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BACKGROUND & AIMS: Clostridioides difficile infection (CDI) is associated with high mortality. Fecal microbiota transplantation (FMT) is an established treatment for recurrent CDI, but its use for first or second CDI remains experimental. We aimed to investigate the effectiveness of FMT for first or second CDI in a real-world clinical setting. METHODS: This multi-site Danish cohort study included patients with first or second CDI treated with FMT from June 2019 to February 2023. The primary outcome was cure of C. difficile-associated diarrhea (CDAD) 8 weeks after the last FMT treatment. Secondary outcomes included CDAD cure 1 and 8 weeks after the first FMT treatment and 90-day mortality following positive C. difficile test. RESULTS: We included 467 patients, with 187 (40%) having their first CDI. The median patient age was 73 years (interquartile range [IQR], 58-82 years). Notably, 167 (36%) had antibiotic-refractory CDI, 262 (56%) had severe CDI, and 89 (19%) suffered from fulminant CDI. Following the first FMT treatment, cure of CDAD was achieved in 353 patients (76%; 95% confidence interval [CI], 71%-79%) at week 1. At week 8, 255 patients (55%; 95% CI, 50%-59%) maintained sustained effect. In patients without initial effect, repeated FMT treatments led to an overall cure of CDAD in 367 patients (79%; 95% CI, 75%-82%). The 90-day mortality was 10% (95% CI, 8%-14%). CONCLUSION: Repeated FMT treatments demonstrate high effectiveness in managing patients with first or second CDI. Forwarding FMT in CDI treatment guidelines could improve patient survival. CLINICALTRIALS: gov, Number: NCT03712722.
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The prevalence and disease burden of chronic inflammatory diseases (CIDs) are predicted to rise. Patients are commonly treated with biological agents, but the individual treatment responses vary, warranting further research into optimizing treatment strategies. This study aimed to compare the clinical treatment responses in patients with CIDs initiating biologic therapy based on smoking status, a notorious risk factor in CIDs. In this multicentre cohort study including 233 patients with a diagnosis of Crohn's disease, ulcerative colitis, rheumatoid arthritis, axial spondyloarthritis, psoriatic arthritis or psoriasis initiating biologic therapy, we compared treatment response rates after 14 to 16 weeks and secondary outcomes between smokers and non-smokers. We evaluated the contrast between groups using logistic regression models: (i) a "crude" model, only adjusted for the CID type, and (ii) an adjusted model (including sex and age). Among the 205 patients eligible for this study, 53 (26%) were smokers. The treatment response rate among smokers (n = 23 [43%]) was lower compared to the non-smoking CID population (n = 92 [61%]), corresponding to a "crude" OR of 0.51 (95% CI: [0.26;1.01]) while adjusting for sex and age resulted in consistent findings: 0.51 [0.26;1.02]. The contrast was apparently most prominent among the 38 RA patients, with significantly lower treatment response rates for smokers in both the "crude" and adjusted models (adjusted OR 0.13, [0.02;0.81]). Despite a significant risk of residual confounding, patients with CIDs (rheumatoid arthritis in particular) should be informed that smoking probably lowers the odds of responding sufficiently to biological therapy. Registration: Clinical.Trials.gov NCT03173144.
