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Pancreas-derived islet amyloid polypeptide (IAPP) aggregates and deposits in the pancreas and periphery of Type 2 Diabetes (T2D) patients, contributing to diabetic complications. The excess IAPP can be removed by autoantibodies, and increased levels of immunoglobulin (Ig) G against IAPP have been reported in T2D patients. However, whether other Ig classes are also affected and if the levels can be managed is less known. This pre-post study examines IgA levels against IAPP oligomers (IAPPO-IgA) in T2D patients and assesses the impact of the Okinawa-based Nordic (O-BN) diet-a low-carbohydrate, high-fiber diet-on these levels after following the diet for 3 months. IAPP, IAPPO-IgA, and total IgA levels were measured in plasma and fecal samples from n = 30 T2D patients collected at baseline, after 3 months of diet, and after additional 4 months of unrestricted diets (a clinical follow-up). The IAPP and IAPPO-IgA levels were significantly lower after 3 months, with the latter also being significantly reduced at the clinical follow-up. The reduction in plasma IAPP and IAPPO-IgA levels correlated with reductions in plasma levels of metabolic and inflammatory markers. Hence, following the O-BN diet for at least 3 months is sufficient to reduce circulating IAPP and IAPPO-IgA levels, which may be principal in managing T2D.
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Diabetes Mellitus Tipo 2 , Imunoglobulina A , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Humanos , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Imunoglobulina A/sangue , Imunoglobulina A/metabolismo , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Japão , AdultoRESUMO
Despite diagnostic algorithms, identification of venous thromboembolism (VTE) in emergency departments (ED) remains a challenge. We evaluated symptoms, background, and laboratory data in 27,647 ED patients presenting with pain, swelling, or other symptoms from the extremities, and identified predictors of VTE diagnosis within one year. Predictors of a clinical decision to perform phlebography, ultrasound, or computer tomography (CT) angiography of pelvic, lower, or upper extremity veins, CT of pulmonary arteries, or pulmonary scintigraphy at the ED or within 30 days, and the results of such investigations were also evaluated. A total of 3195 patients (11.6%) were diagnosed with VTE within one year. In adjusted analysis of patients in whom all laboratory data were available, a d-dimer value ≥ 0.5 mg/l (odds ratio [OR]: 2.602; 95% confidence interval [CI] 1.894-3.575; p < 0.001) at the ED and a previous diagnosis of VTE (OR: 6.037; CI 4.465-8.162; p < 0.001) independently predicted VTE within one year. Of diagnosed patients, 2355 (73.7%) had undergone imaging within 30 days after the ED visit and 1730 (54.1%) were diagnosed at this examination. Lower age (OR: 0.984; CI 0.972-0.997; p = 0.014), higher blood hemoglobin (OR: 1.023; CI 1.010-1.037; p < 0.001), C-reactive protein (OR: 2.229; CI 1.433-3.468; p < 0.001), d-dimer (OR: 8.729; CI 5.614-13.574; p < 0.001), and previous VTE (OR: 7.796; CI 5.193-11.705; p < 0.001) predicted VTE on imaging within 30 days, whereas female sex (OR 0.602 [95% CI 0.392-0.924]; p = 0.020) and a previous diagnosis of ischemic heart disease (OR 0.254 [95% CI 0.113-0.571]; p = 0.001) were negative predictors of VTE. In conclusion, analysis of 27,647 ED patients with extremity symptoms confirmed the importance of well-established risk factors for VTE. Many patients developing VTE within one year had initial negative imaging, highlighting the importance of continued symptom vigilance.
