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1.
Annu Rev Neurosci ; 43: 315-336, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32101484

RESUMO

All mammals must suckle and swallow at birth, and subsequently chew and swallow solid foods, for optimal growth and health. These initially innate behaviors depend critically upon coordinated development of the mouth, tongue, pharynx, and larynx as well as the cranial nerves that control these structures. Disrupted suckling, feeding, and swallowing from birth onward-perinatal dysphagia-is often associated with several neurodevelopmental disorders that subsequently alter complex behaviors. Apparently, a broad range of neurodevelopmental pathologic mechanisms also target oropharyngeal and cranial nerve differentiation. These aberrant mechanisms, including altered patterning, progenitor specification, and neurite growth, prefigure dysphagia and may then compromise circuits for additional behavioral capacities. Thus, perinatal dysphagia may be an early indicator of disrupted genetic and developmental programs that compromise neural circuits and yield a broad range of behavioral deficits in neurodevelopmental disorders.


Assuntos
Animais Lactentes/fisiologia , Transtornos de Deglutição/patologia , Rede Nervosa/fisiologia , Faringe/patologia , Animais , Comportamento/fisiologia , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Humanos , Faringe/fisiologia
2.
N Engl J Med ; 390(24): 2252-2263, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38924732

RESUMO

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.).


Assuntos
Anticorpos Monoclonais Humanizados , Esofagite Eosinofílica , Eosinófilos , Humanos , Esofagite Eosinofílica/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Masculino , Método Duplo-Cego , Feminino , Adolescente , Pessoa de Meia-Idade , Adulto , Criança , Adulto Jovem , Idoso , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/tratamento farmacológico , Contagem de Leucócitos , Subunidade alfa de Receptor de Interleucina-5/antagonistas & inibidores
3.
N Engl J Med ; 387(25): 2317-2330, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36546624

RESUMO

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.).


Assuntos
Anticorpos Monoclonais Humanizados , Transtornos de Deglutição , Esofagite Eosinofílica , Adolescente , Adulto , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Transtornos de Deglutição/tratamento farmacológico , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/patologia , Método Duplo-Cego , Esofagite Eosinofílica/complicações , Esofagite Eosinofílica/tratamento farmacológico , Esofagite Eosinofílica/patologia , Injeções Subcutâneas , Resultado do Tratamento , Criança , Adulto Jovem
4.
Proc Natl Acad Sci U S A ; 119(29): e2121095119, 2022 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-35858334

RESUMO

The coordination of swallowing with breathing, in particular inspiration, is essential for homeostasis in most organisms. While much has been learned about the neuronal network critical for inspiration in mammals, the pre-Bötzinger complex (preBötC), little is known about how this network interacts with swallowing. Here we activate within the preBötC excitatory neurons (defined as Vglut2 and Sst neurons) and inhibitory neurons (defined as Vgat neurons) and inhibit and activate neurons defined by the transcription factor Dbx1 to gain an understanding of the coordination between the preBötC and swallow behavior. We found that stimulating inhibitory preBötC neurons did not mimic the premature shutdown of inspiratory activity caused by water swallows, suggesting that swallow-induced suppression of inspiratory activity is not directly mediated by the inhibitory neurons in the preBötC. By contrast, stimulation of preBötC Dbx1 neurons delayed laryngeal closure of the swallow sequence. Inhibition of Dbx1 neurons increased laryngeal closure duration and stimulation of Sst neurons pushed swallow occurrence to later in the respiratory cycle, suggesting that excitatory neurons from the preBötC connect to the laryngeal motoneurons and contribute to the timing of swallowing. Interestingly, the delayed swallow sequence was also caused by chronic intermittent hypoxia (CIH), a model for sleep apnea, which is 1) known to destabilize inspiratory activity and 2) associated with dysphagia. This delay was not present when inhibiting Dbx1 neurons. We propose that a stable preBötC is essential for normal swallow pattern generation and disruption may contribute to the dysphagia seen in obstructive sleep apnea.