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Artrite Reumatoide , Produtos Biológicos , Fumar , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Estudos Prospectivos , Fumar/efeitos adversos , Produtos Biológicos/uso terapêutico , Resultado do Tratamento , Artrite Reumatoide/tratamento farmacológico , Psoríase/tratamento farmacológico , Colite Ulcerativa/tratamento farmacológico , Doença Crônica , Doença de Crohn/tratamento farmacológico , Estudos de Coortes , Artrite Psoriásica/tratamento farmacológico , Idoso , InflamaçãoRESUMO
OBJECTIVE: Chronic diarrhea affects approximately 5% of the population. Opioids inhibit gastrointestinal motility, and opium tincture has shown anti-propulsive effects in healthy, but no controlled studies of its clinical efficacy exist. We aimed to investigate the anti-propulsive and central nervous system (CNS) effects of opium tincture in patients with chronic diarrhea. MATERIALS AND METHODS: The study was a randomized, double-blinded, placebo-controlled, cross-over trial in subjects with chronic diarrhea refractory to standard treatment. Participants received opium tincture or placebo during two intervention periods, each lasting seven days. Bowel movements were recorded daily, and gastrointestinal transit time was investigated with the wireless motility capsule system. Gastrointestinal symptoms, health-related quality of life, and CNS effects (pupil size, reaction time, memory, and general cognition) were also investigated, along with signs of addiction. RESULTS: Eleven subjects (mean age: 45 ± 17 years, 46% males) with a median of 4.7 daily bowel movements were included. The number of daily bowel movements was reduced during opium tincture treatment to 2.3 (p = 0.045), but not placebo (3.0, p = 0.09). Opium tincture prolonged the colonic transit time compared to placebo (17 h vs. 12 h, p < 0.001). In both treatment arms, there were no changes in self-reported gastrointestinal symptoms, health-related quality of life, or CNS effects, and no indication of addiction was present. CONCLUSION: Opium tincture induced anti-propulsive effects in patients with chronic diarrhea refractory to standard treatment. This indicates that opium tincture is a relevant treatment strategy for selected patients with chronic diarrhea. Moreover, no evidence of opioid-induced sedation or addiction was found.Trial Registration Number: NCT05690321 (registered 2023-01-10).
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Estudos Cross-Over , Diarreia , Qualidade de Vida , Humanos , Diarreia/tratamento farmacológico , Masculino , Feminino , Pessoa de Meia-Idade , Método Duplo-Cego , Adulto , Doença Crônica , Ópio/uso terapêutico , Motilidade Gastrointestinal/efeitos dos fármacos , Trânsito Gastrointestinal/efeitos dos fármacos , Analgésicos Opioides/uso terapêutico , Idoso , Resultado do Tratamento , Defecação/efeitos dos fármacosRESUMO
BACKGROUND: Faecal microbiota transplantation (FMT) has mainly been studied in quantitative research to investigate effect rates. However, there is a lack of qualitative studies to explore patient perspectives. AIM: To explore perceptions of quality of life in older patients with Clostridioides difficile infection (CDI) at least 1 week after receiving FMT. METHOD: A qualitative study examining quality of life for patients treated with FMT. FINDINGS: Patients with a permanent or transient treatment effect experienced an increase in quality of life in the physical, psychological and social domains. However, patients who did not respond to the treatment experienced negative impacts on their psychological, physical, and social domains. Although patients found the content unappealing, none had reservations about receiving the treatment. CONCLUSION: This study highlights the importance of considering the psychological, social and physical wellbeing of patients when assessing the efficacy of FMT as a treatment option for patients with CDI. It further emphasises the importance of health professionals identifying patients' individual ways of handling the disease and everyday life to improve their quality of life.
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Infecções por Clostridium , Qualidade de Vida , Humanos , Idoso , Transplante de Microbiota Fecal , Infecções por Clostridium/terapia , Pessoal de Saúde , PacientesRESUMO
BACKGROUND: High doses of oral thiamine improve clinical fatigue scores in patients with quiescent inflammatory bowel disease (IBD) and chronic fatigue. In this study we analysed plasma samples obtained in a randomised clinical trial and aimed compare levels of vitamins B1, B2, B3 and B6, and their related vitamers and metabolites in patients with IBD, with or without chronic fatigue and with or without effect of high dose oral thiamine for chronic fatigue. METHODS: Blood samples from patients with fatigue were drawn prior and after thiamine exposure and only once for patients without fatigue. A wide panel of analysis were done at Bevital AS Lab. RESULTS: Concentration of flavin mononucleotide (FMN) was lower in patients with chronic fatigue compared to patients without fatigue (p = 0.02). Patients with chronic fatigue who reported a positive effect on fatigue after 4 weeks of high dose thiamine treatment had a statistically significantly lower level of riboflavin after thiamine treatment (p = 0.01). CONCLUSION: FMN and Riboflavin were associated with chronic fatigue in patients with quiescent IBD. Levels of other B vitamins and metabolites were not significantly different between the investigated groups or related to effect of the thiamine intervention. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov study identifier NCT036347359. Registered 15 August 2018, https://clinicaltrials.gov/study/NCT03634735?cond=Inflammatory%20Bowel%20Diseases&intr=Thiamine&rank=1.
