RESUMEN
Cryptococcus neoformans is a widely distributed opportunistic pathogenic fungus. While C. neoformans commonly infects immunocompromised individuals, it can also affect those who are immunocompetent. Transmission of C. neoformans primarily occurs through the respiratory tract, leading to the development of meningitis. The mortality rate of Cryptococcal meningitis is high, and treatment options are limited. Cryptococcus neoformans infections pose a significant public health threat and currently lack targeted and effective response strategies. This study aimed to screen T lymphocyte (cytotoxic T lymphocyte and helper T lymphocyte) and B lymphocyte epitopes derived from four C. neoformans antigens and develop two multi-epitope vaccines by combining them with various adjuvants. Molecular docking results demonstrated that the vaccines bind stably to Toll-like receptor 4 ( and induce innate immunity. The credibility of the molecular docking results was validated through subsequent molecular dynamics simulations. Furthermore, the results of immune simulation analyses underscored the multi-epitope vaccine's capability to effectively induce robust humoral and cellular immune responses within the host organism. These two vaccines have demonstrated theoretical efficacy against C. neoformans infection as indicated by computer analysis. Nevertheless, additional experimental validation is essential to substantiate the protective efficacy of the vaccines.
A multi-epitope Cryptococcus neoformans vaccine covering the most common A and D phenotypes was designed using bioinformatics methods.
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Biología Computacional , Cryptococcus neoformans , Epítopos de Linfocito B , Epítopos de Linfocito T , Vacunas Fúngicas , Simulación del Acoplamiento Molecular , Cryptococcus neoformans/inmunología , Cryptococcus neoformans/química , Vacunas Fúngicas/inmunología , Epítopos de Linfocito T/inmunología , Epítopos de Linfocito B/inmunología , Humanos , Criptococosis/inmunología , Criptococosis/prevención & control , Receptor Toll-Like 4/inmunología , Antígenos Fúngicos/inmunología , Simulación de Dinámica Molecular , Adyuvantes Inmunológicos , InmunoinformáticaRESUMEN
Acinetobacter baumannii is a gram-negative bacillus prevalent in nature, capable of thriving under various environmental conditions. As an opportunistic pathogen, it frequently causes nosocomial infections such as urinary tract infections, bacteremia, and pneumonia, contributing to increased morbidity and mortality in clinical settings. Consequently, developing novel vaccines against Acinetobacter baumannii is of utmost importance. In our study, we identified 10 highly conserved antigenic proteins from the NCBI and UniProt databases for epitope mapping. We subsequently screened and selected 8 CTL, HTL, and LBL epitopes, integrating them into three distinct vaccines constructed with adjuvants. Following comprehensive evaluations of immunological and physicochemical parameters, we conducted molecular docking and molecular dynamics simulations to assess the efficacy and stability of these vaccines. Our findings indicate that all three multi-epitope mRNA vaccines designed against Acinetobacter baumannii are promising; however, further animal studies are required to confirm their reliability and effectiveness.
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Acinetobacter baumannii , Vacunas Bacterianas , Biología Computacional , Acinetobacter baumannii/inmunología , Acinetobacter baumannii/genética , Vacunas Bacterianas/inmunología , Vacunas Bacterianas/genética , Biología Computacional/métodos , Epítopos/inmunología , Epítopos/química , Simulación del Acoplamiento Molecular , Infecciones por Acinetobacter/prevención & control , Infecciones por Acinetobacter/inmunología , Mapeo Epitopo , Vacunas de ARNm , Simulación de Dinámica Molecular , Humanos , ARN Mensajero/genética , ARN Mensajero/inmunología , Antígenos Bacterianos/inmunología , Antígenos Bacterianos/genética , Proteínas Bacterianas/inmunología , Proteínas Bacterianas/genética , Proteínas Bacterianas/químicaRESUMEN
The emergence of Cryptococcus neoformans has posed an undeniable burden to many regions worldwide, with its strains mainly entering the lungs through the respiratory tract and spreading throughout the body. Limitations of drug regimens, such as high costs and limited options, have directed our attention toward the promising field of vaccine development. In this study, the subtractive proteomics approach was employed to select target proteins from databases that can accurately cover serotypes A and D of the Cryptococcus neoformans. Further, two multi-epitope vaccines consisting of T and B cell epitopes were demonstrated that they have good structural stability and could bind with immune receptor to induce desired immune responses in silico. After further evaluation, these vaccines show the potential for large-scale production and applicability to the majority of the population of the world. In summary, these two vaccines have been theoretically proven to combat Cryptococcus neoformans infections, awaiting further experimental validation of their actual protective effects.
