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BACKGROUND AND AIMS: Archaea constitute one of the main three domains of the tree of life, distinct from eukaryotes and bacteria. Excessive luminal loads of methanogenic archaea (intestinal methanogen overgrowth, IMO) have been implicated in the pathophysiology of various diseases, including constipation. To elucidate the phenotypical presentation of IMO, we performed a systematic review and meta-analysis of the prevalence and severity of gastrointestinal (GI) symptoms in subjects with IMO as compared to subjects without IMO. METHODS: Electronic databases, including OVID MEDLINE and Cochrane Database from inception until September 2023, were systematically searched. Prevalence rates, odds ratios (ORs), standardized mean difference (SMD) and 95% confidence intervals (CIs) of symptoms were calculated. RESULTS: Nineteen studies were included (1293 patients with IMO and 3208 controls). IMO patients exhibited various GI symptoms, including bloating (78%), constipation (51%), diarrhea (33%), abdominal pain (65%), nausea (30%), and flatulence (56%). Patients with IMO had a significantly higher prevalence of constipation as compared to controls (47% vs. 38%, OR 2.04, 95% CI 1.48-2.83, p<0.0001) along with lower prevalence of diarrhea (37% vs. 52%, OR 0.58, 95% CI 0.37-0.90, p=0.01) and nausea (32% vs. 45%, OR 0.75, 95% CI 0.60-0.94, p=0.01). Patients with IMO had higher severity of constipation (SMD 0.77; 95% CI 0.11-1.43, p=0.02) and lower severity of diarrhea (SMD -0.71, 95% CI -1.39, -0.03, p=0.04). Significant heterogeneity was detected. CONCLUSION: Patients with IMO exhibit a higher rate and severity of constipation along with lower rate and severity of diarrhea. The distinct phenotype of IMO patients should be incorporated in patient-reported outcome measures and further correlated with mechanistic microbiome studies.
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INTRODUCTION: A 2-hour breath test is the gold standard for diagnosing intestinal methanogen overgrowth (IMO). This method can be cumbersome especially if used repetitively to monitor treatment response. Therefore, we aimed to assess the reliability of a fasting single methane measurement (SMM) in diagnosing IMO and its utility as a biomarker to monitor treatment response in subjects with IMO. METHODS: First, we calculated the test characteristics of SMM compared with lactulose and glucose breath test in 2 large-scale retrospective cohorts. Second, the symptomology associated with SMM using various cutoffs was analyzed. Third, in a double-blind randomized control trial, the temporal stability of SMM levels in subjects taking placebo was analyzed. Fourth, stool Methanobrevibacter smithii loads were quantified using quantitative polymerase chain reaction and compared with SMM levels. Last, the change in SMM over time during antibiotic therapy was analyzed. RESULTS: Using the cutoff of SMM ≥10 ppm, SMM had a sensitivity of 86.4% and specificity of 100% for diagnosing IMO on the glucose and lactulose breath tests and was associated with constipation (5.65 ± 3.47 vs 4.32 ± 3.62, P = 0.008). SMM remained stable for 14 weeks without treatment (P = 0.45), and antibiotics lead to a decrease in SMM after 2 days (P < 0.0001). SMM was positively associate with stool M. smithii load (R = 0.65, P < 0.0001). DISCUSSION: Fasting SMM ≥10 ppm seems to accurately diagnose IMO, is associated with constipation, and correlates with stool M. smithii. SMM seems to be stable without treatment and decreases after antibiotics. SMM may be a useful test to diagnose IMO and monitor treatment response.
