUSIONS: In this trial involving patients 12 to 65 years of age with eosinophilic esophagitis, a histologic response (≤6 eosinophils per high-power field) occurred in significantly more patients in the benralizumab group than in the placebo group. However, treatment with benralizumab did not result in fewer or less severe dysphagia symptoms than placebo. (Funded by AstraZeneca; MESSINA ClinicalTrials.gov number, NCT04543409.).


Asunto(s)
Anticuerpos Monoclonales Humanizados , Esofagitis Eosinofílica , Eosinófilos , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Trastornos de Deglución/etiología , Trastornos de Deglución/tratamiento farmacológico , Método Doble Ciego , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/inmunología , Subunidad alfa del Receptor de Interleucina-5/antagonistas & inhibidores , Recuento de Leucocitos
2.
N Engl J Med ; 387(25): 2317-2330, 2022 12 22.
Artículo en Inglés | MEDLINE | ID: mdl-36546624

RESUMEN

BACKGROUND: Dupilumab, a fully human monoclonal antibody, blocks interleukin-4 and interleukin-13 signaling, which have key roles in eosinophilic esophagitis. METHODS: We conducted a three-part, phase 3 trial in which patients 12 years of age or older underwent randomization in a 1:1 ratio to receive subcutaneous dupilumab at a weekly dose of 300 mg or placebo (Part A) or in a 1:1:1 ratio to receive 300 mg of dupilumab either weekly or every 2 weeks or weekly placebo (Part B) up to week 24. Eligible patients who completed Part A or Part B continued the trial in Part C, in which those who completed Part A received dupilumab at a weekly dose of 300 mg up to week 52 (the Part A-C group); Part C that included the eligible patients from Part B is ongoing. The two primary end points at week 24 were histologic remission (≤6 eosinophils per high-power field) and the change from baseline in the Dysphagia Symptom Questionnaire (DSQ) score (range, 0 to 84, with higher values indicating more frequent or more severe dysphagia). RESULTS: In Part A, histologic remission occurred in 25 of 42 patients (60%) who received weekly dupilumab and in 2 of 39 patients (5%) who received placebo (difference, 55 percentage points; 95% confidence interval [CI], 40 to 71; P<0.001). In Part B, histologic remission occurred in 47 of 80 patients (59%) with weekly dupilumab, in 49 of 81 patients (60%) with dupilumab every 2 weeks, and in 5 of 79 patients (6%) with placebo (difference between weekly dupilumab and placebo, 54 percentage points; 95% CI, 41 to 66 [P<0.001]; difference between dupilumab every 2 weeks and placebo, 56 percentage points; 95% CI, 43 to 69 [not significant per hierarchical testing]). The mean (±SD) DSQ scores at baseline were 33.6±12.41 in Part A and 36.7±11.22 in Part B; the scores improved with weekly dupilumab as compared with placebo, with differences of -12.32 (95% CI, -19.11 to -5.54) in Part A and -9.92 (95% CI, -14.81 to -5.02) in Part B (both P<0.001) but not with dupilumab every 2 weeks (difference in Part B, -0.51; 95% CI, -5.42 to 4.41). Serious adverse events occurred in 9 patients during the Part A or B treatment period (in 7 who received weekly dupilumab, 1 who received dupilumab every 2 weeks, and 1 who received placebo) and in 1 patient in the Part A-C group during the Part C treatment period who received placebo in Part A and weekly dupilumab in Part C. CONCLUSIONS: Among patients with eosinophilic esophagitis, subcutaneous dupilumab administered weekly improved histologic outcomes and alleviated symptoms of the disease. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03633617.).


Asunto(s)
Anticuerpos Monoclonales Humanizados , Trastornos de Deglución , Esofagitis Eosinofílica , Adolescente , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Trastornos de Deglución/tratamiento farmacológico , Trastornos de Deglución/etiología , Trastornos de Deglución/patología , Método Doble Ciego , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/tratamiento farmacológico , Esofagitis Eosinofílica/patología , Inyecciones Subcutáneas , Resultado del Tratamiento , Niño , Adulto Joven
3.
Gut ; 73(3): 398-406, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38050037

RESUMEN

OBJECTIVE: To assess the effect of long-term dupilumab on histological, symptomatic and endoscopic aspects of eosinophilic oesophagitis (EoE) in adolescent and adult patients with and without prior use of swallowed topical corticosteroids (STC) or prior inadequate response, intolerance or contraindication to STC. DESIGN: Pre-specified analysis of data from the phase 3 LIBERTY EoE TREET study on patients who received dupilumab 300 mg once a week or placebo for 24 weeks (W24) in parts A and B, and an additional 28 weeks (W52) in part C. Patients were categorised as with/without prior STC use and with/without inadequate/intolerance/contraindication to STC. The proportion of patients achieving ≤6 eosinophils per high-power field (eos/hpf), absolute change in Dysphagia Symptom Questionnaire (DSQ) score, mean change in Endoscopic Reference Score and Histologic Scoring System grade/stage scores were assessed for each subgroup. RESULTS: Regardless of prior STC use, dupilumab increased the proportion of patients achieving ≤6 eos/hpf and improved DSQ score versus placebo at W24, with improvements maintained or improved at W52. The DSQ score and the proportion of patients achieving ≤6 eos/hpf after switching from placebo to dupilumab at W24 were similar to those observed in the dupilumab group at W24, regardless of prior STC use or inadequate/intolerance/contraindication to STC. Improvements in other outcomes with dupilumab were similar in patients with/without prior STC use or inadequate/intolerance/contraindication to STC. CONCLUSION: Dupilumab 300 mg once a week demonstrated efficacy and was well tolerated in patients with EoE regardless of prior STC use or inadequate response, intolerance and/or contraindication to STC. TRIAL REGISTRATION NUMBER: NCT03633617.