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Biología Computacional , Criptococosis , Cryptococcus neoformans , Epítopos de Linfocito B , Vacunas Fúngicas , Proteómica , Cryptococcus neoformans/inmunología , Vacunas Fúngicas/inmunología , Proteómica/métodos , Criptococosis/inmunología , Criptococosis/prevención & control , Humanos , Biología Computacional/métodos , Epítopos de Linfocito B/inmunología , Epítopos de Linfocito T/inmunología , Animales , Antígenos Fúngicos/inmunología , Proteínas Fúngicas/inmunología , Proteínas Fúngicas/química , Desarrollo de Vacunas , InmunoinformáticaRESUMEN
BACKGROUND: There is a lack of data on the epidemiology of IBS in pregnant and postpartum patients in the United States. METHODS: A retrospective claims analysis was conducted in a cohort of 1,618,379 patients with ≥1 delivery hospitalization between 2013-2019 utilizing ICD-9 and ICD-10 codes after merging inpatient and outpatient claims. Obstetric, psychological, and other medical comorbidities were also examined. KEY RESULTS: The prevalence of IBS in our cohort was 1.38%. Pregnant and postpartum patients with IBS were more likely to have psychological comorbidities including depression (OR 2.93, CI 2.83-3.03), postpartum depression (OR 3.00, CI 2.91-3.09), and anxiety (OR 3.74, CI 3.64-3.84). They were also more likely to have migraines (OR 3.04, CI 2.94-3.15) and connective tissue disease or autoimmune disease (OR 3.54, CI 3.22-3.89). CONCLUSION: The prevalence of IBS in pregnant and postpartum patients in a large claims database was 1.38%. Pregnant and postpartum patients with IBS have a higher odd of psychological comorbidities in addition to medical comorbidities such as migraines, connective tissue, and autoimmune disease. Future studies should focus on validating and characterizing the impact and directionality of co-existing comorbidities on IBS severity and the development of new-onset IBS during pregnancy and the postpartum period.
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Comorbilidad , Síndrome del Colon Irritable , Complicaciones del Embarazo , Humanos , Femenino , Embarazo , Síndrome del Colon Irritable/epidemiología , Síndrome del Colon Irritable/psicología , Adulto , Prevalencia , Estudios Retrospectivos , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , Estados Unidos/epidemiología , Trastornos Migrañosos/epidemiología , Trastornos Migrañosos/psicología , Periodo Posparto/psicología , Adulto Joven , Depresión Posparto/epidemiologíaRESUMEN
The maternal inheritance of mitochondria is a widely accepted paradigm, and mechanisms that prevent paternal mitochondria transmission to offspring during spermatogenesis and postfertilization have been described. Although certain species do retain paternal mitochondria, the factors affecting paternal mitochondria inheritance in these cases are unclear. More importantly, the evolutionary benefit of retaining paternal mitochondria and their ultimate fate are unknown. Here we show that transplanted exogenous paternal D. yakuba mitochondria can be transmitted to offspring when maternal mitochondria are dysfunctional in D. melanogaster. Furthermore, we show that the preserved paternal mitochondria are functional, and can be stably inherited, such that the proportion of paternal mitochondria increases gradually in subsequent generations. Our work has important implications that paternal mitochondria inheritance should not be overlooked as a genetic phenomenon in evolution, especially when paternal mitochondria are of significant differences from the maternal mitochondria or the maternal mitochondria are functionally abnormal. Our results improve the understanding of mitochondrial inheritance and provide a new model system for its study.
