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BACKGROUND: Diabetes Mellitus (DM) is known to induce a wide range of harmful effects on several organs, notably leading to ineffective esophageal motility (IEM). However, the relationship between DM and IEM is not fully elucidated. We aimed to determine the relationship between DM and IEM and to evaluate the impact of DM's end organ complications on IEM severity. METHODS: A multicenter cohort study of consecutive patients undergoing high-resolution esophageal manometry (HREM) was performed. We reviewed medical records of patients diagnosed with IEM using HREM, encompassing data on demographics, DM history, antidiabetic and other medications as well as comorbidities. KEY RESULTS: Two hundred and forty six subjects met the inclusion criteria. There was no significant difference in any of the HREM parameters between diabetics and nondiabetics. Out of 246 patients, 92 were diabetics. Diabetics with neuropathy presented a significantly lower distal contractile integral (DCI) value compared to those without neuropathy (248.2 ± 226.7 mmHg·cm·sec vs. 375.6 ± 232.4 mmHg·cm·sec; p = 0.02) Similarly, the DCI was lower in diabetics with retinopathy compared to those without retinopathy (199.9 ± 123.1 mmHg·cm·sec vs. 335.4 ± 251.7 mmHg·cm·sec; p = 0.041). Additionally, a significant difference was observed in DCI values among DM patients with ≥2 comorbidities compared to those without comorbidities (224.8 ± 161.0 mmHg·cm·sec vs. 394.2 ± 243.6 mmHg·cm·sec; p = 0.025). Around 12.6% of the variation in DCI could be explained by its linear relationship with hemoglobin A1c (HbA1c), with a regression coefficient (ß) of -55.3. CONCLUSION & INFERENCES: DM is significantly associated with IEM in patients with neuropathy, retinopathy, or multiple comorbidities. These results are pivotal for tailoring patient-specific management approaches.
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Complicaciones de la Diabetes , Trastornos de la Motilidad Esofágica , Manometría , Humanos , Trastornos de la Motilidad Esofágica/fisiopatología , Trastornos de la Motilidad Esofágica/epidemiología , Trastornos de la Motilidad Esofágica/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Complicaciones de la Diabetes/epidemiología , Complicaciones de la Diabetes/fisiopatología , Estudios de Cohortes , Neuropatías Diabéticas/fisiopatología , Neuropatías Diabéticas/epidemiología , Diabetes Mellitus/epidemiología , Adulto , Estudios RetrospectivosRESUMEN
INTRODUCTION: Gastroesophageal reflux disease (GERD) is the most common diagnosis seen in outpatient gastroenterology clinics. The diagnosis is made by a variable combination of symptoms, response to acid suppressive therapy, endoscopic evaluation, and pH testing. In this review, we evaluate how to utilize various reflux testing in clinical practice based on current evidence. AREAS COVERED: Ambulatory reflux monitoring is a recognized diagnostic tool for clinical decision making in patients with/without established GERD, persistent reflux symptoms, and lack of response to proton pump inhibitor (PPI) therapy. Standard evaluation approaches include 24-hour pH or impedance monitoring via transnasal catheter, prolonged (48 to 96 hour) wireless pH monitoring, and the recently developed mucosal integrity testing. Testing using one of these methods allows for measurement of acid exposure, frequency of reflux, and to phenotype patients to personalize treatment recommendations. EXPERT OPINION: The primary goal of future studies should be to simplify ambulatory reflux monitoring, reduce diagnostic latency, improve patient tolerance, and to obtain clinical outcomes-based studies. The current paradigm of reflux testing is vastly complex with multiple modalities and shifting cutoffs of pH abnormality that lead to high economic burden on the society.