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Síndrome do Intestino Irritável , Lactulose , Antibacterianos/uso terapêutico , Testes Respiratórios , Constipação Intestinal/tratamento farmacológico , Jejum , Glucose , Humanos , Síndrome do Intestino Irritável/complicações , Lactulose/uso terapêutico , Metano/análise , Reprodutibilidade dos Testes , Estudos RetrospectivosRESUMO
BACKGROUND: Total proctocolectomy with ileal pouch-anal anastomosis has become the standard procedure for patients with medically refractory ulcerative colitis, although a subset will develop de novo Crohn's disease. OBJECTIVE: In this study, we investigated the association of preoperative C-reactive protein levels with the development of de novo Crohn's disease after ileal pouch-anal anastomosis. DESIGN: A prospectively maintained database of patients undergoing ileal pouch-anal anastomosis was reviewed. PATIENTS: Preoperative C-reactive protein levels were compared between patients who developed de novo Crohn's disease and those who did not. De novo Crohn's disease was defined as small-bowel inflammation proximal to the ileal pouch or perianal disease identified more than 3 months after ileostomy closure. To minimize the heterogeneity of the timing of preoperative C-reactive protein measurement and the severity of ulcerative colitis, only hospitalized patients who had proctocolectomy for severe ulcerative colitis were included in the study. MAIN OUTCOME MEASURES: Development of de novo Crohn's disease was analyzed. RESULTS: Of 105 patients, 23 (22%) developed de novo Crohn's disease. Having C-reactive protein in the third tertile significantly increased the risk of developing de novo Crohn's disease (HR 3.44, 95% CI 1.10- 10.70, p = 0.03) compared to in the first tertile. In a multivariable model, a C-reactive protein in the third or second tertile vs the first tertile and younger age was associated with the development of de novo Crohn's disease. LIMITATIONS: Limited to only hospitalized patients with severe ulcerative colitis. CONCLUSIONS: In hospitalized patients undergoing ileal pouch-anal anastomosis for medically refractory ulcerative colitis, higher preoperative C-reactive protein levels appear to increase the risk of developing de novo Crohn's disease. See Video Abstract at http://links.lww.com/DCR/B750.LA MAGNITUD DE LA ELEVACIÓN PREOPERATORIA DE LA PROTEÍNA C REACTIVA SE ASOCIA CON APARICIÓN DE UNA ENFERMEDAD DE CROHN DE NOVO DESPUÉS DE UNA ANASTOMOSIS DE BOLSA ILEAL AL ANO EN PACIENTES CON COLITIS SEVERAANTECEDENTES:La proctocolectomía total con anastomosis bolsa ileal-anal se ha convertido en el procedimiento estándar para los pacientes con colitis ulcerativa refractaria al tratamiento médico, aunque un subgrupo desarrollará una enfermedad de Crohn de novo.OBJETIVO:En este estudio investigamos la asociación de los niveles de proteína C reactiva preoperatoria con el desarrollo de la enfermedad de Crohn de novo, después de la anastomosis bolsa ileal-anal.DISEÑO:Se revisó una base de datos recolectada en forma prospectiva, de pacientes sometidos a anastomosis bolsa ileal-anal.PACIENTES:Se compararon los niveles de proteína C reactiva preoperatoria entre los pacientes que desarrollaron la enfermedad de Crohn de novo y los que no la desarrollaron. La enfermedad de Crohn de novo se definió como una inflamación del intestino delgado proximal a la bolsa ileal o una enfermedad perianal identificada más de 3 meses después del cierre de la ileostomía. Para minimizar la heterogeneidad del momento de la medición de la proteína C reactiva preoperatoria y la gravedad de la colitis ulcerativa, solo se incluyeron en el estudio los pacientes hospitalizados que se sometieron a una proctocolectomía por colitis ulcerativa grave.PRINCIPALES MEDIDAS DE RESULTADO:se analizó el desarrollo de la enfermedad de Crohn de novo.RESULTADOS:De 105 pacientes, 23 (22%) desarrollaron enfermedad de Crohn de novo. Tener una proteína C reactiva en el tercer tercil aumentó significativamente el riesgo de desarrollar la enfermedad de Crohn de novo (HR 3,44, IC del 95%: 1,10-10,70, p = 0,03) en comparación con el primer tercil. En un modelo multivariable, una proteína C reactiva en el tercer o segundo tercil frente al primer tercil y una edad más joven se asoció con el desarrollo de la enfermedad de Crohn de novo.LIMITACIONES:Limitado solo a pacientes hospitalizados con colitis ulcerativa grave.CONCLUSIONES:En pacientes hospitalizados sometidos a anastomosis bolsa ileal-anal por colitis ulcerativa refractaria al tratamiento médico, niveles más elevados de proteína C reactiva preoperatoria parecen aumentar el riesgo de desarrollar enfermedad de Crohn de novo. Consulte Video Resumen en http://links.lww.com/DCR/B750. (Traducción-Eduardo Londoño-Schimmer).