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ADN Mitocondrial , Drosophila , Masculino , Animales , ADN Mitocondrial/genética , Drosophila/genética , Genes Mitocondriales , Drosophila melanogaster/genética , Mitocondrias/genéticaRESUMEN
BACKGROUND: Digital rectal examination should be performed prior to anorectal manometry; however, real-world data is lacking. AIMS: Characterize real world rates of digital rectal and their sensitivity for detecting dyssynergia compared to anorectal manometry and balloon expulsion test. METHODS: A retrospective single-center study was conducted to examine all patients who underwent anorectal manometry for chronic constipation between 2021 and 2022 at one tertiary center with motility expertise. Primary outcomes consisted of the rate of digital rectal exam prior to anorectal manometry; and secondary outcomes included the sensitivity of digital rectal exam for dyssynergic defecation. RESULTS: Only 42.3% of 142 patients had digital rectal examinations prior to anorectal manometry. Overall sensitivity for detecting dyssynergic defecation was 46.4%, but significantly higher for gastroenterology providers (p = .004), and highest for gastroenterology attendings (82.6%). CONCLUSIONS: Digital rectal examination is infrequently performed when indicated for chronic constipation. Sensitivity for detecting dyssynergic defecation may be impacted by discipline and level of training.
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Defecación , Recto , Humanos , Estudios Retrospectivos , Manometría , Estreñimiento/diagnóstico , Tacto Rectal , Ataxia , Canal AnalRESUMEN
BACKGROUND AND AIMS: Endoscopic-related injuries (ERIs) for gastroenterologists are common and can impact longevity of an endoscopic career. This study examines sex differences in the prevalence of ERIs and ergonomic training during gastroenterology fellowship. METHODS: A 56-item anonymous survey was sent to 709 general and advanced endoscopy gastroenterology fellows at 73 U.S. training programs between May and June 2022. Demographic information was collected along with questions related to endoscopic environment, ergonomic instruction, technique, equipment availability, and ergonomic knowledge. Responses of female and male gastroenterology fellows were compared using χ2 and Fisher exact tests. RESULTS: Of the 236 respondents (response rate, 33.9%), 113 (44.5%) were women and 123 (52.1%) were men. Female fellows reported on average smaller hand sizes and shorter heights. More female fellows reported endoscopic equipment was not ergonomically optimized for their use. Additionally, more female fellows voiced preference for same-gender teachers and access to dial extenders and well-fitting lead aprons. High rates of postendoscopy pain were reported by both sexes, with significantly more women experiencing neck and shoulder pain. Trainees of both sexes demonstrated poor ergonomic awareness with an average score of 68% on a 5-point knowledge-based assessment. CONCLUSIONS: Physical differences exist between male and female trainees, and current endoscopic equipment may not be optimized for smaller hand sizes. This study highlights the urgent need for formal ergonomic training for trainees and trainers with consideration of stature and hand size to enhance safety, comfort, and equity in the training and practice of endoscopy.
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Gastroenterólogos , Gastroenterología , Humanos , Masculino , Femenino , Gastroenterología/educación , Caracteres Sexuales , Endoscopía Gastrointestinal/educación , Gastroenterólogos/educación , Encuestas y Cuestionarios , Becas , ErgonomíaRESUMEN
BACKGROUND: Healthy China is a nationwide health strategy aiming at improving health from diverse dimensions, and strengthening high-quality assessment is essential for its stimulation. However, there is limited evidence in the surveillance of the actual performance of the initiative at regional levels. This study innovatively proposes a two-step surveillance process which comprehensively monitors Healthy China Initiative based on regional realities, thus provides guidance for policymaking. METHODS: A flexible indicator system was firstly developed basing on Delphi survey and focus group discussions. And then the Analysis Hierarchical Process and the TOPSIS method were used to determine the weights of indicators and calculate comprehensive indexes as the surveillance outcomes. A pilot study was conducted in a typical area in China to verify the applicability of the process. RESULTS: Following the surveillance process and basing on the implementation of Healthy China Initiative in the target region, an indicator system comprised of 5 domains and 23 indicators with weights was first developed specifically for the pilot area. Then 1848 interagency data of the study area were collected from 8 provincial institutions/departments to calculate the indexes and ranks of the five domains which were health level, healthy living, disease prevention and control, health service, and healthy environment. The outcomes showed that Healthy China Initiative in the pilot area had been constantly improved since the strategy proposed, while there were still issues to be tackled such as the deficient monitoring mechanisms and unevenly development progress. CONCLUSIONS: This study proposed a pragmatic surveillance process with indicators which could be tailored for specific context of target regions and produce meaningful surveillance outcomes to inform decision-making for policymakers, and also provided a theoretical foundation as well as empirical evidence for further health strategies and plannings assessment studies.