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Síndrome de Fadiga Crônica , Doenças Inflamatórias Intestinais , Complexo Vitamínico B , Humanos , Complexo Vitamínico B/uso terapêutico , Tiamina/uso terapêutico , Tiamina/análise , Riboflavina/uso terapêutico , Riboflavina/análise , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
Fecal microbiota transplantation (FMT) is known to be highly effective in patients with recurrent Clostridioides difficile infection (rCDI), but its role in patients who also suffer from inflammatory bowel disease (IBD) is unclear. Therefore, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of FMT for the treatment of rCDI in patients with IBD. We searched the available literature until November 22, 2022 to identify studies that included patients with IBD treated with FMT for rCDI, reporting efficacy outcomes after at least 8 weeks of follow-up. The proportional effect of FMT was summarized with a generalized linear mixed-effect model fitting a logistic regression accounting for different intercepts among studies. We identified 15 eligible studies, containing 777 patients. Overall, FMT achieved high cure rates of rCDI, 81% for single FMT, based on all included studies and patients, and 92% for overall FMT, based on nine studies with 354 patients, respectively. We found a significant advantage of overall FMT over single FMT in improving cure rates of rCDI (from 80% to 92%, p = 0.0015). Serious adverse events were observed in 91 patients (12% of the overall population), with the most common being hospitalisation, IBD-related surgery, or IBD flare. In conclusion, in our meta-analysis FMT achieved high cure rates of rCDI in patients with IBD, with a significant advantage of overall FMT over single FMT, similar to data observed in patients without IBD. Our findings support the use of FMT as a treatment for rCDI in patients with IBD.
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Clostridioides difficile , Infecções por Clostridium , Doenças Inflamatórias Intestinais , Humanos , Transplante de Microbiota Fecal/efeitos adversos , Resultado do Tratamento , Recidiva , Doenças Inflamatórias Intestinais/terapia , Doenças Inflamatórias Intestinais/etiologia , Infecções por Clostridium/terapia , Infecções por Clostridium/etiologiaRESUMO
OBJECTIVE: Patients with an ileostomy may experience postoperative electrolyte derangement and dehydration but are presumed to stabilise thereafter. We aimed to investigate the prevalence of sodium depletion in stable outpatients with an ileostomy and applied established methods to estimate their fluid status. METHODS: We invited 178 patients with an ileostomy through a region-wide Quality-of-Life-survey to undergo outpatient evaluation of their sodium and fluid status. The patients delivered urine and blood samples, had bioelectrical impedance analysis performed and answered a questionnaire regarding dietary habits. RESULTS: Out of 178 invitees, 49 patients with an ileostomy were included; 22 patients (45%, 95% CI, 31-59%) had unmeasurably low urinary sodium excretion (<20 mmol/L), indicative of chronic sodium depletion, and 26% (95% CI, 16-41%) had plasma aldosterone levels above the reference value. Patients with unmeasurably low urinary sodium excretion had low estimated glomerular filtration rates (median 76, IQR 63-89, mL/min/1.73m2) and low venous blood plasma CO2 (median 24, IQR 21-26, mmol/L), indicative of chronic renal impairment and metabolic acidosis. Bioelectrical impedance analysis, plasma osmolality, creatinine and sodium values were not informative in determining sodium status in this population. CONCLUSION: A high proportion of patients with an ileostomy may be chronically sodium depleted, indicated by absent urinary sodium excretion, secondary hyperaldosteronism and chronic renal impairment, despite normal standard biochemical tests. Sodium depletion may adversely affect longstanding renal function. Future studies should investigate methods to estimate and monitor fluid status and aim to develop treatments to improve sodium depletion and dehydration in patients with an ileostomy.IMPACT AND PRACTICE RELEVANCE STATEMENTSodium depletion in otherwise healthy persons with an ileostomy was identified in a few publications from the 1980s. The magnitude of the problem has not been demonstrated before. The present study quantifies the degree of sodium depletion and secondary hyperaldosteronism in this group, and the results may help guide clinicians to optimise treatment. Sodium depletion is easily assessed with a urine sample, and sequelae may possibly be avoided if sodium depletion is detected early and treated. This could ultimately help increase the quality of life in patients with an ileostomy.