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Monitorización del pH Esofágico , Reflujo Gastroesofágico , Humanos , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Impedancia Eléctrica , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Heartburn is the most common symptom seen in gastroenterology practice. We aimed to optimize cost-effective evaluation and management of heartburn. METHODS: We developed a decision analytic model from insurer and patient perspectives comparing 4 strategies for patients failing empiric proton pump inhibitors (PPIs): (1) PPI optimization without testing, (2) endoscopy with PPI optimization for all patients, (3) endoscopy with PPI discontinuation when erosive findings are absent, and (4) endoscopy/ambulatory reflux monitoring with PPI discontinuation as appropriate for phenotypic management. Health outcomes were respectively defined on systematic reviews of clinical trials. Cost outcomes were defined on Centers for Medicare and Medicaid Services databases and commercial multipliers for direct healthcare costs, and national observational studies evaluating healthcare utilization. The time horizon was 1 year. All testing was performed off PPI. RESULTS: PPI optimization without testing cost $3784/y to insurers and $3128 to patients due to lower work productivity and suboptimal symptom relief. Endoscopy with PPI optimization lowered insurer costs by $1020/y and added 11 healthy days/y by identifying erosive reflux disease. Endoscopy with PPI discontinuation added 11 additional healthy days/y by identifying patients without erosive reflux disease that did not need PPI. By optimizing phenotype-guided treatment, endoscopy/ambulatory reflux monitoring with a trial of PPI discontinuation was the most effective of all strategies (gaining 22 healthy days/y) and saved $2183 to insurers and $2396 to patients. CONCLUSIONS: Among patients with heartburn, endoscopy with ambulatory reflux monitoring (off PPI) optimizes cost-effective management by matching treatment to phenotype. When erosive findings are absent, trialing PPI discontinuation is more cost-effective than optimizing PPI.
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BACKGROUND: Prenatal ethanol exposure hinders oxidative stress-mediated neuroblast/neural progenitor cell proliferation by inhibiting G1-S transition, a process vital to neocortical development. We previously showed that ethanol elicits this redox imbalance by repressing cystathionine γ-lyase (CSE), the rate-limiting enzyme in the transsulfuration pathway in fetal brain and cultured cerebral cortical neurons. However, the mechanism by which ethanol impacts the CSE pathway in proliferating neuroblasts is not known. We conducted experiments to define the effects of ethanol on CSE regulation and the molecular signaling events that control this vital pathway. This enabled us to develop an intervention to prevent the ethanol-associated cytostasis. METHODS: Spontaneously immortalized undifferentiated E18 rat neuroblasts from brain cerebral cortex were exposed to ethanol to mimic an acute consumption pattern in humans. We performed loss- and gain-of-function studies to evaluate whether NFATc4 is a transcriptional regulator of CSE. The neuroprotective effects of chlorogenic acid (CGA) against the effects of ethanol were assessed using ROS and GSH/GSSG assays as measures of oxidative stress, transcriptional activation of NFATc4, and expression of NFATc4 and CSE by qRT-PCR and immunoblotting. RESULTS: Ethanol treatment of E18-neuroblast cells elicited oxidative stress and significantly reduced CSE expression with a concomitant decrease in NFATc4 transcriptional activation and expression. In parallel, inhibition of the calcineurin/NFAT pathway by FK506 exaggerated ethanol-induced CSE loss. In contrast, NFATc4 overexpression prevented loss of ethanol-induced CSE. CGA increased and activated NFATc4, amplified CSE expression, rescued ethanol-induced oxidative stress, and averted the cytostasis of neuroblasts by rescuing cyclin D1 expression. CONCLUSIONS: These findings demonstrate that ethanol can perturb CSE-dependent redox homeostasis by impairing the NFATc4 signaling pathway in neuroblasts. Notably, ethanol-associated impairments were rescued by genetic or pharmacological activation of NFATc4. Furthermore, we found a potential role for CGA in mitigating the ethanol-related neuroblast toxicity with a compelling connection to the NFATc4/CSE pathway.
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BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions that enhance patient-physician communication by encouraging patients to ask questions during consultations. AIM: The aim of this study was to develop a preliminary achalasia-specific QPL created by esophageal experts. METHODS: The QPL content was derived through a modified Delphi method consisting of 2 rounds. In round 1, experts provided 5 answers to the prompts "What general questions should patients ask when given a new diagnosis of achalasia" and "What questions do I not hear patients asking, but given my expertise, I believe they should be asking?" In round 2, experts rated questions on a 5-point Likert scale. Questions considered "essential" or "important" were accepted into the QPL. Feedback regarding the QPL was obtained in a pilot study wherein patients received the QPL before their consultation and completed surveys afterwards. RESULTS: Nineteen esophageal experts participated in both rounds. Of 148 questions from round 1, 124 (83.8%) were accepted into the QPL. These were further reduced to 56 questions to minimize redundancy. Questions were categorized into 6 themes: "What is achalasia," "Risks with achalasia," "Symptom management in achalasia," "Treatment of achalasia," "Risk of reflux after treatment," and "Follow-up after treatment." Nineteen patients participated in the pilot, most of whom agreed that the QPL was helpful (84.2%) and recommended its wider use (84.2%). CONCLUSIONS: This is the first QPL developed specifically for adults with achalasia. Although well-received in a small pilot, follow-up studies will incorporate additional patient feedback to further refine the QPL content and assess its usability, acceptability, and feasibility.