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Background: Irritable bowel syndrome (IBS) is common with a global prevalence of 4%. Dietary regimes with a low content of fermentable oligo-, di-, and monosaccharides and polyol (FODMAP) or a starch- and sucrose-reduced diet (SSRD) have proven to be efficient. The aim of the present study was to describe the recruitment process for a randomized dietary trial with low FODMAP or SSRD for 4 weeks with a follow-up period of 5 months. The results of the dietary trial itself are not included in this paper but will be presented in another publication. Methods: The County of Skåne, with 1,41 million inhabitants, was used as a base to perform a dietary trial in which IBS patients, age 18-70 years, were randomized to either low FODMAP or SSRD for 4 weeks. The estimated number of IBS patients in the actual age span was approximately 32,000. The trial was announced through lectures, letters to all primary healthcare centers (n=203), social media (two campaigns), and invitations to IBS patients identified in medical records (n=744). Results: Three referrals arrived from the healthcare system, 17 patients contacted the investigators in person after receiving information from their healthcare center, and four patients contacted the investigators after recommendations from friends. Of these, 14 were enrolled in the study. From social media, 218 names were delivered, of which 93 fulfilled the study criteria and were willing to participate when contacted by the investigators (42.7%). Of the 3587 identified IBS patients in medical records in close proximity to the hospital, 744 were randomly contacted. Forty-eight patients (6.5 %) were willing to be included in the study. Thus, 155 patients with IBS were included in this study. Conclusions: The inclusion rate for dietary intervention was very low considering the large population informed about the study. Announcements on social media seem to be the best way to recruit patients for intervention. Trial registration: NCT05192603, 29/11/2021, ClinicalTrials.gov. The PRS URL is https://register.clinicaltrials.gov.
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Síndrome do Intestino Irritável , Seleção de Pacientes , Humanos , Síndrome do Intestino Irritável/dietoterapia , Adulto , Pessoa de Meia-Idade , Masculino , Feminino , Adolescente , Idoso , Adulto JovemRESUMO
Microscopic colitis (MC) is classified as collagenous colitis (CC) and lymphocytic colitis (LC). Genetic associations between CC and human leucocyte antigens (HLAs) have been found, with smoking being a predisposing external factor. Smoking has a great impact on metabolomics. The aim of this explorative study was to analyze global metabolomics in MC and to examine whether the metabolomic profile differed regarding the type and course of MC, the presence of IBS-like symptoms, treatment, and smoking habits. Of the 240 identified women with MC aged ≤73 years, 131 completed the study questionnaire; the Rome III questionnaire; and the Visual Analog Scale for Irritable Bowel Syndrome (VAS-IBS). Blood samples were analyzed by ultra-high-performance liquid chromatograph mass spectrometry (UHLC-MS/UHPLC-MSMS). The women, 63.1 (58.7-67.2) years old, were categorized based on CC (n = 76) and LC (n = 55); one episode or refractory MC; IBS-like symptoms or not; use of corticosteroids or not; and smoking habits. The only metabolomic differences found in the univariate model after adjustment for false discovery rate (FDR) were between smokers and non-smokers. Serotonin was markedly increased in smokers (p < 0.001). No clear patterns appeared when conducting a principal component analysis (PCA). No differences in the metabolomic profile were found depending on the type or clinical course of the disease, neither in the whole MC group nor in the subgroup analysis of CC.
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BACKGROUND: In the European Union alone, more than 100 million people present to the emergency department (ED) each year, and this has increased steadily year-on-year by 2-3%. Better patient management decisions have the potential to reduce ED crowding, the number of diagnostic tests, the use of inpatient beds, and healthcare costs. METHODS: We have established the Skåne Emergency Medicine (SEM) cohort for developing clinical decision support systems (CDSS) based on artificial intelligence or machine learning as well as traditional statistical methods. The SEM cohort consists of 325 539 unselected unique patients with 630 275 visits from January 1st, 2017 to December 31st, 2018 at eight EDs in the region Skåne in southern Sweden. Data on sociodemographics, previous diseases and current medication are available for each ED patient visit, as well as their chief complaint, test results, disposition and the outcome in the form of subsequent diagnoses, treatments, healthcare costs and mortality within a follow-up period of at least 30 days, and up to 3 years. DISCUSSION: The SEM cohort provides a platform for CDSS research, and we welcome collaboration. In addition, SEM's large amount of real-world patient data with almost complete short-term follow-up will allow research in epidemiology, patient management, diagnostics, prognostics, ED crowding, resource allocation, and social medicine.