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Hiperaldosteronismo , Ileostomia , Humanos , Ileostomia/efeitos adversos , Desidratação/etiologia , Pacientes Ambulatoriais , Estudos Transversais , Qualidade de Vida , Sódio/urinaRESUMO
BACKGROUND: Disease-related-malnutrition predicts poor clinical outcomes in elderly patients, and screening is pivotal for identifying patients at nutritional risk. The present study aimed to investigate nutrition screening rates in electronic patient records and validate the scores given. A secondary aim was to investigate whether the proportion of patients at risk differed between patients where screening was documented and those where no screening was documented. METHODS: This cross-sectional observational study was conducted in a Danish university hospital during November 2020. Patients aged 65 years or more admitted to a medical department were included. The Nutrition Risk Screening 2002 (NRS-2002) tool was used to identify patients at nutritional risk, both in routine clinical care, where data were collected retrospectively, and during a validation process in a random patient sample, where data were collected prospectively. RESULTS: In total, 817 patients were admitted for more than 24 h. Of these, an NRS-2002 score was documented in 294 (36%), among whom 177 (60%) were at nutritional risk. In 146 patients where no score was documented, 88 (60%) were at risk. Validation was possible in 91 patients where a record-based score and a validated score were documented. The specificity of the record-based score was 100%, whereas the sensitivity was 75%, indicating that routine screening underestimated nutritional risk (p < 0.001, proportion difference 19%; 95% confidence interval = 10%-28%). CONCLUSIONS: Electronic documentation does not solve issues about compliance with nutritional risk screening. In patients where screening was not documented, the occurrence of nutritional risk was similar, indicating that omission of screening is not related to the score.
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Desnutrição , Avaliação Nutricional , Idoso , Humanos , Estudos Transversais , Estudos Retrospectivos , Estado Nutricional , Desnutrição/diagnóstico , Desnutrição/epidemiologia , Desnutrição/prevenção & controle , Hospitais Universitários , DinamarcaRESUMO
OBJECTIVE AND AIMS: Fatigue is common in inflammatory bowel disease (IBD). In a RCT we demonstrated reductions in fatigue after 4 weeks' treatment with high-dose oral thiamine. We aimed to investigate whether 300 mg thiamine daily for 12 weeks could maintain the achieved levels of fatigue in patients with IBD after a 4-week intervention with high-dose thiamine; and evaluate the effect of a 6-month period where patients were free to take oral thiamine. METHODS: A randomised, open-label, controlled trial, performed as a long-term extension (LTE) study of an initial randomised, high-dose thiamine trial. Patients were allocated 1:1 to 300 mg oral thiamine or no thiamine for 12 weeks. Subsequently, the patients were allowed to self-treat with over-the-counter (OTC) oral thiamine 6-month. RESULTS: Regardless of allocation in the LTE study fatigue severity increased in the study period. No significant effect of 300 mg oral thiamine were found, when stratifying for initial allocation in the high-dose study or fatigue level at entry in the LTE study. Patients who took OTC thiamine had lower level of fatigue 6 month later (7.8; 95% CI: 5.5-10.1) when compared to the remains (11.0; 95% CI: 9.2-12.8) (p = .02). After the 6-months follow-up without restrictions, 66% of patients had reached normal fatigue levels. CONCLUSIONS: We found no beneficial effect on fatigue from thiamine taken in doses of 300 mg per day for 12 weeks following high-dose treatment. After a 6-months follow-up without restrictions 66% had reached a normal level of fatigue. CLINICAL TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov under study identifier NCT03634735.
