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PURPOSE OF REVIEW: To provide an up-to-date review on the clinical assessment of two important gastrointestinal problems with overlapping symptomatology but diverse cause and testing methods. Small intestinal bacterial overgrowth (SIBO) is characterized by the presence of excess bacteria in the small intestine associated with bloating, distention, gas, and diarrhea. Lactose intolerance is caused by lactase enzyme deficiency in the small bowel mucosa leading to lactose malabsorption and symptoms of bloating, gas, and diarrhea. RECENT FINDINGS: SIBO is assessed by hydrogen/methane breath test using glucose as a substrate and/or small bowel aspirate and culture but these tests have shortcomings. Consequently, several new diagnostic techniques, including novel capsule technologies and other approaches are being evaluated. Lactose intolerance can be assessed by hydrogen/methane breath test using lactose as a substrate, or small bowel mucosal lactase assay, genetic testing and lactose tolerance test, although the efficacy and practicality of these diagnostic modalities are not equal. SUMMARY: In clinical practice, gas, bloating, distention, pain, and diarrhea are common gastrointestinal symptoms that often remain unexplained when routine gastrointestinal endoscopy, imaging, and stool tests are negative. These patients should be evaluated for SIBO and/or food intolerances including lactose intolerance.
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Intolerância à Lactose , Testes Respiratórios/métodos , Diarreia/diagnóstico , Diarreia/etiologia , Humanos , Hidrogênio , Lactase , Intolerância à Lactose/diagnóstico , Intolerância à Lactose/microbiologia , MetanoRESUMO
Chronic intestinal pseudo-obstruction (CIPO) is a rare disorder characterized by an impairment of coordinated propulsive activity in the gastrointestinal (GI) tract, which clinically mimics mechanical intestinal obstruction. CIPO is the most severe and debilitating form of GI dysmotility. CIPO may be primary or be secondary to pathology at any level of the brain-gut axis as well as systemic disease. The clinical features of CIPO are pleomorphic and largely depend on the site and extent of the segment of the GI tract involved. The diagnostic approach includes the need for investigations to exclude mechanical GI obstruction, screening for causes of secondary CIPO and the identification of the disease phenotype as well as the prompt recognition and treatment of complications such as malnutrition and small intestinal bacterial overgrowth. In managing this disorder, a holistic, multidisciplinary approach is needed with judicious use of pharmacotherapeutic agents. While currently there are no specific therapeutic modalities for CIPO, treatment is largely directed at maintaining adequate nutrition and electrolyte balance and enhancing coordinated GI motility. Surgery should be avoided unless advisable for carefully selected patients and may include stoma formation. This narrative review provides a concise overview of the literature on this rare, severe and complex disorder, and highlights the need and areas for further research to improve both diagnostics and therapeutics.
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Motilidade Gastrointestinal , Pseudo-Obstrução Intestinal/terapia , Intestinos/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Técnicas de Diagnóstico do Sistema Digestório , Feminino , Microbioma Gastrointestinal , Humanos , Pseudo-Obstrução Intestinal/diagnóstico , Pseudo-Obstrução Intestinal/etiologia , Pseudo-Obstrução Intestinal/fisiopatologia , Intestinos/microbiologia , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
The enteric nervous system (ENS) is involved in the regulation of virtually all gut functions. Conditions referred to as enteric neuropathies are the result of various mechanisms including abnormal development, degeneration or loss of enteric neurons that affect the structure and functional integrity of the ENS. In the past decade, clinical and molecular research has led to important conceptual advances in our knowledge of the pathogenetic mechanisms of these disorders. In this review we consider ENS disorders from a clinical perspective and highlight the advancing knowledge regarding their pathophysiology. We also review current therapies for these diseases and present potential novel reparative approaches for their treatment.