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Proceso de Jerarquía Analítica , Impulso (Psicología) , China , Proyectos Piloto , Promoción de la SaludRESUMEN
BACKGROUND: Despite their high prevalence and burden, disorders of gut-brain interaction (DGBI) are undertaught and underrepresented in medical curricula. We evaluated the exposure of UK gastroenterology trainees to DGBI and their comfort managing these conditions. METHODS: An electronic survey was distributed to trainees via UK training program directors. The survey included questions on stage of training; subspecialty interest; access to DGBI training opportunities, and comfort levels with DGBI diagnosis and management. Responses were compared between junior and senior trainees, by subspecialty interest (luminal and non-luminal), by geographical region, and training program size. KEY RESULTS: One hundred twelve trainees from across the UK participated (21.4% of national training post holders). Exposure to DGBI lectures (32.8% junior vs. 73.3% senior trainees, p = 0.00003) and clinics (9.0% junior vs. 42.2% senior trainees, p = 0.00003), increased with seniority. Regardless of seniority, most trainees were rarely comfortable making a DGBI diagnosis (39.5% senior vs. 33.9% junior trainees, p = 0.69), and were not comfortable initiating neuromodulators (50% senior vs. 25.8% junior trainees, p = 0.08). Trainees without a luminal subspecialty interest (50%) accessed fewer DGBI clinics (p = 0.04), had less communication skills training (p = 0.04) and were less likely to have been observed during DGBI consultations (p = 0.002). Responses were similar across UK regions and did not differ between smaller and larger programs. CONCLUSIONS & INFERENCES: DGBI training opportunities are limited in UK gastroenterology training across training grades. Most trainees lack confidence with DGBI diagnosis and management. Urgent interventions need to be targeted at all stages of training to ensure DGBI competencies for future gastroenterologists and improve patient outcomes.
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Gastroenterología , Humanos , Gastroenterología/educación , Educación de Postgrado en Medicina/métodos , Encuestas y Cuestionarios , Reino Unido , EncéfaloRESUMEN
BACKGROUND: Forty percent of individuals globally meet Rome IV criteria for a disorder of gut-brain interaction (DGBI). The global burden of pain across these disorders has not been characterized. METHODS: Our study included 54,127 respondents from the 26 Internet survey countries. Prescription pain medication usage was selected as the proxy for pain. The associations between prescription pain medications and the environmental, sociodemographic, psychosocial, and DGBI diagnosis variables were investigated using the multivariate generalized robust Poisson regression model. KEY RESULTS: Respondents with DGBI used prescription pain medications at higher rates than those without a DGBI diagnosis with pooled prevalence rate of 14.8% (95% confidence interval [CI], 14.4-15.3%), varying by country from 6.8% to 25.7%. The pooled prevalence ratio of prescription pain medication usage in respondents with and without DGBI was 2.2 (95% CI: 2.1-2.4). Factors associated with higher prevalence of pain medication usage among respondents with a DGBI diagnosis included living in a small community, increased anxiety, depression or somatization, increased stress concern or embarrassment about bowel functioning and having more than one anatomic DGBI diagnosis. CONCLUSION: 14.8% of patients globally with at least one diagnosis of DGBI were on prescription pain medications with wide geographic variation, about twice as many as their counterparts without a diagnosis of DGBI. Environmental, sociodemographic, and individual factors may influence clinicians to consider personalized, multimodal approaches to address pain in patients with DGBI.