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Serviço Hospitalar de Emergência , Humanos , Suécia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Medicina de Emergência , Feminino , Masculino , Sistemas de Apoio a Decisões Clínicas , Estudos de Coortes , Inteligência Artificial , AdultoRESUMO
The pathogenesis of appendicitis is not understood fully, and the diagnosis can be challenging. Previous research has suggested an association between a T helper (Th) 1-dependent immune response and complicated appendicitis. This prospective cohort study aimed to evaluate the association between serum concentrations of the Th1-associated cytokines interleukin (IL)-1α, IL-1ß, IL-2, IL-6, IL-10, IL-17A and tumor necrosis factor beta (TNF-ß) and the risk of complicated appendicitis in children. Appendicitis severity was determined through histopathological examination. A total of 137 children < 15 years with appendicitis were included with a median age of 10 years (IQR 8-12); 86 (63%) were boys, and 58 (42%) had complicated appendicitis. Children with complicated appendicitis had significantly higher concentrations of serum IL-6 and IL-10, and lower of TNF-ß. After adjustment for age, symptom duration, and presence of appendicolith in a multivariable logistic regression, a higher concentration of IL-6 remained associated with an increased risk of complicated appendicitis (aOR 1.001 [95% CI 1.000-1.002], p = 0.02). Serum concentrations of IL-1α, IL-1ß, IL-2, IL-10, IL-17A and TNF-ß were not significantly associated with the risk of complicated appendicitis. In conclusion, our results suggests that the systemic inflammatory response in complicated appendicitis is complex and not solely Th1-dependent.
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Apendicite , Citocinas , Masculino , Humanos , Criança , Feminino , Interleucina-10 , Interleucina-17 , Apendicite/complicações , Interleucina-6 , Interleucina-2 , Linfotoxina-alfa , Estudos Prospectivos , Interleucina-1betaRESUMO
BACKGROUND: Microscopic colitis (MC) is considered a chronic disease associated with autoimmune disease, smoking, and drugs. The aim was to examine the association between MC and celiac disease, adjusted for smoking, considering subtypes and clinical course of the disease in a retrospectively collected female cohort. METHODS: Women (n = 240), ≤ 73 years, diagnosed as MC in medical records or pathological registers were invited. One hundred and fifty-eight women accepted to be included. Participants completed a study questionnaire about sociodemographic factors, lifestyle habits, and medical history; the Rome III questionnaire; and the visual analog scale for irritable bowel syndrome (VAS-IBS). Participants were categorized into collagenous colitis (CC) (n = 92) and lymphocytic colitis (LC) (n = 66) or MC with one episode of the disease (n = 70) and refractory MC (n = 88). Presence of IBS-like symptoms were noted. Blood samples were collected and analyzed for anti-transglutaminase antibodies. Differences between groups were calculated and logistic regression was adjusted for smoking habits. RESULTS: MC and celiac disease debuted simultaneously in half of the cases. Celiac disease was most prevalent in LC (12.1% vs. 3.3%; p = 0.05) and MC with one episode (12.9% vs. 2.3%; p = 0.01). Anti-transglutaminase antibodies were found in one patient with one episode of MC. Corticosteroid use was most often found in CC (37.0% vs. 21.2%; p = 0.037) and refractory MC (38.6% vs. 20.0%; p = 0.015). Past smokers were most prevalent in patients with one episode of MC (54.3 vs. 29.5%; p = 0.007). Current smoking was the smoking habit with highest prevalence of IBS-like symptoms. When adjusted for smoking habits, celiac disease was associated with LC (OR: 4.222; 95% CI: 1.020-17.469; p = 0.047) and tended to be inversely associated with refractory MC (OR: 0.210; 95% CI: 0.042-1.506; p = 0.058). CONCLUSION: Celiac disease is most common in patients with one episode of LC. The question remains whether LC in combination with celiac disease should be classified as celiac disease or two different entities.