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Colite , Doenças Inflamatórias Intestinais , Doença Crônica , Fadiga/tratamento farmacológico , Fadiga/etiologia , Humanos , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , TiaminaRESUMO
Assessing "dysbiosis" in intestinal microbial communities is increasingly considered a routine analysis in microbiota studies, and it has added relevant information to the prediction and characterization of diseases and other adverse conditions. However, dysbiosis is not a well-defined condition. A variety of different dysbiosis indexes have been suggested and applied, but their underlying methodologies, as well as the cohorts and conditions for which they have been developed, differ considerably. To date, no comprehensive overview and comparison of all the different methodologies and applications of such indexes is available. Here, we list all types of dysbiosis indexes identified in the literature, introduce their methodology, group them into categories, and discuss their potential descriptive and clinical applications as well as their limitations. Thus, our focus is not on the implications of dysbiosis for disease but on the methodological approaches available to determine and quantify this condition.
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Testes Diagnósticos de Rotina/métodos , Disbiose/diagnóstico , Microbioma Gastrointestinal/fisiologia , Disbiose/microbiologia , HumanosRESUMO
Aim: This Danish national guideline describes the treatment of adult patients with Clostridioides (formerly Clostridium) difficile (CD) infection and the use of faecal microbiota transplantation (FMT). It suggests minimum standard for implementing an FMT service.Method: Four scientific societies appointed members for a working group which conducted a systematic literature review and agreed on the text and recommendations. All clinical recommendations were evalluated for evidence level and grade of recommendation.Results: In CD infection, the use of marketed and experimental antibiotics as well as microbiota-based therapies including FMT are described. An algorithm for evaluating treatment effect is suggested. The organisation of FMT, donor recruitment and screening, laboratory preparation, clinical application and follow-up are described.Conclusion: Updated evidence for the treatment of CD infection and the use of FMT is provided.
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Clostridioides difficile , Infecções por Clostridium , Adulto , Clostridioides , Infecções por Clostridium/terapia , Dinamarca , Transplante de Microbiota Fecal , HumanosRESUMO
BACKGROUND & AIMS: Fecal microbiota transplantation (FMT) is recommended for treatment of recurrent Clostridium difficile infection (rCDI). We performed a single-center randomized trial to compare the effects of FMT with those of fidaxomicin and vancomycin. METHODS: We studied consecutive adults with rCDI seen at a gastroenterology clinic in Denmark from April 5, 2016 through June 10, 2018. Patients were randomly assigned to a group that received FMT, applied by colonoscopy or nasojejunal tube, after 4-10 days of vancomycin (125 mg 4 times daily; FMTv; n = 24), 10 days of fidaxomicin (200 mg twice daily; n = 24), or 10 days of vancomycin (125 mg 4 times daily; n = 16). Patients who had rCDI after this course of treatment and patients who could not be randomly assigned to groups were offered rescue FMTv. The primary outcome was combined clinical resolution and a negative result from a polymerase chain reaction test for Clostridium difficile (CD) toxin 8 weeks after the allocated treatment. Secondary end points included clinical resolution at week 8. RESULTS: All 64 patients received their assigned treatment. The combination of clinical resolution and negative results from the test for CD were observed in 17 patients given FMTv (71%), 8 patients given fidaxomicin (33%), and 3 patients given vancomycin (19%; P = .009 for FMTv vs fidaxomicin; P = .001 for FMTv vs vancomycin; P = .31 for fidaxomicin vs vancomycin). Clinical resolution was observed in 22 patients given FMTv (92%), 10 patients given fidaxomicin (42%), and 3 patients given vancomycin (19%; P = .0002; P < .0001; P = .13). Results did not differ significantly between patients who received FMTv as their initial therapy and patients who received rescue FMTv. There was 1 serious adverse event that might have been related to FMTv. CONCLUSIONS: In a randomized trial of patients with rCDI, we found the FMTv combination superior to fidaxomicin or vancomycin based on end points of clinical and microbiological resolution or clinical resolution alone. ClinicalTrials.gov, number NCT02743234; EudraCT, j.no 2015-003004-24.