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Encéfalo , Dolor , Humanos , Dolor/tratamiento farmacológico , Trastornos de Ansiedad , Encuestas y Cuestionarios , PrescripcionesRESUMEN
PURPOSE: Fecal microbiota transplant (FMT) is increasingly performed for Clostridioides difficile infection (CDI), although long-term efficacy and safety data are limited and are focused on results from academic medical centers rather than private settings where most patients receive care. METHODS: Medical records of 165 patients who received FMTs for CDI were reviewed from an academic medical center and an adjacent, unaffiliated private practice. Of these patients, 68 also completed a survey regarding their long-term disease course and interval health. RESULTS: CDI resolution occurred in 81.3% (100/123) at the academic center and 95.2% (40/42) in the private setting. Private practice patients were more likely to present with recurrent, rather than refractory, CDI (92.9% vs. 66.7% P <0.001). Those from the academic center were more likely to have comorbid IBD, recent hospitalization, recent proton pump inhibitor use, ongoing immunosuppression, and inpatient FMT (all P values <0.05).Among surveyed patients, 29.4% developed interval comorbidities or changes to pre-existing conditions after a median follow-up of 33.7 months (IQR 13.2 to 44.3 mo). Of 30 patients requiring subsequent antibiotics, 13.3% suffered CDI relapse. All subjects who had initially responded to FMT but had a subsequent CDI (17.9%, 10/56) responded to another FMT. CONCLUSIONS: In a real-world setting, patients who underwent FMT at academic centers differed significantly in clinical characteristics from those treated at a private practice. In both settings, FMT is an effective treatment for CDI not responding to standard therapies, even after subsequent antibiotic use. New diagnoses following FMT, however, are common and merit further exploration.
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BACKGROUND: Total proctocolectomy with ileal pouch anal anastomosis (IPAA) for medically refractory ulcerative colitis or dysplasia may be associated with structural and inflammatory complications. However, even in their absence, defecatory symptoms secondary to dyssynergic defecation or fecal incontinence may occur. Although anorectal manometry is well established as the diagnostic test of choice for defecatory symptoms, its utility in the assessment of patients with IPAA is less established. In this systematic review, we critically evaluate the existing evidence for anopouch manometry (APM). METHODS: A total of 393 studies were identified, of which 6 studies met all inclusion criteria. Studies were not pooled given different modalities of testing with varying outcome measures. RESULTS: Overall, less than 10% of symptomatic patients post-IPAA were referred to APM. The prevalence of dyssynergic defecation as defined by the Rome IV criteria in symptomatic patients with IPAA ranged from 47.0% to 100%. Fecal incontinence in patients with IPAA was characterized by decreased mean and maximal resting anal pressure on APM, as well as pouch hyposensitivity. The recto-anal inhibitory reflex was absent in most patients with and without incontinence. CONCLUSION: Manometry alone is an imperfect assessment of pouch function in patients with defecatory symptoms, and confirmatory testing may need to be performed with dynamic imaging.
Dyssynergic defecation and fecal incontinence are increasingly being recognized in symptomatic patients with ileal pouch anal anastomosis. Manometry alone is an imperfect assessment of pouch function in patients with defecatory symptoms, and confirmatory testing may need to be performed with dynamic imaging.
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Colitis Ulcerosa , Reservorios Cólicos , Incontinencia Fecal , Proctocolectomía Restauradora , Humanos , Incontinencia Fecal/etiología , Proctocolectomía Restauradora/efectos adversos , Anastomosis Quirúrgica/efectos adversos , Recto/cirugía , Colitis Ulcerosa/complicaciones , Canal Anal/cirugíaRESUMEN
The strong suppression of Aedes albopictus on two Guangzhou islands in China has been successfully achieved by releasing males with an artificial triple-Wolbachia infection. However, it requires the use of radiation to sterilize residual females to prevent population replacement. To develop a highly effective tool for dengue control, we tested a standalone incompatible insect technique (IIT) to control A. albopictus in the urban area of Changsha, an inland city where dengue recently emerged. Male mosquitoes were produced in a mass rearing facility in Guangzhou and transported over 670 km under low temperature to the release site. After a once-per-week release with high numbers of males (phase I) and a subsequent twice-per-week release with low numbers of males (phase II), the average numbers of hatched eggs and female adults collected weekly per trap were reduced by 97% and 85%, respectively. The population suppression caused a 94% decrease in mosquito biting at the release site compared to the control site. Remarkably, this strong suppression was achieved using only 28% of the number of males released in a previous trial. Despite the lack of irradiation to sterilize residual females, no triple-infected mosquitoes were detected in the field post release based on the monitoring of adult and larval A. albopictus populations for two years, indicating that population replacement was prevented. Our results support the feasibility of implementing a standalone IIT for dengue control in urban areas.