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Proteína C-Reativa/análise , Colite Ulcerativa , Doença de Crohn , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Adulto , Biomarcadores/sangue , Colite Ulcerativa/sangue , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/cirurgia , Doença de Crohn/diagnóstico , Doença de Crohn/epidemiologia , Doença de Crohn/etiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Valor Preditivo dos Testes , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Prognóstico , Índice de Gravidade de Doença , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: In humans, methane (CH4) is exclusively produced by the intestinal microbiota and has been implicated in several conditions including cardiovascular disease. After microbial production of CH4 in the gut, it steadily crosses into the systemic circulation and reaches the lungs where it can be detected in the exhaled breath, as a surrogate measure for intestinal CH4 production. Recent reports have shown an association between CH4 and vagal dysfunction as well as the inhibition of CH4 activity on ileal contractions with atropine, suggesting its action on the parasympathetic nervous system. Given these findings, we hypothesized that CH4 may be affecting resting heart rate (HR) based on the potential effect of CH4 on the vagus nerve. OBJECTIVES: Given its possible role in the parasympathetic nervous system, we aimed to study the relationship between breath CH4 and resting HR in humans. Additionally, we performed a longitudinal study analyzing the change in HR and its association with breath CH4 over time. METHODS: First, we reviewed 1,126 subjects and compared HR in subjects with detectable and undetectable breath CH4. Second, we performed a post hoc analysis of a randomized control trial to compare the change in HR for those who had an increase in breath CH4 versus those that had a decrease in breath CH4 over 14 weeks. Last, we assessed whether a larger decrease in CH4 is associated with a larger increase in HR over time. RESULTS: In the retrospective cohort, subjects with detectable CH4 had a lower HR compared to those with undetectable CH4 (73.0 ± 0.83 vs. 76.0 ± 0.44 beats/min, p = 0.01). In the post hoc analysis, a decrease in CH4 over time was associated with an increase in HR (median ∆ = 6.5 ± 8.32 beats/min, p = 0.0006). Last, we demonstrated a biological gradient whereby a larger drop in CH4 was associated with a greater increase in HR (R = -0.31, p = 0.03). CONCLUSION: Our findings suggest a potential role for the microbiome (and specifically CH4 from methanogens) to regulate HR. Considering these findings, mechanistic studies are warranted to further investigate this potential novel microbiome-neurocardiac axis.
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Testes Respiratórios , Metano , Frequência Cardíaca , Humanos , Estudos Longitudinais , Estudos RetrospectivosRESUMO
BACKGROUND & AIMS: Although dysphagia is common, there is limited information about the prevalence and burden of illness of dysphagia in the United States. We performed a population-based survey of more than 31,000 adults to evaluate the epidemiology, clinical characteristics, and health care-seeking behavior of individuals with dysphagia. METHODS: We performed a cross-sectional analysis of adults in the United States who completed an online, self-administered health survey from April 4 through April 19, 2018. All respondents were asked which of the following symptoms they had ever experienced (presented in random order): dysphagia, abdominal pain, bloating, bowel incontinence, constipation, diarrhea, heartburn/reflux, nausea/vomiting, or none of the above. Only respondents who selected dysphagia continued the remaining survey, which included questions about dysphagia severity, use of compensatory maneuvers, health care seeking, and esophageal comorbidities. We used multivariable regression methods to adjust for confounding. RESULTS: Of 31,129 individuals who participated in the survey, 4998 respondents (16.1%) reported experiencing dysphagia; 92.3% of these had symptoms in the previous week. We found that 16.3% of respondents described their dysphagia over the previous 7 days as either quite a bit or very severe. Drinking liquids to help with dysphagia (86.0%) and taking longer to finish eating (76.5%) were the most common compensatory maneuvers. Overall, 51.1% of individuals sought care for their difficulty swallowing; older age, male sex, having a usual source of care and insurance, having comorbidities, and more severe dysphagia symptoms increased the odds for seeking care (P < .05). The most commonly reported esophageal comorbidities were gastroesophageal reflux disease (30.9%), eosinophilic esophagitis (8.0%), and esophageal stricture (4.5%). CONCLUSIONS: In a large population-based survey, we found that dysphagia is common; 1 of 6 adults reported experiencing difficulty swallowing. However, half of individuals have not discussed their symptoms with a clinician and many could have treatable disorders.