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Antibacterianos/uso terapêutico , Clostridioides difficile/efeitos dos fármacos , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal , Fidaxomicina/uso terapêutico , Vancomicina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Clostridioides difficile/patogenicidade , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/microbiologia , Dinamarca , Transplante de Microbiota Fecal/efeitos adversos , Feminino , Fidaxomicina/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Vancomicina/efeitos adversos , Adulto JovemRESUMO
Clostridioides difficile infection may be complicated by co-infection with other pathogens. We here describe the successful use of faecal microbiota transplantation to eradicate concomitant C. difficile and extensively drug-resistant (XDR) KPC-producing Klebsiella pneumoniae. Donor microbiota efficiently engrafted in the patient, and a donor-like microbial assemblage persisted in the patient during six months follow-up. The report explores the potential for the donor microbiota to eradicate and replace multi-resistant microorganisms.
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Infecções por Clostridium/terapia , Coinfecção/terapia , Transplante de Microbiota Fecal , Infecções por Klebsiella/terapia , Idoso , Antibacterianos/uso terapêutico , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/microbiologia , Coinfecção/microbiologia , Farmacorresistência Bacteriana Múltipla , Feminino , Microbioma Gastrointestinal , Humanos , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/isolamento & purificaçãoRESUMO
BACKGROUND: Clostridioides (Clostridium) difficile infection (CDI) is a leading cause of antibiotics-associated diarrhoea. Faecal microbiota transplantation (FMT) is effective for recurrent CDI and may be provided as a home treatment to frail, older people. METHODS: We present four consecutive patients with recurrent CDI, treated at home using nasojejunal tube-delivered or encapsulated donor faeces. The primary outcome was combined clinical resolution and a negative CD toxin test 8 weeks post-treatment. RESULTS: All four patients had severe CDI and all improved clinically following one FMT. Sustained resolution following one FMT was observed in one patient. Two patients had recurrence and received a second FMT using capsules; both achieved resolution. One patient who had recurrence declined from further FMT due to fear of relapse and was established on long-term vancomycin. No adverse events related to FMT were observed. CONCLUSION: Frail older people may benefit from FMT. Home treatment is a viable option and may be considered both for clinical cure and for palliation.
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Clostridioides difficile , Infecções por Clostridium , Idoso , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/terapia , Transplante de Microbiota Fecal/efeitos adversos , Idoso Fragilizado , Humanos , Recidiva , Resultado do TratamentoRESUMO
Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection and is potentially beneficial in other microbiota-related disorders. The provision of FMT in routine clinical practice requires an extensive infrastructure that is reliant on voluntary donors. Alongside an increasing demand for FMT, the logistic barriers of a large-scale donor-dependent operation and the difficulties among health authorities to regulate FMT limit the dissemination of sustainable FMT services. Blood centers are large organizations that handle a multitude of donor-dependent operations on a daily basis. Blood and feces share many of the same dependencies, and feces may present a new opportunity for the blood services to handle. In this paper, we describe how an FMT service may be established and embedded within the blood service infrastructure, and we explain the benefits of using blood donors as feces donors. We further explore the current indications of FMT, the challenges related to the lack of legislation, and the future perspectives for blood banks to meet a new and increasing demand.