Asunto(s)
Trastornos de Deglución , Esofagitis Eosinofílica , Adolescente , Adulto , Humanos , Anticuerpos Monoclonales Humanizados/efectos adversos , Trastornos de Deglución/etiología , Trastornos de Deglución/tratamiento farmacológico , Método Doble Ciego , Endoscopía , Esofagitis Eosinofílica/tratamiento farmacológico , Glucocorticoides/uso terapéutico , Resultado del Tratamiento
4.
Am J Physiol Gastrointest Liver Physiol ; 327(1): G105-G116, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38772905

RESUMEN

The neural connectivity among the oral cavity, pharynx, and esophagus is a critical component of infant feeding physiology. Central integration of oral and pharyngeal afferents alters motor outputs to structures that power swallowing, but the potential effects of esophageal afferents on preesophageal feeding physiology are unclear. These effects may explain the prevalence of oropharyngeal dysphagia in infants suffering from gastroesophageal reflux (GER), though the mechanism underlying this relationship remains unknown. Here we use the validated infant pig model to assess the impacts of simulated GER on preesophageal feeding parameters. We used high-speed videofluoroscopy and electromyography to record bottle-feeding before and following the infusion of a capsaicin-containing solution into the lower esophagus. Sucking parameters were minimally affected by capsaicin exposure, such that genioglossus activity was unchanged and tongue kinematics were largely unaffected. Aspects of the pharyngeal swallow were altered with simulated GER, including increased thyrohyoid muscle activity, increased excursions of the hyoid and thyroid per swallow, decreased swallow frequency, and increased bolus sizes. These results suggest that esophageal afferents can elicit changes in pharyngeal swallowing. In addition, decreased swallowing frequency may be the mechanism by which esophageal pathologies induce oropharyngeal dysphagia. Although recent work indicates that oral or pharyngeal capsaicin may improve dysphagia symptoms, the decreased performance following esophageal capsaicin exposure highlights the importance of designing sensory interventions based upon neurophysiology and the mechanisms underlying disordered feeding. This mechanistic approach requires comprehensive data collection across the entirety of the feeding process, which can be achieved using models such as the infant pig.NEW & NOTEWORTHY Simulated gastroesophageal reflux (GER) in an infant pig model resulted in significant changes in pharyngeal swallowing, which suggests that esophageal afferents are centrally integrated to alter motor outputs to the pharynx. In addition, decreased swallow frequency and increased bolus sizes may be underlying mechanisms by which esophageal pathologies induce oropharyngeal dysphagia. The infant pig model used here allows for a mechanistic approach, which can facilitate the design of intervention strategies based on neurophysiology.


Asunto(s)
Capsaicina , Deglución , Reflujo Gastroesofágico , Animales , Reflujo Gastroesofágico/fisiopatología , Porcinos , Deglución/efectos de los fármacos , Capsaicina/farmacología , Esófago/fisiopatología , Esófago/efectos de los fármacos , Esófago/inervación , Electromiografía , Faringe/fisiopatología , Animales Recién Nacidos , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/etiología , Orofaringe/fisiopatología , Alimentación con Biberón , Femenino , Fluoroscopía
5.
Am J Gastroenterol ; 119(2): 262-269, 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-37782465

RESUMEN

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.


Asunto(s)
Trastornos de Deglución , Enteritis , Eosinofilia , Esofagitis Eosinofílica , Gastritis , Humanos , Esofagitis Eosinofílica/diagnóstico , Trastornos de Deglución/etiología , Estudios Retrospectivos , Minorías Étnicas y Raciales , Esteroides/uso terapéutico , Glucocorticoides/uso terapéutico
6.
Am J Gastroenterol ; 119(10): 2002-2009, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-38661151