Assuntos
Deglutição , Optogenética , Respiração , Centro Respiratório , Animais , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Interneurônios/fisiologia , Laringe , Camundongos , Camundongos Transgênicos , Neurônios Motores/fisiologia , Centro Respiratório/fisiologia
5.
Gut ; 73(3): 398-406, 2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38050037

RESUMO

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.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Adolescente , Adulto , Humanos , Anticorpos Monoclonais Humanizados/efeitos adversos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/tratamento farmacológico , Método Duplo-Cego , Endoscopia , Esofagite Eosinofílica/tratamento farmacológico , Glucocorticoides/uso terapêutico , Resultado do Tratamento
6.
Br J Cancer ; 130(11): 1795-1802, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38555316

RESUMO

BACKGROUND: Modifying public awareness of oesophageal cancer symptoms might help to decrease late-stage diagnosis and, in turn, improve cancer outcomes. This study aimed to explore oesophageal cancer symptom awareness and determinants of lower awareness and anticipated time to help-seeking. METHODS: We invited 18,156 individuals aged 18 to 75 years using random sampling of the nationwide Dutch population registry. A cross-sectional web-based survey containing items adapted from the Awareness and Beliefs about Cancer measure (i.e., cancer symptom awareness, anticipated time to presentation with dysphagia, health beliefs, and sociodemographic variables) was filled out by 3106 participants (response rate: 17%). Descriptive statistics were calculated and logistic regression analyses were performed to explore determinants of awareness and anticipated presentation (dichotomised as <1 month or ≥1 month). RESULTS: The number of participants that recognised dysphagia as a potential symptom of cancer was low (47%) compared with symptoms of other cancer types (change in bowel habits: 77%; change of a mole: 93%; breast lump: 93%). In multivariable analyses, non-recognition of dysphagia was associated with male gender (OR 0.50, 95% CI 0.43-0.58), lower education (OR 0.44, 0.35-0.54), and non-western migration background (OR 0.43, 0.28-0.67). Anticipated delayed help-seeking for dysphagia was associated with not recognising it as possible cancer symptom (OR 1.58, 1.27-1.97), perceived high risk of oesophageal cancer (OR 2.20, 1.39-3.47), and negative beliefs about oesophageal cancer (OR 1.86, 1.20-2.87). CONCLUSION: Our findings demonstrate a disconcertingly low public awareness of oesophageal cancer symptoms. Educational interventions targeting groups with decreased awareness and addressing negative cancer beliefs may lead to faster help-seeking behaviour, although additional studies are needed to determine the effect on clinical cancer outcomes.


Assuntos
Neoplasias Esofágicas , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Humanos , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/psicologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Idoso , Estudos Transversais , Adolescente , Adulto Jovem , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Inquéritos e Questionários , Transtornos de Deglutição/epidemiologia , Conscientização , Fatores de Tempo , Países Baixos/epidemiologia , Comportamento de Busca de Ajuda
7.
Am J Physiol Gastrointest Liver Physiol ; 327(1): G105-G116, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38772905

RESUMO

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.


Assuntos
Capsaicina , Deglutição , Refluxo Gastroesofágico , Animais , Refluxo Gastroesofágico/fisiopatologia , Suínos , Deglutição/efeitos dos fármacos , Capsaicina/farmacologia , Esôfago/fisiopatologia , Esôfago/efeitos dos fármacos , Esôfago/inervação , Eletromiografia , Faringe/fisiopatologia , Animais Recém-Nascidos , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Orofaringe/fisiopatologia , Alimentação com Mamadeira , Feminino , Fluoroscopia
8.
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
9.
Am J Gastroenterol ; 119(1): 97-106, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37883488