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Bancos de Sangue/organização & administração , Bancos de Sangue/tendências , Transplante de Microbiota Fecal , Fezes , Bancos de Sangue/legislação & jurisprudência , Doadores de Sangue , Seleção do Doador/métodos , Seleção do Doador/normas , Seleção do Doador/tendências , Transplante de Microbiota Fecal/métodos , Transplante de Microbiota Fecal/normas , Transplante de Microbiota Fecal/estatística & dados numéricos , Transplante de Microbiota Fecal/tendências , Necessidades e Demandas de Serviços de Saúde , Humanos , Legislação Médica/normas , Guias de Prática Clínica como Assunto/normas , Setor Público , Medição de Risco , Armazenamento de Sangue/métodosRESUMO
OBJECTIVE: Anti-TNF-α treatment constitutes a mainstay in the treatment of Crohn's disease (CD), but its mechanisms of action are not fully understood. We aimed to investigate the effects of adalimumab, a human monoclonal TNF-α antibody, on macrophage (MQ) and dendritic cell (DC) subsets in mucosal biopsies and peripheral blood. MATERIAL AND METHODS: Intestinal biopsies and blood samples were obtained from 12 different CD patients both before and 4 weeks after the initiation of the induction of adalimumab treatment. Endoscopic disease activity was estimated by the Simple Endoscopic Score for Crohn's Disease. Biopsies were obtained from inflamed and non-inflamed areas. The numbers of lamina propria CD14 (+) DR(int) and CD14 (+) DR(hi) MQs, CD141(+), CD141(-) and CD103(+) DCs subsets, and circulating monocytes and DCs were analyzed using flow cytometry. RESULTS: At baseline, we observed higher numbers of DR(int) MQs and lower numbers of CD103(+) DCs in inflamed versus non-inflamed mucosa [843 vs. 391/10(5) lamina propria mononuclear cells (LPMCs) (p < 0.05) and 9 vs. 19 × 10(5) LPMCs (p = 0.01), respectively]. After four weeks of adalimumab treatment, the numbers of DR(int) MQs decreased [843 to 379/10(5) LPMCs (p = 0.03)], whereas the numbers of CD103(+) DCs increased [9-20 × 10(5) LPMCs (p = 0.003)] compared with baseline. In peripheral blood, no alterations were observed in monocyte or DC numbers between baseline and week 4. CONCLUSIONS: In CD, mucosal inflammation is associated with high numbers of DR(int) MQs and low numbers of CD103(+) DCs. This composition of intestinal myeloid subsets is reversed by anti-TNF-α treatment. These results suggest that DR(int) MQs play a pivotal role in CD inflammation.
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Adalimumab/farmacologia , Anti-Inflamatórios/farmacologia , Doença de Crohn/tratamento farmacológico , Células Dendríticas/efeitos dos fármacos , Mucosa Intestinal/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Adalimumab/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antígenos CD/metabolismo , Biomarcadores/metabolismo , Biópsia , Colo/efeitos dos fármacos , Colo/imunologia , Colo/patologia , Doença de Crohn/imunologia , Doença de Crohn/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Feminino , Citometria de Fluxo , Humanos , Íleo/efeitos dos fármacos , Íleo/imunologia , Íleo/patologia , Cadeias alfa de Integrinas/metabolismo , Mucosa Intestinal/patologia , Macrófagos/imunologia , Macrófagos/patologia , MasculinoAssuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Espermatozoides/efeitos dos fármacos , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Estudos de Casos e Controles , DNA/genética , Fragmentação do DNA , Humanos , Masculino , Pessoa de Meia-Idade , Segurança do Paciente , Valores de Referência , Espermatozoides/anormalidades , Adulto JovemRESUMO
OBJECTIVES: Adherence to medical treatment among women with Crohn's disease (CD) in the postpartum period has never been examined. The impact of breast-feeding on disease activity remains controversial. We aimed to assess rates of non-adherence to medical treatment among women with CD in the postpartum period. Further, to assess breast-feeding rates and the impact of breast-feeding on the risk of relapse. METHODS: Within a population of 1.6 million, we identified 154 women with CD who had given birth within a 6-year period. We combined questionnaire data, data from medical records and public register data. We used logistic regression to estimate prevalence odds ratios (POR) for non-adherence, relapse and breast-feeding according to different predictors. RESULTS: Among 105 (80%) respondents, 59 (56%) reported taking medication. Of these, 66.1% reported to be adherent to medical treatment. Fear of medication transmission to the breast milk was stated as the reason for non-adherence in 60%. Those who received counselling regarding medical treatment were less likely to be non-adherent (POR 0.55, 95% confidence interval [CI] 0.1-2.5). In total, 87.6% were breast-feeding. Breast-feeding rates did not vary by medical treatment. Predictors for relapse in CD were smoking (POR 1.85, 95% CI 0.62-5.54) and non-adherence among medical treated (POR 1.25, 95% CI 0.26-6.00). Breast-feeding seemed protective against relapse (POR 0.33, 95% CI 0.10-1.26). CONCLUSIONS: Adherence to medical treatment in the postpartum period was high, and counselling seemed to increase adherence. Relapse may be explained by non-adherence or smoking while breast-feeding seemed protective.