RESUMEN

INTRODUCTION: There are limited longitudinal data on the impact of chronic therapy on the natural history of eosinophilic esophagitis (EoE), a chronic allergic disease of the esophagus. The purpose of this study was to evaluate if patients with well-controlled EoE were less likely to develop fibrostenotic complications. METHODS: Subjects were identified from a database of pediatric patients with EoE at the Children's Hospital of Philadelphia started in 2000. Patients were then searched in adult medical records to identify patients who transitioned care. All office visits, emergency department visits, and endoscopic, histologic, and imaging reports were reviewed for the primary outcome of strictures and the secondary outcomes of food impactions and dysphagia. Cox proportional hazard regression was performed for outcomes. RESULTS: One hundred five patients were identified with the mean follow-up of 11.4 ± 4.9 years. 52.3% (n = 55) had a period of histologic disease control defined as ≥2 consecutive endoscopies with histologic remission. These patients were less likely to develop strictures compared with patients who did not have a period of histologic control (HR 0.232; 95% CI 0.084-0.64, P = 0.005). Patients who were diagnosed at younger ages were less likely to develop strictures. Presentation with dysphagia or impaction was associated with higher rate of stricture development. DISCUSSION: In this cohort study with > 10 years of follow-up, children with EoE with a period of histologic disease control and diagnosed at younger ages were less likely to develop esophageal strictures. While this suggests histologic remission is associated with reduction of remodeling complications, additional prospective data with long-term follow-up are needed.


Asunto(s)
Esofagitis Eosinofílica , Eosinófilos , Estenosis Esofágica , Humanos , Esofagitis Eosinofílica/complicaciones , Esofagitis Eosinofílica/patología , Esofagitis Eosinofílica/diagnóstico , Masculino , Estenosis Esofágica/etiología , Femenino , Niño , Adolescente , Preescolar , Recuento de Leucocitos , Trastornos de Deglución/etiología , Estudios Retrospectivos , Estudios de Seguimiento , Modelos de Riesgos Proporcionales , Esofagoscopía
7.
Am J Gastroenterol ; 119(10S Suppl): S2185, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39446592

RESUMEN

INTRODUCTION: Lymphocytic esophagitis (LyE) is a rare esophageal disorder of unknown etiology, characterized by dense peripapillary lymphocytes without neutrophils or eosinophils, and spongiosis. Patients typically present with symptoms such as dysphagia or chest pain. Here, we describe a notable case of lymphocytic esophagitis in a patient who presented with food impaction. CASE DESCRIPTION/METHODS: A 53-year-old woman with a history of pityriasis lichenoideschronica and rheumatoid arthritis reported chronic dysphagia and sought emergency care for food impaction. A subsequent upper endoscopy revealed a long submucosal tear in the upper esophagus during intubation (see Figure 1A), leading to the procedure's cessation. A follow-up upper endoscopy 9 weeks later, employing an ultra-slim scope, identified severe stenosis in the upper esophagus (see Figure 1B). Dilation was performed using a Savary dilator. Examination of the esophageal lining revealed edema, rings, and furrows. Proximal and distal esophageal biopsies were obtained, indicating a marked increase in intraepithelial lymphocytes, with an absence of eosinophils or neutrophils. The squamous epithelium exhibited evidence of spongiosis and necrotic keratinocytes, consistent with a diagnosis of lymphocytic esophagitis. The patient continued omeprazole 40 mg twice daily and started budesonide at 1 mg twice daily. A repeat upper endoscopy with esophageal biopsies demonstrated a significant improvement in lymphocytic infiltration (see Figure 2A-B). DISCUSSION: LyE typically manifests in females during their 5th-6th decades, presenting a notable contrast to eosinophilic esophagitis (EOE), which predominantly affects males in their 2nd-3rd decades. However, the endoscopic appearance of LyE often mirrors that of EOE. Studies suggest potential associations between LyE and Crohn's disease in children, as well as primary esophageal dysmotility in adults. Notably, our patient has a history of rheumatoid arthritis, a correlation observed in 2 other cases in the literature. While limited literature exists on pityriasis lichenoideschronica with esophageal involvement, specifically presenting as LyE, this singular case underscores the interconnection of these 2 disease processes. These observations raise the possibility of an autoimmune etiology. There is no consensus on the lymphocyte count threshold for diagnosis, a challenge compounded by the rarity of the disease, leading to a lack of definitive guidelines for optimal management.JOURNAL/ajgast/04.03/00000434-202410001-03261/figure1/v/2024-10-11T031912Z/r/image-tiff.


Asunto(s)
Artritis Reumatoide , Esofagitis , Pitiriasis Liquenoide , Humanos , Femenino , Persona de Mediana Edad , Artritis Reumatoide/complicaciones , Pitiriasis Liquenoide/patología , Pitiriasis Liquenoide/diagnóstico , Pitiriasis Liquenoide/complicaciones , Esofagitis/patología , Esofagitis/diagnóstico , Esofagitis/complicaciones , Esofagoscopía , Linfocitos/patología , Trastornos de Deglución/etiología
8.
Am J Gastroenterol ; 119(6): 1066-1073, 2024 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-38299582