RESUMO

INTRODUCTION: Guidelines advise esophageal motility testing for dysphagia when structural disorders are ruled out, but cost concerns impede adoption. We evaluated cost-effective positioning of esophageal motility testing in the algorithm to evaluate esophageal dysphagia. METHODS: We developed a decision analytic model comparing 3 strategies: (i) esophageal manometry, (ii) screening impedance planimetry followed by esophageal manometry if needed, or (iii) nonalgorithmic usual care. Diagnostic test accuracy was adapted to expected rates of esophageal motility disorders in general gastroenterology populations. We modeled routine testing for all patients with nonstructural/mechanical dysphagia compared with selective testing with strong suspicion for achalasia. Cost outcomes were defined on national commercial and Medicare datasets stratified on age and sex. Health outcomes were modeled on populations with achalasia. The time horizon was 1 year. RESULTS: Motility testing was preferred over nonalgorithmic usual care due to cost savings rather than health gains. To commercial insurers, routine esophageal manometry for nonstructural/mechanical dysphagia would be cost-saving below a reimbursed cost of $2,415. Screening impedance planimetry would be cost saving below a reimbursed cost of $1,130. The limit for reimbursed costs would be lower for patients older than 65 years to achieve cost savings mainly due to insurance. Sex did not significantly influence cost-effectiveness. Patients and insurers preferred routine screening impedance planimetry before manometry when the index of suspicion for achalasia was below 6%. DISCUSSION: Aligning with practice guidelines, routine esophageal motility testing seems cost saving to patients and insurers compared with nonalgorithmic usual care to evaluate nonstructural/mechanical dysphagia. Choice of testing should be guided by index of suspicion.


Assuntos
Transtornos de Deglutição , Acalasia Esofágica , Transtornos da Motilidade Esofágica , Estados Unidos , Humanos , Idoso , Transtornos de Deglutição/diagnóstico , Acalasia Esofágica/diagnóstico , Análise Custo-Benefício , Medicare , Transtornos da Motilidade Esofágica/diagnóstico , Manometria , Endoscopia Gastrointestinal , Impedância Elétrica
10.
Am J Gastroenterol ; 119(6): 1066-1073, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38299582

RESUMO

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.


Assuntos
Esofagite Eosinofílica , Imunoglobulina G , Humanos , Esofagite Eosinofílica/dietoterapia , Esofagite Eosinofílica/imunologia , Esofagite Eosinofílica/sangue , Feminino , Masculino , Imunoglobulina G/sangue , Adulto , Estudos Prospectivos , Pessoa de Meia-Idade , Hipersensibilidade Alimentar/dietoterapia , Hipersensibilidade Alimentar/complicações , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/sangue , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/dietoterapia , Esofagoscopia , Eosinófilos/imunologia , Adulto Jovem , Dieta de Eliminação
11.
Radiology ; 310(1): e223334, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38289217

RESUMO

HISTORY: A 76-year-old woman with a history of rheumatoid arthritis, Sjögren syndrome, and hypertension presented with a headache, fever, and dysphagia. The patient was taking prednisone and leflunomide to treat rheumatoid arthritis. Her headache was primarily left sided and occasionally radiated to the occipital region. The patient had a high-grade fever spike, with a temperature of 104°F (40°C). Results of a prior lumbar puncture and temporal artery biopsy from an outside hospital were negative. Findings of a neurologic examination were unremarkable. Oropharyngeal examination for dysphagia revealed minimal pharyngeal motility, with pooling of food in the pharynx, which was thought to be due to cranial nerve dysfunction. Laboratory analysis revealed that, except for anemia, complete blood count parameters were within normal limits. C-reactive protein level (49.7 mg/L; reference range, 0.0-8.0 mg/L), erythrocyte sedimentation rate (>140 mm/h with Westergren method; reference range, 0-27 mm/h), and brain-type natriuretic peptide level (145 pg/mL; reference range, 0-100 pg/mL) were elevated. Blood and urine cultures were negative. A lumbar puncture was performed, which revealed cloudy cerebrospinal fluid (CSF), with an elevated CSF protein level (78 mg/dL; reference range, 7.0-35.0 mg/dL) and a low CSF glucose level (37 mg/dL [2.05 mmol/L]; reference range, 45-70 mg/dL [2.50-3.89 mmol/L]); otherwise, CSF encephalopathy, an autoimmune panel, and cultures were negative. MRI and CT scans of the brain with paranasal sinus were performed (Figs 1-3). Nasal endoscopy-guided drainage of the preclival fluid collection was performed, and biopsy of nasopharyngeal tissue was performed. Fluid culture revealed the growth of Candida albicans, as well as Pseudomonas and Enterobacter aerogenes. The patient received fluconazole, ceftriaxone, vancomycin, and metronidazole. Follow-up MRI was performed after 2 weeks (Fig 4).