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Acalasia del Esófago , Humanos , Adulto , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/terapia , Proyectos Piloto , Técnica Delphi , Participación del Paciente , Comunicación , Encuestas y Cuestionarios , Relaciones Médico-PacienteRESUMEN
BACKGROUND & AIMS: Studies with limited sample sizes have investigated association of chronic opioid use with motility disorders of esophagogastric junction and esophageal body peristalsis. Our aims were to use a large cohort of patients to assess (1) the impact of opioid exposure on clinical and manometric characteristics, and (2) the association of opioid exposure with higher long-term symptom burden. METHODS: Patients recruited from a tertiary medical center who underwent high-resolution manometry (HRM) between 2007 and 2018 were included. Demographics, opiate exposure, clinical symptoms, and HRM parameters were compared. Patient-Reported Outcomes Measurement Information System-Gastrointestinal swallowing domain (PROMIS-GI swallowing domain) and Eckardt score were administered via phone interviews in patients with hypercontractile esophagus (HE) or distal esophageal spasm (DES) to determine long-term symptom burden between opioid and nonopioid users. RESULTS: Our cohort included 4075 patients (869 with opiate exposure with median morphine milligram equivalent [interquartile range] of 30 [10-45]). Patients in the opioid group were significantly more likely to have dysphagia (65% vs 51%, P < .01) and diagnosis of DES (11% vs 5%, P < .01) and HE (9% vs 3%, P < .01). Partial opioid agonists were not associated with motility abnormalities. Patients on opioids had significantly higher symptom burden on median (interquartile range) follow-up of 8.9 years (5.8-10.4) post manometric diagnosis with median PROMIS-GI swallowing domain score of 21.5 (17-25) compared with the nonopioid group at 15 (9.8-21, P = .03). CONCLUSIONS: Nearly 2 of 3 patients with opioid exposure undergoing HRM have dysphagia and more than 25% of them with dysphagia as the primary symptom have a diagnosis of either DES or HE. Opioid users with spastic disorders have higher symptom burden long-term compared with nonopioid users.
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Trastornos de Deglución , Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Alcaloides Opiáceos , Analgésicos Opioides/efectos adversos , Trastornos de Deglución/inducido químicamente , Trastornos de Deglución/etiología , Acalasia del Esófago/complicaciones , Trastornos de la Motilidad Esofágica/diagnóstico , Esfínter Esofágico Inferior , Humanos , Manometría , Estudios RetrospectivosRESUMEN
Non-obstructive dysphagia (NOD) is defined as symptomatic dysphagia in patients with negative endoscopic and radiographic workup. The management of NOD remains controversial as there is a discrepancy between different guidelines and clinical practice. Despite the lack of high-quality studies, empiric dilation for NOD is a common clinical practice among endoscopists and the approach varies between different clinical centers. In this review, we summarize the published literature on empiric dilation for NOD and propose a management algorithm for offering empiric dilation to patients presenting with dysphagia.
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Trastornos de Deglución , Humanos , Dilatación , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Resultado del Tratamiento , ManometríaRESUMEN
Dysphagia is a common symptom with significant impact on quality of life. Our diagnostic armamentarium was primarily limited to endoscopy and barium esophagram until the advent of manometric techniques in the 1970s, which provided the first reliable tool for assessment of esophageal motor function. Since that time, significant advances have been made over the last 3 decades in our understanding of various esophageal motility disorders due to improvement in diagnostics with high-resolution esophageal manometry. High-resolution esophageal manometry has improved the sensitivity for detecting achalasia and has also enhanced our understanding of spastic and hypomotility disorders of the esophageal body. In this review, we discuss the current approach to diagnosis and therapeutics of various esophageal motility disorders.