RESUMEN

INTRODUCTION: Eosinophilic esophagitis (EoE) is associated with atopy; however, recent studies have identified an association with food-specific immunoglobulin G 4 (FS-IgG 4 ) rather than immunoglobulin E antibodies. This study aimed to evaluate the role of serum FS-IgG 4 in guiding an elimination diet and its outcomes. METHODS: Patients with and without EoE were enrolled in a prospective, controlled, single tertiary center trial. Serum FS-IgG 4 titers, esophageal eosinophil counts, and dysphagia symptom questionnaire scores were assessed, and participants with elevated FS-IgG 4 (ImmunoCAP, cutoff of 10 mgA/L) commenced 6-week targeted elimination diet. Repeat serum FS-IgG 4 and endoscopic and histologic examination were performed at 6-week follow-up. RESULTS: Twenty-two patients with active EoE and 13 controls were recruited. Serum FS-IgG 4 to milk, wheat, soy, eggs, and nuts was significantly higher in EoE ( P = 0.0002, P = 0.002, P = 0.003, P = 0.012, and P < 0.001, respectively). Elevated serum FS-IgG 4 to 1 or more food groups (median 2) was identified in 21/22 (95.4%) patients with EoE; 20/21 underwent 6-week dietary elimination. Median reductions in dysphagia symptom questionnaire score and EoE endoscopic reference score after elimination were 8 ( P = 0.0007) and 1 ( P = 0.002), respectively. Nine (45%) patients had histological remission (<15 eosinophils per high-power field). Fall in median esophageal eosinophil count was not statistically significant (50 vs 23; P = 0.068). Serum FS-IgG 4 did not decline by 6-week follow-up. DISCUSSION: Serum FS-IgG 4 to milk, wheat, soy, egg, and nuts was present at higher levels in EoE, with targeted elimination resulting in 45% histologic remission rate. Serum FS-IgG 4 has potential as a noninvasive biomarker in EoE. When successful, FS-IgG 4 -led elimination diet can negate need for medications and be viewed more favorably by patients because of its smaller endoscopic burden compared with empirical elimination diets.


Asunto(s)
Esofagitis Eosinofílica , Inmunoglobulina G , Humanos , Esofagitis Eosinofílica/dietoterapia , Esofagitis Eosinofílica/inmunología , Esofagitis Eosinofílica/sangre , Femenino , Masculino , Inmunoglobulina G/sangre , Adulto , Estudios Prospectivos , Persona de Mediana Edad , Hipersensibilidad a los Alimentos/dietoterapia , Hipersensibilidad a los Alimentos/complicaciones , Hipersensibilidad a los Alimentos/inmunología , Hipersensibilidad a los Alimentos/sangre , Trastornos de Deglución/etiología , Trastornos de Deglución/dietoterapia , Esofagoscopía , Eosinófilos/inmunología , Adulto Joven , Dieta de Eliminación
9.
Curr Opin Oncol ; 36(3): 128-135, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573201

RESUMEN

PURPOSE OF REVIEW: Recent recommendations on cachexia highlight, in head and neck cancers, the heterogeneity of studies, focusing on weight loss and sequelae including swallowing disorders. The current national guidelines emphasize that, in cases of concurrent chemoradiotherapy (cCRT) involving the oral cavity and oropharynx, prophylactic gastrostomy placement should be carried out systematically. We review why this technique is particularly relevant in this specific location for the feasibility of cCRT. RECENT FINDINGS: A randomized trial is underway on swallowing disorders and the quality of life of patients after prophylactic vs. reactive gastrostomy in advanced oropharyngeal cancer patients treated with CRT. Concurrently, recent literature reviews emphasize the importance of the cumulative dose of chemotherapy for local control and survival. In cases of cCRT involving the oral cavity or the oropharynx, nutritional support could have a beneficial or detrimental impact on chemotherapy. SUMMARY: Specifically for patients treated with cCRT involving the oral cavity and oropharynx, prophylactic gastrostomy would be able to fulfill the three objectives of local control, survival, and quality of life, minimizing complications related to nutritional support. Studies need to be more homogeneous. In clinical practice, nutrition should primarily assist in carrying out cancer treatment when survival is the main goal.


Asunto(s)
Trastornos de Deglución , Neoplasias de Cabeza y Cuello , Humanos , Quimioradioterapia , Trastornos de Deglución/etiología , Trastornos de Deglución/prevención & control , Gastrostomía , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Boca , Orofaringe , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto
10.
Mol Genet Metab ; 142(3): 108510, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38843620

RESUMEN

BACKGROUND: Information about dysarthria and dysphagia in mitochondrial diseases (MD) is scarce. However, this knowledge is needed to identify speech and swallowing problems early, to monitor the disease course, and to develop and offer optimal treatment and support. This study therefore aims to examine the prevalence and severity of dysarthria and dysphagia in patients with MD and its relation to clinical phenotype and disease severity. Secondary aim is to determine clinically relevant outcome measures for natural history studies and clinical trials. METHODS: This retrospective cross-sectional medical record study includes adults (age ≥ 18 years) diagnosed with genetically confirmed MD who participated in a multidisciplinary admission within the Radboud center for mitochondrial medicine between January 2015 and April 2023. Dysarthria and dysphagia were examined by administering the Radboud dysarthria assessment, swallowing speed, dysphagia limit, test of mastication and swallowing solids (TOMASS), and 6-min mastication test (6MMT). The disease severity was assessed using the Newcastle mitochondrial disease scale for adults (NMDAS). RESULTS: The study included 224 patients with MD with a median age of 42 years of whom 37.5% were male. The pooled prevalence of dysarthria was 33.8% and of dysphagia 35%. Patients with MD showed a negative deviation from the norm on swallowing speed, TOMASS (total time) and the 6MMT. Furthermore, a significant moderate relation was found between the presence of dysarthria and the clinical phenotypes. There was a statistically significant difference in total time on the TOMASS between the clinical phenotypes. Finally, disease severity showed a significant moderate relation with the severity of dysarthria and a significant weak relation with the severity of dysphagia. CONCLUSION: Dysarthria and dysphagia occur in about one-third of patients with MD. It is important for treating physicians to pay attention to this subject because of the influence of both disorders on social participation and wellbeing. Referral to a speech and language therapist should therefore be considered, especially in patients with a more severe clinical phenotype. The swallowing speed, TOMASS and 6MMT are the most clinically relevant tests to administer.