Assuntos
Artrite Reumatoide , Transtornos de Deglutição , Humanos , Feminino , Idoso , Punção Espinal , Biópsia , Febre , Cefaleia
12.
Curr Opin Oncol ; 36(3): 128-135, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38573201

RESUMO

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.


Assuntos
Transtornos de Deglutição , Neoplasias de Cabeça e Pescoço , Humanos , Quimiorradioterapia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/prevenção & controle , Gastrostomia , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Boca , Orofaringe , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto
13.
BMC Cancer ; 24(1): 648, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802747

RESUMO

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.


Assuntos
Transtornos de Deglutição , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Xerostomia , Humanos , Transtornos de Deglutição/etiologia , Masculino , Xerostomia/etiologia , Feminino , Carcinoma Nasofaríngeo/radioterapia , Carcinoma Nasofaríngeo/complicações , Carcinoma Nasofaríngeo/patologia , Pessoa de Meia-Idade , Radioterapia de Intensidade Modulada/efeitos adversos , Radioterapia de Intensidade Modulada/métodos , Estudos Retrospectivos , Seguimentos , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/complicações , Adulto , Idoso , Lesões por Radiação/etiologia , Lesões por Radiação/prevenção & controle , Deglutição , Glândulas Salivares/efeitos da radiação , Glândulas Salivares/patologia , Glândulas Salivares/diagnóstico por imagem , Dosagem Radioterapêutica , Prognóstico , Adulto Jovem
14.
Epilepsia ; 65(5): 1374-1382, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38456606

RESUMO

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.


Assuntos
Transtornos de Deglutição , Humanos , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/diagnóstico , Feminino , Masculino , Idoso , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Adulto , Epilepsias Parciais/complicações , Convulsões/complicações , Convulsões/epidemiologia , Convulsões/diagnóstico , Estudos Retrospectivos
15.
Gastrointest Endosc ; 99(4): 525-536.e3, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37951280

RESUMO

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.


Assuntos
Transtornos de Deglutição , Esofagite Eosinofílica , Humanos , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Esofagite Eosinofílica/complicações , Endoscopia Gastrointestinal/efeitos adversos
16.
Gastrointest Endosc ; 99(6): 1027-1031.e6, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38316224

RESUMO

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.).


Assuntos
Transtornos de Deglutição , Neoplasias Esofágicas , Estudos de Viabilidade , Cuidados Paliativos , Stents Metálicos Autoexpansíveis , Humanos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Masculino , Idoso , Feminino , Stents Metálicos Autoexpansíveis/efeitos adversos , Cuidados Paliativos/métodos , Estudos Prospectivos , Neoplasias Esofágicas/complicações , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Resultado do Tratamento
17.
Endoscopy ; 56(1): 22-30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37536365

RESUMO

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.


Assuntos
Transtornos de Deglutição , Stents , Humanos , Stents/efeitos adversos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/cirurgia , Resultado do Tratamento
18.
Muscle Nerve ; 70(1): 140-147, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38742544

RESUMO

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.