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Transtornos de Deglutição , Refluxo Gastroesofágico , Adulto , Idoso , Estudos Transversais , Transtornos de Deglutição/epidemiologia , Azia , Humanos , Masculino , Prevalência , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Most patients with IBD experience pain, especially during acute disease exacerbations. Opioid use continues to be more prevalent in IBD than any other chronic gastrointestinal condition, and the majority of IBD patients consume narcotics during hospitalization despite the risks of infection and death. METHODS: We performed a retrospective review of 57 subjects aimed at quantifying pain and opiate consumption for IBD-related admissions over a 3-month period. For each patient, the average and maximum of each day's pain scores were used to measure changes in pain from admission to discharge using mixed model regression, with opiate use as a time-dependent covariate. RESULTS: The daily average pain score over the entire hospitalization was 4.23 ± 2.09, and the maximum pain score was 8.28 ± 1.75. Among opioid users (n = 51), the daily average pain score was 4.65 ± 2.16 and the maximum pain score was 7.53 ± 2.56. Across all cases from admission to discharge, there was less than a 1-point change in daily average pain (- 0.96 ± 2.03, p = 0.0009), and no change in maximum pain (- 0.89 ± 3.59, p = 0.0671). Opioid users, a subset of the overall cohort, had a similar less than one-point drop in daily average pain (- 0.94 ± - 0.29, p = 0.0024) and no change in daily maximum pain scores (- 0.81 ± - 0.47, p = 0.0914). Patients on average used 20 ± 25 mg morphine equivalents per day. Opioid-naïve patients used similar doses to those who used opioids prior to admission (PTA). Almost half of all cases (47%) were discharged with an opioid prescription, the majority (71%) of whom were not on opioids PTA. CONCLUSIONS: Pain in IBD is not well controlled through hospitalization, with less than a 1-point change from admission to discharge, despite significant opioid consumption. Alternative analgesic methods should be explored, given the significant impact of narcotics on long-term outcomes including mortality and quality of life.
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Analgésicos Opioides/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Dor/tratamento farmacológico , Dor/etiologia , Aceitação pelo Paciente de Cuidados de Saúde , Adulto , Analgésicos Opioides/administração & dosagem , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is a rare, idiopathic biliary disease often with an insidious onset, variable disease course, and premature death related to benign and malignant PSC-related sequelae. This review aims to discuss the epidemiology, clinical variants, and natural history of PSC, incorporating data from recent population-based studies. RECENT FINDINGS: PSC naturally leads to cirrhosis, cholangiocarcinoma, other hepatobiliary malignancies, dominant strictures, hepatic osteodystrophy, and bacterial cholangitis. The incidence of PSC appears to be increasing, the reasons for which are unclear. The time from diagnosis to liver transplant appears to be longer in more recent studies compared with earlier studies, suggesting a better overall prognosis than previously believed. In addition, with an increasing number of patients undergoing liver transplantation for PSC, the frequency of death because of liver failure has decreased, whereas cancer-related deaths have increased among patients with PSC. SUMMARY: PSC is a heterogeneous disease with a variety of clinical outcomes, both fatal and nonfatal. The progression of liver fibrosis in an individual patient is difficult to predict and may vary from a relatively benign, nonprogressive form to a rapidly progressive form with the need for liver transplantation.