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Aedes , Dengue , Animales , Masculino , Femenino , Control de Mosquitos/métodos , Dinámica Poblacional , Larva , Dengue/prevención & controlRESUMEN
Purpose of Review: The world's population is aging rapidly, with 40% of patients seen in US gastroenterology (GI) clinics being 60 years or older. Many gastrointestinal problems are more common or unique to the older adult because of progressive damage to the structure and function of the GI tract. Until recently, the epidemiology of disorders of gut-brain interaction (such as irritable bowel syndrome and functional dyspepsia) was not well-characterized. Recent Findings: Forty percent of persons worldwide have disorders of gut-brain interaction (DGBI), with varying global patterns of incidence in older adults. There are multiple first-line approaches to managing DGBI which can also be combined including pharmacologic (e.g., neuromodulators) and nonpharmacologic approaches including dietary therapies and brain-gut behavioral therapies. However, there are considerations clinicians must account for when offering each approach related to unique biopsychosocial factors in the older adult population. In this review, we aim to critically review recent literature on the pathophysiology, epidemiology, and special considerations for diagnosing and managing DGBI in the older adult population. Summary: There have been many advances in the management of DGBI over the past decades. Given the increase in the number of older adults in the USA and worldwide, there is an urgent need for evidence-based guidance to help providers guide comprehensive care for specifically our aging patient population with respect to DGBI.
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OBJECTIVES: This quality improvement project sought to enhance clinical information sharing for interhospital transfers to an inpatient hepatology service comprised of internal medicine resident frontline providers (housestaff) with the specific aims of making housestaff aware of 100% of incoming transfers and providing timely access to clinical summaries. INTERVENTIONS: In February 2020, an email notification system to senior medicine residents responsible for patient triage shared planned arrival time for patients pending transfer. In July 2020, a clinical data repository ("Transfer Log") updated daily by accepting providers (attending physicians and subspecialty fellows) became available to senior medicine residents responsible for triage. METHODS: Likert scale surveys were administered to housestaff before email intervention (pre) and after transfer log intervention (post). The time from patient arrival to team assignment (TTA) in the electronic medical record was used as a proxy for time to patient assessment and was measured pre- and postinterventions; >2 hours to TTA was considered an extreme delay. RESULTS: Housestaff reported frequency of access to clinical information as follows: preinterventions 4/31 (13%) sometimes/very often and 27/31 (87%) never/rarely; postinterventions 11/26 (42%) sometimes/very often and 15/26 (58%) never/rarely (p = 0.02). Preinterventions 12/39 (31%) felt "not at all prepared" versus 27/39 (69%) "somewhat" or "adequately"; postinterventions 2/24 (8%) felt "not at all prepared" versus 22/24 (92%) somewhat/adequately prepared (p = 0.06). There was a significant difference in mean TTA between pre- and posttransfer log groups (62 vs. 40 minutes, p = 0.01) and a significant reduction in patients with extreme delays in TTA post-email (18/180 pre-email vs. 7/174 post-email, p = 0.04). CONCLUSION: Early notification and increased access to clinical information were associated with better sense of preparedness for admitting housestaff, reduction in TTA, and reduced frequency of extreme delays in team assignment.
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Centros Médicos Académicos/normas , Comunicación en Salud/normas , Cuerpo Médico de Hospitales , Transferencia de Pacientes/normas , Centros de Atención Terciaria/normas , Registros Electrónicos de Salud/normas , Correo Electrónico , Gastroenterología/normas , Humanos , Internado y Residencia , Mejoramiento de la Calidad , Factores de Tiempo , Triaje/métodos , Triaje/normasRESUMEN
INTRODUCTION: Disorders of gut-brain interaction (DGBI) are highly prevalent, estimated to affect about 40% of the global population. Patients with DGBI are still inadequately treated and face stigma which adversely impacts their disease course. METHODS: A 12-question multiple-choice anonymous survey was distributed electronically to all adult gastroenterology fellowship program directors across the United States. Data were collected on demographics, training, attitudes, and knowledge in managing patients with DGBI. RESULTS: 9.8% and 15.9% of all trainees reported that their attendings and peers often demonstrated a dismissive attitude towards patients with DGBI, respectively. 21.4% of all trainees often felt frustrated or burned out when seeing patients with DGBI with increasing odds of burnout by years of training (OR 4.4 for F3 trainees, trainees in their third year of training). Significantly, more female trainees reported frustration and burnout when seeing patients with DGBI (p = 0.005). 28.6% of all trainees report they often do not want to see patients with DGBI in their outpatient GI practice, including 39.6% of F3 trainees. 27.1% of F3 trainees reported that they were uncomfortable with titrating neuromodulators and only 31.6% of all trainees were comfortable knowing when to refer to a gastropsychologist. DISCUSSION: Many trainees expressed some unwillingness and discomfort in managing patients with DGBI. Potential interventions will require a multi-pronged and longitudinal approach with education and training initiatives at the trainee level and beyond and exploring systemic healthcare delivery innovations to remove barriers.