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Doença Celíaca , Colite Colagenosa , Colite Linfocítica , Colite Microscópica , Síndrome do Intestino Irritável , Humanos , Feminino , Colite Linfocítica/epidemiologia , Colite Linfocítica/complicações , Colite Linfocítica/patologia , Síndrome do Intestino Irritável/epidemiologia , Síndrome do Intestino Irritável/complicações , Estudos Retrospectivos , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Colite Microscópica/epidemiologia , Colite Microscópica/patologia , Colite Colagenosa/epidemiologia , Colite Colagenosa/complicações , Colite Colagenosa/patologiaRESUMO
Gastrointestinal (GI) symptoms are common in postural orthostatic tachycardia syndrome (POTS). We aimed to explore the prevalence and severity of GI symptoms in POTS, and to investigate immunological factors, hemodynamic findings, and their possible association with GI symptoms in POTS. Forty-three patients (93% female, median age 30.6 (26.0-41.0) years), previously diagnosed with POTS and 74 healthy controls (78% female, median age 35.6 (28.8-41.7) years) were included. The participants completed a questionnaire including prevalence of GI symptoms, the irritable bowel syndrome severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). All POTS patients were previously examined by tilt test (2010-2021) and the vast majority with more recent active standing test (2017-2021), which included monitoring of heart rate (HR). ΔHR was calculated as difference between supine and upright position. Continuous variables from IBS-SSS and VAS-IBS were correlated to ΔHR. A microarray containing several autoantigens commonly targeted in systemic autoimmune disorders was used to assess prevalent autoantibodies in POTS and controls. Total IgE and S-tryptase were analyzed. GI symptoms were more prevalent and severe in POTS than in controls; nausea being the most prevalent (79.1% vs 4.9%, p < 0.001) and bloating and flatulence being the most severe (median 65 (25-88) vs 0 (0-14), p < 0.001). The median total IBS-SSS was 213 (135-319) in POTS vs 13 (0-54) in controls (p < 0.001). Total IBS-SSS was associated with low psychological wellbeing (r = 0.539, p < 0.001) in POTS. ΔHRmax correlated inversely with abdominal pain (r = -0.406, p = 0.007). After adjustments for psychological wellbeing, total IBS-SSS still associated inversely with ΔHR10min (ß: 4.748; 95% CI: -9.172 to -0.324; p = 0.036). Similar results were seen with active standing test. The prevalence of autoantibodies did not differ between POTS and controls (29.4% vs 33.3%, p = 0.803). There was no association between GI symptoms and autoantibody status. Total IgE and tryptase were elevated in a few cases. This study confirms the high prevalence of GI symptoms in POTS. More pronounced tachycardia upon tilt table testing seems to be inversely correlated with severity of chronic GI symptoms in POTS. This study did not support the hypothesis that POTS is associated with immunological factors.
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Postural Orthostatic Tachycardia Syndrome (POTS) reflects an autonomic dysfunction, which can occur as a complication to COVID-19. Our aim was to examine gastrointestinal symptoms and gut microbiota composition in patients with POTS and post-acute COVID-19 syndrome (PACS), compared with controls. POTS patients (n = 27), PACS patients (n = 32) and controls (n = 39) delivered fecal samples and completed a 4-day food diary, irritable bowel syndrome-severity scoring system (IBS-SSS), and visual analog scale for IBS (VAS-IBS). A total of 98 DNA aliquots were sequenced to an average depth of 28.3 million (M) read pairs (Illumina 2 × 150 PE) per sample. Diversity and taxonomic levels of the microbiome, as well as functional abundances were calculated for POTS and PACS groups, then compared with controls. There were several differences in taxonomic composition between POTS and controls, whereas only the abundance of Ascomycota and Firmicutes differed between PACS and controls. The clinical variables total IBS-SSS, fatigue, and bloating and flatulence significantly correlated with multiple individual taxa abundances, alpha diversity, and functional abundances. We conclude that POTS, and to a less extent PACS, are associated with differences in gut microbiota composition in diversity and at several taxonomic levels. Clinical symptoms are correlated with both alpha diversity and taxonomic and functional abundances.