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Colangite Esclerosante/complicações , Infecções Bacterianas/complicações , Neoplasias dos Ductos Biliares/etiologia , Doenças Ósseas Metabólicas/etiologia , Colangiocarcinoma/etiologia , Colangite Esclerosante/diagnóstico por imagem , Colangite Esclerosante/epidemiologia , Colestase/etiologia , Progressão da Doença , Humanos , Cirrose Hepática/etiologia , PrognósticoRESUMO
Background/Aims: We performed a systematic review and meta-analysis evaluating the symptomatic response rate to antibiotics in patients with small intestinal bacterial overgrowth (SIBO). Similarly, we performed a meta-analysis on the symptomatic response to antibiotics in irritable bowel syndrome (IBS) patients with and without SIBO. Methods: MEDLINE, EMBASE, Web of Science, and Cochrane databases were searched from inception to March 2021. Randomized controlled trials and prospective studies reporting dichotomous outcomes were included. Results: There were 6 studies included in the first meta-analysis comparing the efficacy of antibiotics to placebo or no antibiotic. This included 196 patients, of whom 101 received antibiotics and 95 received placebo or no antibiotics. Significantly more patients improved with antibiotics (relative risk [95% CI] = 2.46 [1.33-4.55], P = 0.004). There were 4 studies included in the analysis comparing symptomatic response rates in IBS patients with or without SIBO with 266 IBS patients, of whom 172 had SIBO and 94 did not. The pooled response rate for symptomatic response was 51.2% in the SIBO group vs 23.4% in the no SIBO group, respectively. Significantly more IBS patients with SIBO responded to antibiotics compared to those without SIBO (relative risk [95% CI] = 2.07 [1.40-3.08], P = 0.0003). Conclusions: Antibiotics appear to be efficacious in treating SIBO, although small sample sizes and poor data quality limit this interpretation. Symptomatic response rates also appear to be higher in IBS patients with SIBO. This may be the first example of precision medicine in IBS as opposed to our current empiric treatment approach. Large-multicenter studies are needed to verify the results.
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INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis have limited efficacy and it is difficult to predict which patients will respond. In this study, we implemented a machine-learning model to predict the response to prokinetics and/or neuromodulators in patients with gastroparesis-like symptoms. METHODS: Subjects with suspected gastroparesis underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule (WMC) and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their Gastroparesis Cardinal Symptom Index (GCSI) at 6 months decreased by ≥1 from baseline. A machine-learning model was trained using lasso regression, ridge regression or random forest. Five-fold cross-validation was used to train the models and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were non-responders. A ridge regression model with the variables: BMI, Infectious prodrome, delayed GES, no diabetes (BIDnD), had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with GET, duodenal MI, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with gastroparesis-like symptoms.
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INTRODUCTION: While high-resolution manometry (HRM) is widely accepted as a safe procedure, no study has assessed the safety profile of HRM in clinical practice. This study aimed to determine the safety and tolerability of HRM and to investigate potential determinants of intolerability. METHODS: We obtained HRM procedure reports, demographics, and clinical data (2005-2022) at a tertiary center using electronic chart review. Our primary outcome was HRM tolerability. Multivariable regression was performed to identify associations between the outcome and covariates including age, sex, race, and comorbidities. RESULTS: A total of 5,107 patients (60.3% female) were included. Of them, 5,050 patients (98.9%) tolerated HRM well and 57 patients (1.1%) did not. Age had a statistically significant effect on tolerance: those younger than 18 years had more than a 5-fold increase in not tolerating HRM compared with those aged 18-79 years (5.77% vs 0.99%; odds ratio [OR] = 5.44, 95% confidence interval [CI] 1.60-18.45; P = 0.007), and those aged 80 years or older were also more likely to terminate HRM (2.43% vs 0.99%; OR = 2.56, 95% CI 1.13-5.76; P = 0.024). While prior foregut surgery had a significant effect on tolerance (OR = 8.06, 95% CI 2.29-28.39; P = 0.001), other factors of race, sex, body mass index, and psychological or cognitive disorders had no significant impact. No serious complications were identified. DISCUSSION: HRM is safe and well-tolerated with approximately 1 in every 100 patients being unable to tolerate HRM. Intolerance was more commonly seen in children and seniors due to minor symptoms of discomfort without serious complications. These data points are crucial to counsel patients in whom HRM is being considered.