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Acalasia del Esófago , Trastornos de la Motilidad Esofágica , Endoscopía Gastrointestinal , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/terapia , Trastornos de la Motilidad Esofágica/diagnóstico , Trastornos de la Motilidad Esofágica/terapia , Humanos , Manometría/métodos , Calidad de VidaRESUMEN
BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, enhancing the patient-physician communication by encouraging patients to ask relevant questions during a consultation. Recently, a preliminary 78 question gastroesophageal reflux disease (GERD) specific QPL was created by 12 esophageal experts through a modified Delphi (RAND/University of California, Los Angeles) technique. Patients' perspectives and opinions on each question, however, had not been accounted for in the preliminary expert' version. AIM: The aim was to modify a preliminary experts' QPL, specific to adults with GERD, following patient perspectives and opinions. METHODS: A preliminary GERD QPL was modified through patient input and opinions. Thirty-eight patients with a clinical diagnosis of GERD followed at Stanford University Esophageal Clinic between January and November 2019 were consented to modify the preliminary 78 question expert QPL version. After receiving the QPL in Qualtrics (Provo, UT) by a direct e-mail invitation, patients independently rated questions on a 5-point Likert scale, where 1="should not be included," 2="unimportant," 3="don't know/depends," 4="important," and 5="essential." Questions were accepted for inclusion in the QPL with an a priori interagreement of 80% ranking in the range of 4 to 5. At the end, patients were encouraged to propose additional questions to incorporate into the QPL by open-endedly asking "Are there questions we didn't ask, that you think we should?" RESULTS: Twenty-three patients with GERD (19 female, median age 64) fully participated and modified the existing QPL (60.5%). Of the 78 questions from the preliminary GERD QPL, 66 questions (84.6%) were accepted for inclusion. The question with the highest agreement among patients rating a question as essential consisted of "what habits, food, and drinks do I have to avoid?" (82.6%). Questions eliminated because of disagreement included "What is the natural history of GERD," "Do I have a high chance to die from my Barrett's?," and "Why are you prescribing an antidepressant to treat my GERD?" Nine patients suggested additional questions totaling to 16 separate questions, including "What type of surgeries are there to help GERD?," "What stage is my GERD?," "What are the odds/percentage of getting cancer from GERD?" Incorporating the suggested questions, the final GERD QPL-created by esophageal experts and modified by patients-consisted of 82 questions. CONCLUSION: Esophageal experts and GERD patients have a high level of agreement on important questions, though there is some variation in perspective. Future studies can simplify this list and measure the impact of a shared GERD QPL on patients' decisional conflict and perceived involvement in care.
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Reflujo Gastroesofágico , Participación del Paciente , Adulto , Comunicación , Femenino , Reflujo Gastroesofágico/diagnóstico , Humanos , Persona de Mediana Edad , Relaciones Médico-Paciente , Encuestas y CuestionariosAsunto(s)
Sistema Nervioso Entérico/virología , Acalasia del Esófago/virología , Esfínter Esofágico Inferior/inervación , Herpesvirus Humano 3/patogenicidad , Infección por el Virus de la Varicela-Zóster/virología , Activación Viral , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Sistema Nervioso Entérico/fisiopatología , Acalasia del Esófago/diagnóstico , Acalasia del Esófago/fisiopatología , Femenino , Interacciones Huésped-Patógeno , Humanos , Masculino , Factores de Riesgo , Infección por el Virus de la Varicela-Zóster/complicaciones , Infección por el Virus de la Varicela-Zóster/diagnósticoRESUMEN
Heartburn is a common symptom in clinical practice, but as many as 70% of patients have normal findings from upper endoscopy. Most of these patients have nonerosive reflux disease (NERD) or functional esophageal disorders. NERD is the most common phenotype of gastroesophageal reflux disease, and functional heartburn is the most common cause for refractory heartburn. In patients with NERD, symptoms arise from gastroesophageal reflux and esophageal hypersensitivity, whereas in patients with functional heartburn, symptoms result from esophageal hypersensitivity. A diagnosis of NERD requires endoscopy and reflux testing, whereas a diagnosis of functional heartburn also requires esophageal manometry. NERD is treated most commonly with medical, endoscopic, and surgical antireflux approaches, whereas functional heartburn as well as NERD can be treated with neuromodulators, psychological intervention, and complementary medicine options.