Asunto(s)
Trastornos de Deglución , Disartria , Enfermedades Mitocondriales , Humanos , Trastornos de Deglución/etiología , Trastornos de Deglución/fisiopatología , Disartria/etiología , Disartria/fisiopatología , Masculino , Femenino , Enfermedades Mitocondriales/complicaciones , Enfermedades Mitocondriales/fisiopatología , Adulto , Persona de Mediana Edad , Estudios Retrospectivos , Estudios Transversales , Anciano , Índice de Severidad de la Enfermedad , Prevalencia , Deglución , Adulto Joven , Fenotipo
11.
BMC Cancer ; 24(1): 1109, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237888

RESUMEN

Meaningful engagement with stakeholders in research demands intentional approaches. This paper describes the development of a framework to guide stakeholder engagement as research partners in a pragmatic trial proposed to evaluate behavioral interventions for dysphagia in head and neck cancer patients. We highlight the core principles of stakeholder engagement including representation of all perspectives, meaningful participation, respectful partnership with stakeholders, and accountability to stakeholders; and describe how these principles were operationalized to engage relevant stakeholders throughout the course of a large clinical trial.


Asunto(s)
Neoplasias de Cabeza y Cuello , Participación de los Interesados , Humanos , Neoplasias de Cabeza y Cuello/terapia , Trastornos de Deglución/terapia , Trastornos de Deglución/etiología , Proyectos de Investigación , Ensayos Clínicos Pragmáticos como Asunto/métodos , Participación del Paciente
12.
BMC Cancer ; 24(1): 896, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-39060966

RESUMEN

OBJECTIVE: Dysphagia is common in individuals who have undergone posterior fossa tumor (PFT) resection and negatively impacts on the individual's quality of life, nutritional status, and overall health. We aimed to quantitatively synthesize data from studies of the prevalence of dysphagia following PFT resection. METHODS: PubMed, Web of Science, the Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), Wanfang database, and VIP database were searched for case-control and cross-sectional studies that evaluated the prevalence of dysphagia after PFT surgery. Meta-analyses were performed to determine the prevalence of dysphagia. Subgroup and meta-regression analyses were performed to determine the sources of heterogeneity among the studies. RESULTS: A total of 22 studies were included, involving 20,921 cases. A meta-analysis of the random-effects model showed that the pooled global prevalence of dysphagia following PFT resection was 21.7% (95% confidence interval: 16.9-26.6). The subgroup and meta-regression analyses demonstrated that participant age (P < 0.001), assessment methods (P = 0.004), and geographical region of the study participants (P = 0.001) were sources of heterogeneity among the studies. CONCLUSIONS: Dysphagia has a high prevalence following PFT resection. Individuals with PFTs who are at a high risk for dysphagia should be identified early through screening. Multidisciplinary diagnosis and treatment of dysphagia are required to improve the outcomes in the early stages after PFT resection.


Asunto(s)
Trastornos de Deglución , Neoplasias Infratentoriales , Complicaciones Posoperatorias , Humanos , Trastornos de Deglución/etiología , Trastornos de Deglución/epidemiología , Prevalencia , Neoplasias Infratentoriales/cirugía , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Calidad de Vida
13.
BMC Cancer ; 24(1): 648, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802747

RESUMEN

BACKGROUND: This study aimed to assess the long-term effect of level IIb clinical target volume (CTV) optimisation on survival, xerostomia, and dysphagia in patients with nasopharyngeal carcinoma (NPC). METHODS: Clinical data of 415 patients with NPC treated with intensity-modulated radiotherapy between December 2014 and October 2018 were retrospectively analysed. The patients were categorised into modified and comparison groups. Late xerostomia and dysphagia were evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer scoring. Survival analysis was performed using the Kaplan-Meier method. Differences in late toxicity and dose parameters between both groups were compared. Prognostic factors for survival and late toxicity were assessed using regression analyses. RESULTS: Patients in the modified group developed late xerostomia and dysphagia less frequently than those in the comparison group did (P < 0.001). The mean dose (Dmean) and V26 of parotid glands; Dmean and V39 of submandibular glands; and Dmean of sublingual glands, oral cavity, larynx, and superior, middle, and lower pharyngeal constrictor muscles were lower in the modified group than those in the comparison group (all P < 0.001). Both groups had no significant differences in overall, local recurrence-free, distant metastasis-free, or progression-free survival. The Dmean of the parotid and sublingual glands was a risk factor for xerostomia. The Dmean of the parotid and sublingual glands and middle pharyngeal constrictor muscle was a risk factor for dysphagia. CONCLUSIONS: Level IIb optimisation in NPC patients who meet certain criteria specially the exclusion of positive retropharyngeal nodes treated with intensity-modulated radiotherapy has the potential to better protect the salivary and swallowing structures, decreasing the development of late radiation-induced xerostomia and dysphagia while maintaining long-term survival.