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Transtornos Cognitivos , Esôfago , Humanos , Adulto , Criança , Feminino , Masculino , Manometria/métodos , Índice de Massa Corporal , Transtornos Cognitivos/etiologiaRESUMO
Most hospitalized patients with inflammatory bowel disease (IBD) experience pain. Despite the known risks associated with opioids in IBD including risk for misuse, overdose, infection, readmission, and even death, opioid use is more prevalent in IBD than any other chronic gastrointestinal condition. Most hospitalized IBD patients receive opioids; however, opioids have not been shown to improve pain during hospitalization. We conducted a randomized controlled trial in hospitalized patients with IBD to evaluate the impact of a proactive opioid-sparing analgesic protocol. Wearable devices measured activity and sleep throughout their hospitalization. Chronic opioid users, post-operative, and pregnant patients were excluded. The primary endpoint was a change in pain scores from admission to discharge. Secondary endpoints included opioid use, functional activity, sleep duration and quality, and length of stay. Of 329 adults with IBD evaluated for eligibility, 33 were enrolled and randomized to the intervention or usual care. Both the intervention and control group demonstrated significant decreases in pain scores from admission to discharge (- 2.6 ± 2.6 vs. - 3.0 ± 3.2). Those randomized to the intervention tended to have lower pain scores than the control group regardless of hospital day (3.02 ± 0.90 vs. 4.29 ± 0.81, p = 0.059), used significantly fewer opioids (daily MME 11.8 ± 15.3 vs. 30.9 ± 42.2, p = 0.027), and had a significantly higher step count by Day 4 (2330 ± 1709 vs. 1050 ± 1214; p = 0.014). There were no differences in sleep duration, sleep quality, readmission, or length-of-stay between the two groups. A proactive analgesic protocol does not result in worsening pain but does significantly reduce opioid-use in hospitalized IBD patients.Clinical trial registration number: NCT03798405 (Registered 10/01/2019).
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Doenças Inflamatórias Intestinais , Transtornos Relacionados ao Uso de Opioides , Adulto , Gravidez , Feminino , Humanos , Analgésicos Opioides/efeitos adversos , Analgésicos/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Dor/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: proving causality between an exposure and outcome can be difficult in humans. Here, we utilize the Bradford Hill (BH) criteria to summarize the causal relationship between Campylobacter infection and the development of Irritable Bowel Syndrome (IBS). METHODS: we utilized the BH criteria to assess the strength, consistency, specificity, temporality, biological gradient, plausibility, coherence, experiment, and analogy of the current evidence linking Campylobacter to IBS. Through a consensus amongst all authors, the confidence of each criterion was graded as high, moderate, low, or very low. RESULTS: a total of four criteria (strength, temporality, plausibility, and analogy) were graded as high; four criteria (consistency, biological gradient, coherence, and experiment) were graded as moderate; and one criterion (specificity) was graded as low. Large-scale epidemiological studies report a risk ratio of 2.7-5.6 for developing IBS after campylobacter. In rodent models, Campylobacter jejuni 81-176 can cause loose stool months after the infection is cleared and share common pathophysiology as IBS patients such as elevated intestinal TLR-4 and IL-8, antibodies to CdtB and vinculin, increased intraepithelial lymphocytes, and small intestinal bacterial overgrowth. CONCLUSIONS: Campylobacter infection appear to cause IBS in a subset of patients. This may hold implication in risk factor identification, public health policy, and possibly treatment.