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Gastroenterología , Adulto , Encéfalo , Femenino , Gastroenterología/educación , Humanos , Encuestas y Cuestionarios , Estados UnidosRESUMEN
Functional esophageal disorders (functional chest pain, functional heartburn, reflux hypersensitivity, globus, and functional dysphagia) are the disorders of gut-brain interactions (DGBI) and present with esophageal symptoms not associated with a structural, major motility or underlying inflammatory condition. Notably, many patients with the latter conditions may still experience esophageal symptoms beyond what could be attributed to their underlying disorders. Esophageal visceral hypersensitivity and hypervigilance are the two pathways which drive functional esophageal disorders and symptoms. These functional esophageal symptoms may be severe, leaving patients with impaired quality of life and inadequate treatment outcomes. Neuromodulators are the foundation of the pharmacologic approach of many of the functional esophageal disorders and symptoms, modulating both peripheral and central hyperalgesia. There is also emerging evidence for brain-gut behavioral therapies (BGBT) such as gut-directed hypnotherapy and cognitive behavior therapy for the treatment of a variety of DGBIs. In this issue of Neurogastroenterology and Motility, Hurtte et al. add to the literature on the effectiveness of BGBT in treating functional esophageal symptoms, showing multimodal therapy with pharmacologic and non-pharmacologic approaches led to improvement in health-related quality of life. In this review, we outline the mechanistic underpinnings of BGBT and review the existing evidence for BGBT for functional esophageal disorders and symptoms. We also highlight the future research directions and challenges for scaling these therapies.
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Enfermedades del Esófago , Calidad de Vida , Encéfalo , Pirosis/diagnóstico , HumanosRESUMEN
BACKGROUND: Immunocompromised patients are particularly vulnerable to Clostridioides difficile infection (CDI), hospitalizations and recurrences. Studies have shown that fecal microbiota transplant (FMT) is safe and effective in immunocompromised patients. AIMS: To examine the outcomes of FMT for CDI in a diverse cohort of immunocompromised patients stratified by medication class. METHODS: We performed a retrospective, long-term follow-up study of FMT in immunocompromised patients, including those undergoing chemotherapy, with inflammatory bowel disease (IBD) on immunomodulators, prior solid organ transplant on immunosuppressants, on chronic steroids 20 mg/day or higher for a minimum of three months, or HIV positive. Primary outcomes included adjusted primary cure rate within 8 weeks, as well as rates of non-response, recurrences, relapses and adverse events. Secondary outcomes included adjusted overall cure rate. Primary cure rate was defined as patients not requiring repeat CDI treatment within 8 weeks after index FMT, and overall cure rate was defined as resolution of CDI symptoms after index FMT or second FMT. RESULTS: Our cohort included 77 immunosuppressed patients (53.2% female, median age 39.1 years, range 7-95 years). The majority of our cohort were IBD patients on biologics (62.3%). Adjusting for colectomies and deaths, our primary and overall cure rates were 85.1% and 86.5%, respectively. Twelve patients received FMT for severe or fulminant CDI with a 3-month survival rate of 91.7%. 11.7% of patients experienced serious adverse events following FMT. CONCLUSIONS: Our study supports the efficacy and safety of FMT in immunocompromised patients, though future research is needed to further ascertain the potential effects of immunosuppression on FMT outcomes.