Asunto(s)
Trastornos de Deglución , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidad Modulada , Xerostomía , Humanos , Trastornos de Deglución/etiología , Masculino , Xerostomía/etiología , Femenino , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicaciones , Carcinoma Nasofaríngeo/patología , Persona de Mediana Edad , Radioterapia de Intensidad Modulada/efectos adversos , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Estudios de Seguimiento , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/complicaciones , Adulto , Anciano , Traumatismos por Radiación/etiología , Traumatismos por Radiación/prevención & control , Deglución , Glándulas Salivales/efectos de la radiación , Glándulas Salivales/patología , Glándulas Salivales/diagnóstico por imagen , Dosificación Radioterapéutica , Pronóstico , Adulto Joven
14.
Am J Med Genet A ; 194(8): e63634, 2024 08.
Artículo en Inglés | MEDLINE | ID: mdl-38619072

RESUMEN

Feeding difficulties, aspiration, and failure to thrive in infancy are commonly seen in patients with Prader-Willi Syndrome (PWS) and attributed to hypotonia. Patients with PWS and laryngeal clefts were identified by review of medical records at three tertiary care children's hospitals between 2017 and 2022. We present three patients with PWS with feeding difficulties who were also found to have laryngeal clefts which likely contributed to their feeding difficulties. Additional factors such as airway anomalies should be considered in patients with PWS, especially when swallowing dysfunction, dysphagia, or abnormal swallow evaluations are present.


Asunto(s)
Laringe , Hipotonía Muscular , Síndrome de Prader-Willi , Humanos , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/diagnóstico , Síndrome de Prader-Willi/genética , Síndrome de Prader-Willi/patología , Hipotonía Muscular/genética , Hipotonía Muscular/patología , Femenino , Masculino , Lactante , Laringe/anomalías , Laringe/patología , Laringe/fisiopatología , Preescolar , Trastornos de Deglución/etiología , Trastornos de Deglución/diagnóstico , Anomalías Congénitas
15.
Epilepsia ; 65(5): 1374-1382, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38456606

RESUMEN

OBJECTIVE: Seizures can cause transient neurological symptoms, such as hemiparesis and aphasia. However, temporary swallowing changes leading to postictal dysphagia have not been previously described. Therefore, this study evaluated the presence of swallowing disorders following seizure. In addition, dysphagia severity and duration of any recovery from dysphagic symptoms were investigated. METHODS: The local clinical database of all fiberoptic endoscopic evaluation of swallowing (FEES) examinations performed from 2008 to 2019 was screened for patients diagnosed with seizures, but excluding patients with intensive care unit admission or intubation >24 h. Patient charts were evaluated to identify preexisting dysphagia or potential concurrent medical causes for dysphagia, including hyponatremia, increased intracranial pressure, sepsis, or other encephalopathies associated with infections, or other possible causes at the time of admission. Patients receiving >.5 defined daily doses of benzodiazepines or neuroleptics were also excluded. Age, sex, seizure semiology and etiology, comorbidities, concurrent pneumonia, and dysphagia course during hospitalization were evaluated as predictors of the occurrence of dysphagia or its potential duration. RESULTS: We identified 41 patients with dysphagia following a seizure, without evidence of any concurrent cause of swallowing dysfunction. These patients all presented with focal structural epilepsy, they had a mean age of 79 ± 11.3 years (range = 44-95 years), and 21 were women. The mean Elixhauser Comorbidity Score was 4.8. Hospital-acquired pneumonia was detected in 21 patients (51.2%). FEES diagnosed mild and severe dysphagia in 21 (51.2%) and 20 (48.8%) patients, respectively. Dysphagia improved significantly (p = .001) during hospitalization, persisting for an average of 3.9 days (median = 3 days, SD = 2.07 days, range = 1-8 days). SIGNIFICANCE: Dysphagia is a potential transient neurological deficit following seizure. Our findings suggest that older patients, with focal structural epilepsy, are at risk for postictal dysphagia. Further studies are needed to ascertain the prevalence, complications, and predictors of postictal dysphagia. Dysphagia screening may improve early detection in patients with relevant risk factors, as well as reduce the occurrence of aspiration pneumonia.