Assuntos
Aleitamento Materno/estatística & dados numéricos , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , Adesão à Medicação/estatística & dados numéricos , Período Pós-Parto , Complicações na Gravidez , Autorrelato , Adulto , Doença de Crohn/diagnóstico , Dinamarca/epidemiologia , Progressão da Doença , Feminino , Humanos , Incidência , Gravidez , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Fumar/efeitos adversos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE. Little is known about predictors for adverse pregnancy outcomes among women with Crohn's disease (CD). In this population-based study, we examined pregnancy outcomes in CD stratified by medical treatment and smoking status while accounting for disease activity. METHODS. In two Danish regions with a population of 1.6 million, we identified 154 CD women who had given birth within a 6-year period. We combined questionnaire data, prescription data, data from medical records and population-based medical databases. We used logistic regression to estimate prevalence odds ratios (POR) for adverse pregnancy outcomes by different predictors. RESULTS. Among 105 (80%) respondents, 55 (52%) reported taking medication during pregnancy. The majority (95%) were in disease remission. The children's mean birth weight did not differ by maternal medical treatment. As expected, smoking was a predictor of low birth weight. Mean birth weight in children of smokers in medical treatment was significantly reduced by 274 g compared with children of non-smokers who received medical treatment. In children of women without medical treatment, this difference was 126 g between smokers and non-smokers. Women in medical treatment did not have an increased risk of preterm delivery (POR 0.71; 95% confidence interval (CI) 0.18-2.79), congenital malformations (POR 0.60; 0.10-3.76) or cesarean section (POR 1.40; 0.63-3.08). CONCLUSIon. In CD, smoking was negatively associated with child birth weight. This association was most pronounced among women who received medical treatment. Maternal medical treatment for CD did not seem to be a risk factor for adverse pregnancy outcomes.
Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Peso ao Nascer , Doença de Crohn/tratamento farmacológico , Imunossupressores/efeitos adversos , Complicações na Gravidez/tratamento farmacológico , Resultado da Gravidez , Fumar/efeitos adversos , Adulto , Anti-Inflamatórios não Esteroides/uso terapêutico , Peso ao Nascer/efeitos dos fármacos , Anormalidades Congênitas/etiologia , Doença de Crohn/fisiopatologia , Feminino , Humanos , Imunossupressores/uso terapêutico , Quimioterapia de Indução , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , Modelos Logísticos , Razão de Chances , Gravidez , Complicações na Gravidez/fisiopatologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , NatimortoRESUMO
BACKGROUND: Patients with an ileostomy often have impaired quality of life, sodium depletion, secondary hyperaldosteronism, and other organ-specific pathologies. The osmolality of oral supplements influences ileostomy output and increases sodium loss. We hypothesized the existence of an osmolality range in which fluid absorption and secondary natriuresis are optimal. METHODS: This was a single-center, quasi-randomized crossover intervention study, including patients with an ileostomy and no home parenteral support. After an 8-h fasting period, each patient ingested 500 mL of 3-18 different oral supplements and a standardized meal during the various intervention periods, followed by a 6-h collection of ileostomy and urine outputs. The primary outcome was 6-h ileostomy output. RESULTS: A total of 14 ileostomy patients with a median age of 65 years (interquartile range 38-70 years) were included. The association between osmolalities (range 5-1352 mOsm/kg) and ileostomy output forecasted an S-curve. A linear association between osmolality of oral supplements (range 290-600 mOsm/kg) and ileostomy output was identified and assessed with a mixed-effects model. Ileostomy output increased by 57 g/6 h (95% confidence interval (CI) 21-94) when the oral supplement osmolality increased by 100 mOsm/kg (p = 0.005). CONCLUSION: Osmolality in oral supplements correlated with ileostomy output. Our results indicate that patients with an ileostomy may benefit from increased ingestion of oral supplements with osmolalities between 100 and 290 mOsm/kg. We define this range as the Goldilocks zone, equivalent to optimal fluid and electrolyte absorption.