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COVID-19 , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Síndrome da Taquicardia Postural Ortostática , Humanos , Síndrome da Taquicardia Postural Ortostática/diagnóstico , Síndrome do Intestino Irritável/complicações , Síndrome de COVID-19 Pós-Aguda , COVID-19/complicaçõesRESUMO
BACKGROUND: Medical student master's theses are often carried out as research projects, and some are published as research papers in journals. We investigated the percentage of master's theses conducted by 5th -year students at the Medical Degree Program at Lund University, Sweden, that subsequently served as the basis for research publications. In addition, we explored both student and supervisor experiences with the publishing process. METHODS: A cohort of four semesters of student data covering the period from 2019 to 2020 (n = 446) was searched in PubMed, Embase and the Web of Science to assess whether they had been published as research papers. Surveys were sent to students (n = 121) and supervisors (n = 77) to explore their experiences with the publishing process. RESULTS: We found that 33% (149 of 446) of the students in the 2019-2020 cohort subsequently published their theses, and 50% of these students were listed as first authors. Most students published original research. Students (n = 21) and supervisors (n = 44) reported that the publishing process was time-consuming and that students needed multilevel support from supervisors to achieve successful publication. The publishing process was reported by 79% of the students to have led to additional learning. Most of the papers (126 of 149, 85%) had a clinical or patient-oriented focus. CONCLUSION: A high percentage of the student publications in which students are listed as first authors require engagement from both students and supervisors. Supervisors play an essential role in supporting students in a successful publication process. Most of the published papers were either clinical or patient-oriented research.
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Estudantes de Medicina , Humanos , Editoração , Faculdades de Medicina , Aprendizagem , PesquisadoresRESUMO
BACKGROUND AND AIMS: Microscopic colitis [MC] is currently regarded as an inflammatory bowel disease that manifests as two subtypes: collagenous colitis [CC] and lymphocytic colitis [LC]. Whether these represent a clinical continuum or distinct entities is, however, an open question. Genetic investigations may contribute important insight into their respective pathophysiologies. METHODS: We conducted a genome-wide association study [GWAS] meta-analysis in 1498 CC, 373 LC patients, and 13 487 controls from Europe and the USA, combined with publicly available MC GWAS data from UK Biobank and FinnGen [2599 MC cases and 552 343 controls in total]. Human leukocyte antigen [HLA] alleles and polymorphic residues were imputed and tested for association, including conditional analyses for the identification of key causative variants and residues. Genetic correlations with other traits and diagnoses were also studied. RESULTS: We detected strong HLA association with CC, and conditional analyses highlighted the DRB1*03:01 allele and its residues Y26, N77, and R74 as key to this association (best pâ =â 1.4â ×â 10-23, odds ratio [OR]â =â 1.96). Nominally significant genetic correlations were detected between CC and pneumonia [rgâ =â 0.77; pâ =â 0.048] and oesophageal diseases [rgâ =â 0.45, pâ =â 0.023]. An additional locus was identified in MC GWAS analyses near the CLEC16A and RMI2 genes on chromosome 16 [rs35099084, pâ =â 2.0â ×â 10-8, ORâ =â 1.31]. No significant association was detected for LC. CONCLUSION: Our results suggest CC and LC have distinct pathophysiological underpinnings, characterised by an HLA predisposing role only in CC. This challenges existing classifications, eventually calling for a re-evaluation of the utility of MC umbrella definitions.
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Colite Colagenosa , Colite Linfocítica , Colite Microscópica , Humanos , Estudo de Associação Genômica Ampla , Antígenos HLA/genética , Antígenos de Histocompatibilidade Classe II , Colite Microscópica/genética , Colite Linfocítica/genéticaRESUMO
OBJECTIVES: A starch- and sucrose-reduced diet has been found to improve gastrointestinal and extraintestinal symptoms in irritable bowel syndrome, as well as reduce weight and improve psychological well-being. Our hypothesis was that a starch- and sucrose-reduced diet would also be beneficial in other conditions with similar symptoms. The aim of the present research letter was to describe the role of a starch- and sucrose-reduced diet in a pilot project in patients with diarrhea having varying causes. METHODS: One man, age 36 y, suffering from functional diarrhea and one woman, 56 y, suffering from microscopic colitis, were randomized to a starch- and sucrose-reduced diet for 4 wk. At baseline, dietary information was given, and blood samples collected. Weight and waist circumference were measured. The participants completed the irritable bowel syndrome severity scoring system for evaluating specific gastrointestinal and extraintestinal symptoms and visual analog scale for irritable bowel syndrome for evaluation of specific gastrointestinal symptoms and psychological well-being. The degrees of satiety and sweet craving were measured on visual analog scales. After 4 wk, all procedures were repeated. RESULTS: Weight, body mass index, and waist circumference were decreased during the intervention. The total amount of gastrointestinal symptoms was decreased in the participants with functional diarrhea, and diarrhea and bloating were decreased in both participants. Both had reduced extraintestinal symptoms and improved psychological well-being. Blood levels had mainly unchanged or slightly increased values of measurements reflecting nutrient intake. CONCLUSIONS: A starch- and sucrose-reduced diet may lead to weight reduction, reduced symptoms, and improved well-being in several patient categories, not only in patients suffering from irritable bowel syndrome. Future randomized trials should be done.