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Constipação Intestinal/patologia , Sistema Nervoso Entérico/patologia , Trato Gastrointestinal/inervação , Trato Gastrointestinal/patologia , Pseudo-Obstrução Intestinal/patologia , Doença de Chagas/parasitologia , Doença de Chagas/patologia , Doença de Chagas/terapia , Constipação Intestinal/terapia , Acalasia Esofágica/patologia , Acalasia Esofágica/terapia , Trato Gastrointestinal/microbiologia , Trato Gastrointestinal/parasitologia , Doença de Hirschsprung/patologia , Doença de Hirschsprung/terapia , Humanos , Pseudo-Obstrução Intestinal/terapiaRESUMO
Background: Oropharyngeal dysphagia (OD) significantly impacts older individuals and neurologically compromised patients, hindering safe ingestion of food and liquids. Despite its prevalence, OD remains underdiagnosed and undertreated, leading to severe complications such as malnutrition, dehydration, respiratory infections, and aspiration pneumonia (AP), and increases hospital readmissions. Objectives: This study analyzes the intricate relationship between OD and various clinical complications in older individuals and patients with neurological disorders. Methods: Utilizing retrospective analysis and narrative review, our work consolidates findings from prior studies on Hospital de Mataro's dysphagia patient cohort. Revisiting OD's intricate association with clinical complications, it presents data via odds ratios (OR), incidence ratios (IR), and hazard ratios (HR) from univariate and multivariate analyses. Results: Five studies (2001-2014) involving 3,328 patients were scrutinized. OD exhibited independent and significant associations with various complications among older patients. Older individuals with OD faced heightened 1-month (ODDS 3.28) and 1-year (OR 3.42) mortality risks post-pneumonia diagnosis. OD correlated with a 2.72-fold risk of malnutrition, 2.39-fold risk of lower respiratory tract infections, 1.82-fold pneumonia readmissions (IR), and 5.07-fold AP readmissions (IR). Post-stroke OD is linked to neurological impairment (OR 3.38) and respiratory (OR 9.54) and urinary infections (OR 7.77), alongside extended hospital stays (beta coefficient 2.11). Conclusion: Oropharyngeal dysphagia causes and significantly exacerbates diverse clinical complications in older and post-stroke patients, emphasizing the urgent need for proactive identification, comprehensive assessment, and tailored management. Acknowledging OD's broader implications in general medical practice is pivotal to improving patient outcomes and healthcare quality.
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Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction (DGBI). IBS significantly impacts the quality of life of patients. Since its pathogenesis is unclear and can be multifactorial, it highlights the need for new and improved pharmaceutical drugs that not only improve bowel symptoms, but also address global IBS symptoms, such as abdominal pain. Tenapanor, a recently Food & Drug Administration (FDA)-approved medication for IBS with constipation (IBS-C), is a small molecule inhibitor of the sodium/hydrogen exchanger isoform 3 (NHE3) that inhibits the absorption of sodium and phosphate in the gastrointestinal tract, resulting in fluid retention and softer stool. Furthermore, tenapanor reduces intestinal permeability to improve visceral hypersensitivity and abdominal pain. Due to its recent approval, tenapanor was not included in the recent IBS guidelines, however, it may be considered for IBS-C patients failing first-line treatment of soluble fiber. In this review article, we aim to provide in-depth information to the reader regarding the design of tenapanor, its development through Phase I, II and III randomized clinical trials, and its role in the treatment of IBS-C.
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Constipated patients are frequently referred to gastroenterologists for symptoms refractory to lifestyle modifications and laxatives. Dyssynergic defecation, the dyscoordination of rectoanal, abdominal, and pelvic floor muscles to facilitate defecation, is a major cause of refractory primary constipation. Understanding of the diagnosis, evaluation, and management of dyssynergic defecation and other evacuation disorders will allow providers to effectively manage these patients. This review focuses on the definition, pathophysiology, evaluation, and treatment of dyssynergic defecation and other evacuation disorders. Emerging treatments for these disorders include home biofeedback therapy for dyssynergic defecation and translumbosacral neuromodulation therapy for levator ani syndrome.
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Constipação Intestinal , Defecação , Ataxia/diagnóstico , Ataxia/etiologia , Ataxia/terapia , Biorretroalimentação Psicológica , Constipação Intestinal/diagnóstico , Constipação Intestinal/etiologia , Constipação Intestinal/terapia , Defecação/fisiologia , Humanos , LaxantesRESUMO
BACKGROUND: Biofeedback therapy is useful for treatment of fecal incontinence (FI), but is not widely available and labor intensive. We investigated if home biofeedback therapy (HBT) is non-inferior to office biofeedback therapy (OBT). METHODS: Patients with FI (≥1 episode/week) were randomized to HBT or OBT for 6 weeks. HBT was performed daily using novel device that provided resistance training and electrical stimulation with voice-guided instructions. OBT consisted of six weekly sessions. Both methods involved anal strength, endurance, and coordination training. Primary outcome was change in weekly FI episodes. FI improvement was assessed with stool diaries, validated instruments (FISI, FISS, and ICIQ-B), and anorectal manometry using intention-to-treat analysis. KEY RESULTS: Thirty (F/M = 26/4) FI patients (20 in HBT, 10 in OBT) participated. Weekly FI episodes decreased significantly after HBT (Δ ± 95% confidence interval: 4.7 ± 1.8, compared with baseline, p = 0.003) and OBT (3.7 ± 1.6, p = 0.0003) and HBT was non-inferior to OBT (p = 0.2). The FISI and FISS scores improved significantly in HBT group (p < 0.02). Bowel pattern, bowel control, and quality of life (QOL) domains (ICIQ-B) improved significantly in HBT arm (p < 0.023). Resting and maximum squeeze sphincter pressures significantly improved in both HBT and OBT groups and sustained squeeze pressure in HBT, without group differences. CONCLUSIONS & INFERENCES: Home biofeedback therapy is non-inferior to OBT for FI treatment. Home biofeedback is safe, effective, improves QOL, and through increased access could facilitate improved management of FI.