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Reflujo Gastroesofágico , Pirosis , Monitorización del pH Esofágico , Reflujo Gastroesofágico/complicaciones , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/terapia , Gastroscopía , Pirosis/diagnóstico , Pirosis/etiología , Pirosis/terapia , Humanos , Inhibidores de la Bomba de Protones/uso terapéuticoAsunto(s)
Dolor Crónico/patología , Endocannabinoides/metabolismo , Infecciones por VIH/complicaciones , Neuralgia/patología , Receptores de Cannabinoides/metabolismo , Amidohidrolasas/metabolismo , Animales , Asialoglicoproteínas/metabolismo , Dolor Crónico/tratamiento farmacológico , Dolor Crónico/etiología , Modelos Animales de Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Proteína gp120 de Envoltorio del VIH/metabolismo , Infecciones por VIH/virología , VIH-1/metabolismo , Humanos , Lectinas Tipo C/metabolismo , Masculino , Marihuana Medicinal/farmacología , Marihuana Medicinal/uso terapéutico , Proteínas de la Membrana/metabolismo , Ratones , Neuralgia/tratamiento farmacológico , Neuralgia/etiología , Factores Sexuales , Asta Dorsal de la Médula Espinal/patologíaAsunto(s)
Neoplasias Abdominales/patología , Neoplasias de Células Germinales y Embrionarias/patología , Neoplasias Testiculares/patología , Neoplasias Abdominales/diagnóstico por imagen , Neoplasias Abdominales/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioterapia Adyuvante , Cisplatino/uso terapéutico , Etopósido/uso terapéutico , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neoplasias de Células Germinales y Embrionarias/diagnóstico por imagen , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias Testiculares/diagnóstico por imagen , Neoplasias Testiculares/terapia , Tomografía Computarizada por Rayos XRESUMEN
Laryngopharyngeal reflux and atypical manifestations of gastroesophageal reflux disease have a high economic and social burden in the United States. There is increasing research supporting the reflex theory and hypersensitivity syndrome underlying this disease pathophysiology. Novel diagnostic biomarkers have gained more traction in the search for a more reliable diagnostic tool, but further research is needed. Current standard-of-care treatment relies on proton pump inhibitor therapy. Antireflux surgery is usually not recommended. Neuromodulators and treatments targeting specific neuronal receptors are discussed. A diagnostic algorithm is proposed for the evaluation of laryngeal symptoms suspected to be related to extraesophageal reflux disease.
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Sistemas de Apoyo a Decisiones Clínicas , Reflujo Gastroesofágico/diagnóstico , Reflujo Laringofaríngeo/diagnóstico , Algoritmos , Diagnóstico Diferencial , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Reflujo Laringofaríngeo/tratamiento farmacológico , Laringe/fisiopatología , Neurotransmisores/uso terapéutico , Inhibidores de la Bomba de Protones/uso terapéuticoRESUMEN
BACKGROUND: Question prompt lists (QPLs) are structured sets of disease-specific questions intended for patient use, encouraging patients to ask questions to facilitate their consultation with their physician. AIM: The aim of this study was to develop a QPL specific to adults with gastroesophageal reflux disease (GERD), created by esophageal experts. METHODS: The QPL content (78 questions) was derived through a modified Delphi method consisting of 2 rounds. In round 1, 18 esophageal experts provided 5 answers to the prompt "What you wish your patients would ask" and "What questions do patients often not ask, that I wish they would ask?" In round 2, the experts rated each question on a 5-point Likert scale, and responses rated as "essential" or "important," determined by an a priori threshold of ≥4.0, were accepted for the QPL. RESULTS: Twelve esophageal experts participated. Of 143 questions from round 1, 110 (76.9%) were accepted for inclusion in the QPL, meeting a median value of ≥4.0, and, subsequently, it reduced to 78, minimizing redundancy. Median values ranged between 4.0 and 5.0, with the highest agreement median (5.0) for questions asking dosing and timing of proton pump inhibitor therapy, and surveillance in Barrett's. Questions were categorized into the following categories: "What does this illness mean," "lifestyle modifications," "general treatment," "treatment with proton pump inhibitors," "What I should expect for my future," and "Barrett's." The largest number of questions covered lifestyle modifications (21.8%), with the highest agreement median (5.0) for "How helpful are lifestyle modifications in GERD?" CONCLUSIONS: A preliminary GERD-specific QPL, the first of its kind, was developed by esophageal experts. Modification after more patient consultation and feedback is planned in subsequent versions to create a GERD-QPL for eventual use in clinical gastroenterology.
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Reflujo Gastroesofágico , Relaciones Médico-Paciente , Adulto , Comunicación , Técnica Delphi , Reflujo Gastroesofágico/diagnóstico , Reflujo Gastroesofágico/tratamiento farmacológico , Humanos , Encuestas y CuestionariosRESUMEN
Altered barrier function is a part of celiac disease (CeD) pathophysiology that we currently cannot reliably measure. Catheter-based mucosal integrity (MI) is an endoscopic technology that has identified altered esophageal barrier function in esophageal disease.1 The aim of this study was to evaluate feasibility, safety, and clinical utility of measuring duodenal integrity with an MI catheter in patients with and without CeD.