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Gastroenteropatias , Síndrome do Intestino Irritável , Masculino , Feminino , Humanos , Adulto , Sacarose , Amido , Projetos Piloto , Diarreia/complicações , Dieta , Gastroenteropatias/etiologiaRESUMO
BACKGROUND: Endometriosis and irritable bowel syndrome (IBS) have similar symptoms, pathogenesis, and risk factors. These diagnoses often coexist and are frequently misdiagnosed leading to diagnostic delays. This study of a population-based cohort aimed to investigate associations relating to endometriosis and IBS and to compare gastrointestinal symptoms between endometriosis and IBS. METHOD: The study cohort included women from the Malmö Offspring Study with information about endometriosis and IBS diagnoses from the National Board of Health and Welfare. The participants answered a questionnaire about lifestyle habits, medical and drug history, and self-reported IBS. The visual analog scale for IBS was used to estimate gastrointestinal symptoms the past 2 weeks. Endometriosis diagnosis and self-reported IBS were used as dependent variables to study associations with age, body mass index (BMI), education, occupation, marital status, smoking, alcohol habits, and physical activity using logistic regression. Mann-Whitney U Test or Kruskal-Wallis tests were used to calculate the differences in symptoms between groups. RESULTS: Of the 2,200 women with information from medical records, 72 participants had endometriosis; 21 (29.2%) of these had self-reported IBS. Of the 1,915 participants who had answered the questionnaire, 436 (22.8%) had self-reported IBS. Endometriosis was associated with IBS (OR:1.86; 95%CI:1.06-3.26; p = 0.029), as well as with age 50-59 years (OR:6.92; 95%CI:1.97-24.32; p = 0.003), age ≥ 60 years (OR:6.27; 95%CI:1.56-25.17; p = 0.010), sick leave (OR:2.43; 95%CI:1.08-5.48; p = 0.033), and former smoking (OR:3.02; 95%CI:1.19-7.68; p = 0.020). There was an inverse association with BMI (OR:0.36; 95%CI:0.14-4.91; p = 0.031). IBS was associated with endometriosis (OR:1.77; 95%CI:1.02-3.07; p = 0.041) and sick leave (OR:1.77; 95%CI:1.14-2.73; p = 0.010), with a tendency to association with smoking (OR:1.30; 95%CI:0.98-1.72; p = 0.071). When excluding participants using drugs associated with IBS, the condition was associated with current smoking (OR:1.39; 95%CI:1.03-1.89; p = 0.033) and inversely with age 50-59 years (OR:0.58; 95%CI:0.38-0.90; p = 0.015). There were differences in the gastrointestinal symptoms between IBS and healthy participants, but not between endometriosis and IBS or healthy participants. CONCLUSION: There were associations between endometriosis and IBS, without differences in gastrointestinal symptoms. Both IBS and endometriosis were associated with smoking and sick leave. Whether the associations reflect causality or depend on common risk factors and pathogenesis remains to be determined.