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Infecções por Campylobacter , Síndrome do Intestino Irritável , Infecções por Campylobacter/complicações , Diarreia , Humanos , Síndrome do Intestino Irritável/etiologia , Razão de Chances , Fatores de RiscoRESUMO
INTRODUCTION: Our previous preclinical experiments show that under specific and monitored conditions, ultraviolet A (UVA) exposure reduces certain bacteria, fungi, and viruses including coronavirus-229E without harming mammalian columnar epithelial cells. The goal of this study was to evaluate the safety and effects of narrow-band UVA therapy administered by a novel device via endotracheal tube in critically ill subjects with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Newly intubated, mechanically ventilated adults with SARS-CoV-2 infection and an endotracheal tube size of at least 7.50 mm were eligible for inclusion in the study. Subjects were treated with UVA for 20 min daily for 5 days and followed for 30 days. RESULTS: Five subjects were enrolled (mean age 56.60 years, three male). At baseline, all subjects scored 9/10 on the World Health Organization (WHO) clinical severity scale (10 = death), with predicted mortality ranging from 21% to 95%. Average endotracheal viral load significantly reduced from baseline to day 5 (- 2.41 log; range - 1.16 to - 4.54; Friedman p = 0.002) and day 6 (- 3.20; range - 1.20 to - 6.77; Friedman p < 0.001). There were no treatment-emergent adverse events, with no changes in oxygenation or hemodynamics during the 20-min treatments. One subject died 17 days after enrollment due to intracranial hemorrhagic complications of anticoagulation while receiving extracorporeal membrane oxygenation. The remaining subjects clinically improved and scored 2, 4, 5, and 7 on the WHO scale at day 30. In these subjects, clinical improvement correlated with reduction of viral load (Spearman's rho = 1, p < 0.001). CONCLUSIONS: In this first-in-human study, endotracheal narrow-band UVA therapy, under specific and monitored settings, appears to be safe and associated with a reduction in respiratory SARS-CoV-2 viral burden over the treatment period. UVA therapy may provide a novel approach in the fight against COVID-19. CLINICAL TRIAL NUMBER: NCT04572399.
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COVID-19 , SARS-CoV-2 , Adulto , Estado Terminal , Humanos , Masculino , Pessoa de Meia-Idade , Carga ViralRESUMO
Small intestinal bacterial overgrowth (SIBO) is one manifestation of gut microbiome dysbiosis and is highly prevalent in IBS (Irritable Bowel Syndrome). SIBO can be diagnosed either by a small bowel aspirate culture showing ≥103 colony-forming units (CFU) per mL of aspirate, or a positive hydrogen lactulose or glucose breath test. Numerous pathogenic organisms have been shown to be increased in subjects with SIBO and IBS, including but not limited to Enterococcus, Escherichia coli, and Klebsiella. In addition, Methanobrevibacter smithii, the causal organism in a positive methane breath test, has been linked to constipation predominant irritable bowel syndrome (IBS-C). As M. smithii is an archaeon and can overgrow in areas outside of the small intestine, it was recently proposed that the term intestinal methanogen overgrowth (IMO) is more appropriate for the overgrowth of these organisms. Due to gut microbiome dysbiosis, patients with IBS may have increased intestinal permeability, dysmotility, chronic inflammation, autoimmunity, decreased absorption of bile salts, and even altered enteral and central neuronal activity. As a consequence, SIBO and IBS share a myriad of symptoms including abdominal pain, distention, diarrhea, and bloating. Furthermore, gut microbiome dysbiosis may be associated with select neuropsychological symptoms, although more research is needed to confirm this connection. This review will focus on the role of the gut microbiome and SIBO in IBS, as well as novel innovations that may help better characterize intestinal overgrowth and microbial dysbiosis.
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Irritable bowel syndrome (IBS) is a common disorder requiring complex, multidisciplinary management. Antidepressants are commonly used and recommended in guidelines for the treatment of patients with IBS. We assessed randomized controlled trials (RCTs) on antidepressants in patients with IBS, with specific attention to study design and data quality/reporting characteristics. Following a comprehensive search, data and RCT characteristics were systematically summarized. Fragility index, representing the number of positive "events" that the study relies on for its significance, was calculated. Eighteen RCTs were included. Overall, tricyclic antidepressants (TCAs), but not selective serotonin reuptake inhibitors (SSRIs), appeared to be efficacious in IBS. Eight studies reported on adverse events (AEs), which were significantly greater in patients receiving antidepressants versus placebo. The median (mean) fragility index of TCA trials was 0 (1.5). RCTs with positive results had significantly lower placebo rates (20.8%) versus negative studies (45.7%; p < 0.0001). RCTs exhibited limitations related to study design (sample size and blinding), data analysis (outcomes and placebo response), and data reporting (selective reporting of AEs and publication bias). Careful consideration of limitations of RCTs on antidepressants in IBS is warranted to formulate a safe and beneficial treatment regimen for patients with IBS.