Asunto(s)
Trastornos de Deglución , Humanos , Trastornos de Deglución/epidemiología , Trastornos de Deglución/etiología , Trastornos de Deglución/diagnóstico , Femenino , Masculino , Anciano , Anciano de 80 o más Años , Persona de Mediana Edad , Adulto , Epilepsias Parciales/complicaciones , Convulsiones/complicaciones , Convulsiones/epidemiología , Convulsiones/diagnóstico , Estudios Retrospectivos
16.
Gastrointest Endosc ; 99(4): 525-536.e3, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37951280

RESUMEN

BACKGROUND AND AIMS: Guidelines recommend emergent or urgent EGD for esophageal food impaction (EFI), but data on how time to EGD impacts the risk of adverse events remain limited. We determined whether EFI-to-EGD time was associated with adverse events. METHODS: In this retrospective cohort study of patients with endoscopically confirmed EFI, adverse events were classified as esophageal (mucosal tear, bleeding, perforation) or extraesophageal (aspiration, respiratory compromise, hypotension, arrhythmia). Esophageal perforation and extraesophageal adverse events requiring intensive care unit admission were classified as serious adverse events. Baseline characteristics, event details, and procedural details were compared between patients with and without adverse events. Multivariable logistic regression was performed to assess for an association between EFI-to-EGD time and adverse events. RESULTS: Of 188 patients with EFI, 22 (12%) had any adverse event and 2 (1%) had a serious adverse event. Patients with adverse events were older and more likely to have an esophageal motility disorder, to tolerate secretions at presentation, and to have a higher American Society of Anesthesiologists score. EFI-to-EGD time was similar in those with and without adverse events. On multivariable analysis, EFI-to-EGD time was not associated with adverse events (odds ratio, 1.00 [95% confidence interval, .97-1.04] for 1-hour increments; odds ratio, 1.03 [95% confidence interval, .86-1.24] for 6-hour increments). Results were similar after stratifying by eosinophilic esophagitis status and after adjusting for possible confounders. CONCLUSIONS: Because the time from EFI to EGD is not associated with adverse events, emergent EGD for EFI may be unnecessary, and other considerations may determine EGD timing.


Asunto(s)
Trastornos de Deglución , Esofagitis Eosinofílica , Humanos , Trastornos de Deglución/etiología , Estudios Retrospectivos , Esofagitis Eosinofílica/complicaciones , Endoscopía Gastrointestinal/efectos adversos
17.
Gastrointest Endosc ; 99(6): 1027-1031.e6, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38316224

RESUMEN

BACKGROUND AND AIMS: A novel multisegmented esophageal fully covered self-expandable metal stent (FCSEMS) was designed to reduce stent migration, which is seen in up to 30% of patients. The goal of this study was to evaluate the safety and efficacy of the multisegmented FCSEMS. METHODS: This multicenter prospective study aimed to include 30 patients undergoing palliative stent placement. Efficacy, defined as technically successful stent placement and dysphagia scores, and safety, defined as the number of adverse events (AEs) and serious AEs (SAEs), were measured. RESULTS: The study was prematurely terminated due to safety concerns after including 23 patients (mean ± standard deviation age, 72 ± 10 years; 78% male). Stent placement was technically successful in 21 patients (91%), and dysphagia scores had improved in all patients with successful stent placement. SAEs were reported in 16 (70%) patients. Stent-related mortality occurred in 3 patients (13%). CONCLUSIONS: The multisegmented FCSEMS successfully treated malignant dysphagia. The study was prematurely terminated, however, because stent placement was associated with a relatively high SAE rate. (Clinical trial registration number: NCT04415463.).


Asunto(s)
Trastornos de Deglución , Neoplasias Esofágicas , Estudios de Factibilidad , Cuidados Paliativos , Stents Metálicos Autoexpandibles , Humanos , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Masculino , Anciano , Femenino , Stents Metálicos Autoexpandibles/efectos adversos , Cuidados Paliativos/métodos , Estudios Prospectivos , Neoplasias Esofágicas/complicaciones , Anciano de 80 o más Años , Persona de Mediana Edad , Resultado del Tratamiento
18.
Gastrointest Endosc ; 100(3): 417-428.e1, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38431105

RESUMEN

BACKGROUND AND AIMS: The diagnosis of achalasia is associated with an average delay of 2 years. Endoscopic features may prompt an earlier diagnosis. We aimed to develop and test a novel endoscopic score, CARS, for the prediction of achalasia. METHODS: Part 1: Twenty endoscopic videos were taken from patients undergoing endoscopy for dysphagia or reflux. A survey with videos and endoscopic criteria options was distributed to 6 esophagologists and 6 general gastroenterologists. Inter-rater reliability (IRR) was measured and logistic regression was used to evaluate predictive performance. Three rounds of review were conducted to select the final score of 4 components. Part 2: A retrospective review was conducted for consecutive patients who had comprehensive esophageal testing. Each patient had a CARS endoscopic score calculated based on findings reported at endoscopy. RESULTS: From a video review and analysis of score components, IRR ranged from 0.23 to 0.57 for score components. The final CARS score was selected based on the following 4 components: Contents, Anatomy, Resistance, and Stasis. In a mixed-effects model, the mean score across raters was higher for achalasia compared with nonachalasia subjects (4.44 vs 0.87; P < .01). In part 2 of the study, achalasia patients had a higher mean CARS score compared with those with no or ineffective motility disorder (mean 4.1 vs 1.3; P < .01). CONCLUSIONS: We developed a CARS score based on reliability performance in a video-based survey and tested the score in a clinical setting. The CARS score performed well in predicting achalasia.