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Biorretroalimentação Psicológica/métodos , Incontinência Fecal/terapia , Idoso , Canal Anal/fisiopatologia , Incontinência Fecal/fisiopatologia , Feminino , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Fecal incontinence (FI), the involuntary passage of stool, is common and can markedly impair the quality of life. Among patients who fail initial options (pads or protective devices, bowel modifying agents, and pelvic floor exercises), the options are pelvic floor biofeedback (BIO), perianal injection with bulking agents (INJ), and sacral nerve electrical stimulation (SNS), which have not been subjected to head-to-head comparisons. This study will compare the safety and efficacy of BIO and INJ for managing FI. The impact of these approaches on quality-of-life and psychological distress, cost effectiveness, and predictors of response to therapy will also be evaluated. Six centers in the United States will enroll approximately 285 patients with moderate to severe FI. Patients who have 4 or more FI episodes over 2 weeks proceed to a 4-week trial of enhanced medical management (EMM) (ie, education, bowel management, and pelvic floor exercises). Thereafter, 194 non-responders as defined by a less than 75% reduction in the frequency of FI will be randomized to BIO or INJ. Three months later, the efficacy, safety, and cost of therapy will be assessed; non-responders will be invited to choose to add the other treatment or SNS for the remainder of the study. Early EMM responders will be re-evaluated 3 months later and non-responders randomized to BIO or INJ. Standardized, and where appropriate validated approaches will be used for study procedures, which will be performed by trained personnel. Prospectively collected data on care costs and resource utilization will be used for cost effectiveness analyses.
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Incontinência Fecal , Biorretroalimentação Psicológica , Análise Custo-Benefício , Terapia por Exercício , Incontinência Fecal/terapia , Humanos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
Dysbiosis is implicated by many studies in the pathogenesis of Parkinson's disease (PD). Advances in sequencing technology and computing have resulted in confounding data regarding pathogenic bacterial profiles in conditions such as PD. Changes in the microbiome with reductions in short-chain fatty acid (SCFA)-producing bacteria and increases in endotoxin-producing bacteria likely contribute to the pathogenesis of PD. GPR109A, a G-protein coupled receptor found on the surface of the intestinal epithelium and immune cells, plays a key role in controlling intestinal permeability and the inflammatory cascade. The absence of GPR109A receptors is associated with decreased concentration of tight junction proteins, leading to increased intestinal permeability and susceptibility to inflammation. In inflammatory states, butyrate acts via GPR109A to increase concentrations of tight junction proteins and improve intestinal permeability. Niacin deficiency is exacerbated in PD by dopaminergic medications. Niacin supplementation has been shown to shift macrophage polarization from pro-inflammatory to an anti-inflammatory profile. Niacin and butyrate, promising nutrients and unique ligands for the G protein-coupled receptor GPR109A, are reviewed in this paper in detail.
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Butiratos/uso terapêutico , Suplementos Nutricionais , Disbiose/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Niacina/uso terapêutico , Doença de Parkinson/tratamento farmacológico , Animais , Butiratos/metabolismo , Disbiose/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Mucosa Intestinal/metabolismo , Niacina/metabolismo , Doença de Parkinson/metabolismo , Permeabilidade/efeitos dos fármacosRESUMO
INTRODUCTION: Non-coeliac gluten/wheat sensitivity (NCG/WS) is a syndrome characterized by intestinal and extra-intestinal symptoms occurring a few hours or days after the ingestion of gluten and wheat proteins in patients testing negative for coeliac disease and wheat allergy. Areas covered: The present review deals with recent scientific acquisitions of this gluten-related syndrome, including pathogenetic mechanisms, clinical picture, symptom score, biomarkers and double-blind placebo-controlled trial for diagnosis, and treatment. The methodology used was a literature search on NCG/WS using Medline and Premedline from 1970 to August 2016. Expert commentary: We discussed the pathogenesis of symptom generation and altered gut physiology in NCG/WS. Possible mechanisms include innate and adaptive immune activation, impaired intestinal epithelial barrier and changes in gut microbiome. These interlinked factors may be exploited for their clinical relevance as possible biomarkers. A systemic immune response to microbial and wheat antigens, together with intestinal cell damage, occurs in patients with NCG/WS. Due to the lack of established biomarkers, it is mandatory to validate the diagnosis of the syndrome by means of a well-defined work-up involving dietary challenge. Finally, dietary and other therapeutic indications have been thoroughly reviewed.