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Endometriose , Gastroenteropatias , Síndrome do Intestino Irritável , Humanos , Feminino , Pessoa de Meia-Idade , Síndrome do Intestino Irritável/complicações , Síndrome do Intestino Irritável/epidemiologia , Endometriose/complicações , Endometriose/epidemiologia , Gastroenteropatias/complicações , Fatores de Risco , Fumar/epidemiologia , Inquéritos e QuestionáriosRESUMO
Dietary interventions modify gut microbiota and clinical outcomes. Weight reduction and improved glucose and lipid homeostasis were observed after adopting an Okinawan-based Nordic diet (O-BN) in individuals with type 2 diabetes. The aim of the present study was to explore changes in metabolomics and gut microbiota during O-BN and correlate changes with clinical outcomes. A total of 30 patients (17 women), aged 57.5 ± 8.2 years, diabetes duration 10.4 ± 7.6 years, 90% over-weight, were included. Participants were provided an O-BN for 12 weeks. Before and after intervention, and 16 weeks afterwards, anthropometry and clinical data were estimated and questionnaires were collected, as well as samples of blood and stool. Plasma metabolomics were determined by gas- (GC-MS) or liquid- (LC-MS) chromatography-based mass spectrometry and fecal microbiota determination was based on 16S rRNA amplicons from regions V1-V2. During the intervention, weight (6.8%), waist circumference (6.1%), and levels of glucose, HbA1c, insulin, triglycerides, and cholesterol were decreased. Of 602 metabolites, 323 were changed for any or both periods; 199 (101 lipids) metabolites were decreased while 58 (43 lipids) metabolites were increased during the intervention. Changes in glucose homeostasis were linked to changes in, e.g., 1,5-anhydroglucitol, thyroxine, and chiro-inositol. Changes of microbe beta diversity correlated positively with food components and negatively with IL-18 (p = 0.045). Abundance differences at phylum and genus levels were found. Abundances of Actinobacteria, Bacteroidetes, Firmicutes, and Verrucomicrobia correlated with anthropometry, HbA1c, lipids, inflammation, and food. Changes in metabolites and microbiota were reversed after the intervention. The O-BN-induced changes in metabolomics and gut microbiota correspond to clinical outcomes of reduced weight and inflammation and improved glucose and lipid metabolism.
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Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Humanos , Feminino , Glucose/farmacologia , Diabetes Mellitus Tipo 2/microbiologia , Metabolismo dos Lipídeos , RNA Ribossômico 16S , Hemoglobinas Glicadas , Dieta , Inflamação , Lipídeos/farmacologiaRESUMO
INTRODUCTION: Diffuse peripheral neuropathy is a well-known complication of several conditions, whereas many patients have peripheral neuropathy of unknown etiology and pathophyisology. Increased knowledge of mechanisms may provide insight into enteric neuropathy with gastrointestinal dysmotility. The aim of the present systematic review was to identify mechanisms behind diffuse idiopathic peripheral neuropathies in humans. METHODS: Searches were performed in PubMed, Embase, and Web of Science. Human original and review articles, written in English, describing mechanisms behind diffuse peripheral neuropathy verified by objective examinations were intended to be studied. Articles that described animal models, well-described hereditary diseases, drug-induced neuropathy, pain syndromes, malnutrition, and local neuropathy were excluded. RESULTS: In total, 4712 articles were identified. After scrutinizing titles and abstracts, 633 remained and were studied in full text. After the removal of articles not fulfilling inclusion or exclusion criteria, 52 were finally included in this review. The most frequently described neuropathy was diabetic neuropathy, with a wide range of mechanisms involving mitochondrial dysfunction such as oxidative stress and inflammation. Microvascular changes in diabetes and vasculitis lead to ischemia and secondary oxidative stress with inflammation. Structural changes in neurons and glial cells are observed, with abnormalities in different neurotrophic factors. Neuropathy induced by autoantibodies or immunological mechanisms is described in infectious and systemic inflammatory diseases. Several ion channels may be involved in painful neuropathy. No study identified why some patients mainly develop large fiber neuropathy and others small fiber neuropathy. CONCLUSION: Metabolic and immunological factors and channelopathy may be considered in diffuse idiopathic peripheral neuropathy.