Asunto(s)
Acalasia del Esófago , Acalasia del Esófago/diagnóstico , Humanos , Estudios Retrospectivos , Reproducibilidad de los Resultados , Femenino , Grabación en Video , Masculino , Esofagoscopía/métodos , Persona de Mediana Edad , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Modelos Logísticos , Reflujo Gastroesofágico/diagnóstico , Adulto , Variaciones Dependientes del Observador , Anciano
19.
Endoscopy ; 56(1): 22-30, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37536365

RESUMEN

BACKGROUND: Esophageal stenting is an important intervention for managing malignant and benign dysphagia, with stent migration representing a common drawback. This systematic review with meta-analysis aimed to assess the benefit of stent fixation over nonfixation. METHODS: A systematic search was performed in MEDLINE, Cochrane, Scopus, and ClinicalTrials.gov databases until January 2023 for comparative studies evaluating the migration rates of esophageal stents with versus without (control) fixation. The primary outcome was migration rate. Secondary outcomes included adverse event rate. A subgroup analysis stratified the results based on different fixation techniques: suturing, over-the-scope (OTS) clipping, and through-the-scope (TTS) clipping. Meta-analysis was based on a random effects model and the results were reported as odds ratios (ORs) with 95 %CIs. RESULTS: 10 studies (1014 patients) were included. The rate of stent migration was significantly lower after fixation (OR 0.20, 95 %CI 0.11-0.37; I2  = 59 %, P = 0.01). The adverse event rate was similar between fixation and control groups (OR 0.65, 95 %CI 0.28-1.52; I2  = 55 %, P = 0.06). In the subgroup analysis, all fixation techniques remained superior to nonfixation of stents (suturing OR 0.23, 95 %CI 0.10-0.53; OTS clips OR 0.31, 95 %CI 0.17-0.58; TTS clips OR 0.10, 95 %CI 0.03-0.38); however, only the OTS and TTS clip groups achieved nonsignificant heterogeneity (I2  = 0 %, P = 0.67 and P = 0.73, respectively). No difference between techniques was recorded for migration rates. CONCLUSION: Esophageal stent fixation was associated with significantly lower migration rates compared with nonfixation of stents, regardless of fixation technique and stenting indication.


Asunto(s)
Trastornos de Deglución , Stents , Humanos , Stents/efectos adversos , Trastornos de Deglución/etiología , Trastornos de Deglución/cirugía , Resultado del Tratamiento
20.
Muscle Nerve ; 70(1): 140-147, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38742544

RESUMEN

INTRODUCTION/AIMS: Evaluations of pulmonary, cough, and swallow function are frequently performed to assess disease progression in amyotrophic lateral sclerosis (ALS), yet the relationship between these functions remains unknown. We therefore aimed to determine relationships between these measures in individuals with ALS. METHODS: One hundred individuals with ALS underwent standardized tests: forced vital capacity (FVC), maximum expiratory/inspiratory pressure (MEP, MIP), voluntary cough peak expiratory flow (PEF), and videofluoroscopic swallow evaluation (VF). Duplicate raters completed independent, blinded ratings using the Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) scale. Descriptives, Spearman's Rho correlations, Kruskal-Wallis analyses, and Pearson's chi-squared tests were completed. RESULTS: Mean and standard deviation across pulmonary and cough measures were FVC: 74.2% predicted (± 22.6), MEP: 91.6 cmH2O (± 46.4), MIP cmH2O: 61.1 (± 28.9), voluntary PEF: 352.7 L/min (± 141.6). DIGEST grades included: 0 (normal swallowing): 31%, 1 (mild dysphagia): 48%, 2 (moderate dysphagia): 10%, 3 (severe dysphagia): 10%, and 4 (life-threatening dysphagia): 1%. Positive correlations were observed: MEP-MIP: r = .76, MIP-PEF: r = .68, MEP-PEF: r = .61, MIP-FVC: r = .60, PEF-FVC: r = .49, and MEP-FVC: r = .46, p < .0001. MEP (p = .009) and PEF (p = .04) differed across DIGEST safety grades. Post hoc analyses revealed significant between group differences in MEP and PEF across DIGEST safety grades 0 versus 1 and grades 0 versus 3, (p < .05). DISCUSSION: In this cohort of individuals with ALS, pulmonary function, and voluntary cough were associated. Expiratory metrics (MEP, PEF) were diminished in individuals with unsafe swallowing, increasing their risk for effectively defending the airway.


Asunto(s)
Esclerosis Amiotrófica Lateral , Tos , Trastornos de Deglución , Deglución , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/complicaciones , Masculino , Tos/fisiopatología , Tos/etiología , Femenino , Persona de Mediana Edad , Anciano , Deglución/fisiología , Trastornos de Deglución/fisiopatología , Trastornos de Deglución/etiología , Capacidad Vital/fisiología , Adulto , Pulmón/fisiopatología , Pulmón/diagnóstico por imagen , Fluoroscopía , Pruebas de Función Respiratoria
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