Assuntos
Esclerose Lateral Amiotrófica , Tosse , Transtornos de Deglutição , Deglutição , Humanos , Esclerose Lateral Amiotrófica/fisiopatologia , Esclerose Lateral Amiotrófica/complicações , Masculino , Tosse/fisiopatologia , Tosse/etiologia , Feminino , Pessoa de Meia-Idade , Idoso , Deglutição/fisiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/etiologia , Capacidade Vital/fisiologia , Adulto , Pulmão/fisiopatologia , Pulmão/diagnóstico por imagem , Fluoroscopia , Testes de Função Respiratória
19.
Nutr Cancer ; 76(3): 271-278, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38206128

RESUMO

Objective: We sought to identify factors that can predict esophageal cancer (EC) patients at high risk of requiring feeding tube insertion. Methods: A retrospective cohort review was conducted, including all patients diagnosed with EC at our cancer center from 2013 to 2018. Multivariate logistic regression was performed comparing the group that required a reactive feeding tube insertion to those who did not require any feeding tube insertion to identify risk factors. Results: A total of 350 patients were included in the study, and 132/350 (38%) patients received a feeding tube. 50 out of 132 (38%) patients had feeding tube inserted reactively. Severe dysphagia (OR 19.9, p < 0.001) at diagnosis and decision to undergo chemotherapy (OR 2.8, p = 0.008) appeared to be predictors for reactive feeding tube insertion. The reactive insertion group had a 7% higher rate of complications relating to feeding tube. Conclusion: Severe dysphagia at diagnosis and undergoing chemotherapy were identified as risk factors for requiring a feeding tube. Ultimately, the aim is to create a predictive tool that utilizes these risks factors to accurate identify high-risk patients who may benefit from prophylactic feeding tube insertion.


Assuntos
Transtornos de Deglutição , Neoplasias Esofágicas , Humanos , Transtornos de Deglutição/etiologia , Estudos Retrospectivos , Nutrição Enteral/efeitos adversos , Intubação Gastrointestinal/efeitos adversos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/complicações
20.
Eur J Neurol ; 31(7): e16303, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38634169

RESUMO

BACKGROUND AND PURPOSE: Swallowing is a complex task, moderated by a sophisticated bilateral network including multiple supratentorial regions, the brainstem and the cerebellum. To date, conflicting data exist about whether focal lesions to the cerebellum are associated with dysphagia. Therefore, the aim of the study was to evaluate dysphagia prevalence, recovery and dysphagia pattern in patients with ischaemic cerebellar stroke. METHODS: A retrospective analysis of patients consecutively admitted to an academic stroke centre with ischaemic stroke found only in the cerebellum was performed. The presence of dysphagia was the primary end-point and was assessed by a speech-language pathologist, according to defined criteria. Dysphagia pattern was evaluated by analysing the videos of the flexible endoscopic evaluation of swallowing. Brain imaging was used to identify lesion size and location associated with dysphagia. RESULTS: Between January 2016 and December 2021, 102 patients (35.3% female) with a mean age of 52.8 ± 17.3 years were included. Thirteen (12.7%) patients presented with dysphagia. The most frequently observed flexible endoscopic evaluation of swallowing phenotype was premature spillage (n = 7; 58.3%), whilst significant residues or aspiration did not occur. One patient died (7.7%); the other patients showed improvement of dysphagia and one patient (7.7%) was discharged with dietary restrictions. CONCLUSIONS: Although the involvement of the cerebellum in deglutition has become increasingly evident, isolated lesions to the cerebellum are less likely to cause clinically relevant and persisting dysphagia compared to other brain regions. The observed dysphagia pattern shows a lack of coordination and control, resulting in premature spillage or fragmented bolus transfer in some patients.


Assuntos
Transtornos de Deglutição , AVC Isquêmico , Fenótipo , Humanos , Feminino , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Transtornos de Deglutição/epidemiologia , Masculino , Pessoa de Meia-Idade , Idoso , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/epidemiologia , Estudos Retrospectivos , Prevalência , Adulto , Recuperação de Função Fisiológica/fisiologia , Cerebelo/diagnóstico por imagem , Cerebelo/patologia , Doenças Cerebelares/complicações , Doenças Cerebelares/epidemiologia , Doenças Cerebelares/diagnóstico por imagem
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