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Neuropatias Diabéticas , Dor , Humanos , InflamaçãoRESUMO
BACKGROUND: The enteric nervous system (ENS) is situated along the entire gastrointestinal tract and is divided into myenteric and submucosal plexuses in the small and large intestines. The ENS consists of neurons, glial cells, and nerves assembled into ganglia, surrounded by telocytes, interstitial cells of Cajal, and connective tissue. Owing to the complex spatial organization of several interconnections with nerve fascicles, the ENS is difficult to examine in conventional histological sections of 3-5 µm. AIM: To examine human ileum full-thickness biopsies using X-ray phase-contrast nanotomography without prior staining to visualize the ENS. METHODS: Six patients were diagnosed with gastrointestinal dysmotility and neuropathy based on routine clinical and histopathological examinations. As controls, full-thickness biopsies were collected from healthy resection ileal regions after hemicolectomy for right colon malignancy. From the paraffin blocks, 4-µm thick sections were prepared and stained with hematoxylin and eosin for localization of the myenteric ganglia under a light microscope. A 1-mm punch biopsy (up to 1 cm in length) centered on the myenteric plexus was taken and placed into a Kapton® tube for mounting in the subsequent investigation. X-ray phase-contrast tomography was performed using two custom-designed laboratory setups with micrometer resolution for overview scanning. Subsequently, selected regions of interest were scanned at a synchrotron-based end-station, and high-resolution slices were reported. In total, more than 6000 virtual slices were analyzed from nine samples. RESULTS: In the overview scans, the general architecture and quality of the samples were studied, and the myenteric plexus was localized. High-resolution scans revealed details, including the ganglia, interganglional nerve fascicles, and surrounding tissue. The ganglia were irregular in shape and contained neurons and glial cells. Spindle-shaped cells with very thin cellular projections could be observed on the surface of the ganglia, which appeared to build a network. In the patients, there were no alterations in the general architecture of the myenteric ganglia. Nevertheless, several pathological changes were observed, including vacuolar degeneration, autophagic activity, the appearance of sequestosomes, chromatolysis, and apoptosis. Furthermore, possible expulsion of pyknotic neurons and defects in the covering cellular network could be observed in serial slices. These changes partly corresponded to previous light microscopy findings. CONCLUSION: The analysis of serial virtual slices could provide new information that cannot be obtained by classical light microscopy. The advantages, disadvantages, and future possibilities of this method are also discussed.
Assuntos
Sistema Nervoso Entérico , Plexo Mientérico , Sistema Nervoso Entérico/patologia , Amarelo de Eosina-(YS) , Hematoxilina , Humanos , Íleo/diagnóstico por imagem , Íleo/cirurgia , Parafina , Raios XRESUMO
OBJECTIVES: The prevalence of several autoimmune diseases, including thyroid dysfunction, has been reported to be increased in patients with endometriosis. Upregulated thyroid stimulation hormone (TSH) receptors in ectopic endometrium and elevated serum titers of TSH receptor antibodies (TRAb) IgG in endometriosis patients indicates an overlap in pathophysiology. However, cross-reactivity with other antibodies must be excluded. The objective of this study was to compare the expression of autoantibodies in women with endometriosis and two control groups to evaluate the potential of TRAb IgG as a diagnostic marker for endometriosis. STUDY DESIGN: This cross-sectional study was carried out in 172 women with surgically confirmed endometriosis and two control groups consisting of 50 healthy blood donors and 114 women from Malmö Offspring Study consisting of people from the general population. Serum levels of thyroid hormones, TSH and TRAb autoantibodies, AXIN1, and autoantibodies against follicle stimulating hormone (FSH), human chorionic gonadotropin (hCG), luteinizing hormone (LH), and their receptors, were analyzed. The patients answered a questionnaire and estimated their gastrointestinal symptoms using the Visual Analogue Scale for Irritable Bowel Syndrome. RESULTS: Of the endometriosis patients, 29.1â¯% had TRAb IgG above the present detection limit ofâ¯≥â¯1.0â¯IE/L compared to 2.6â¯% of the controls from MOS (pâ¯<â¯0.001) and 94.5â¯% had levels of TRAb over the previous detection limitâ¯≥â¯0.3â¯IE/L compared to 7.9â¯% of the controls (pâ¯<â¯0.001). Titers of both TRAb IgG and IgM were increased in patients compared to controls from MOS and blood donors, respectively (pâ¯<â¯0.001). There was no increase of autoantibodies against FSH, FSH receptor (FSHR), hCG, LH, LH receptor (LHR) or TSH compared to the blood donor controls. TRAb titers did not correlate with age, disease duration, AXIN1, TSH, thyroid hormones or gastrointestinal symptoms. CONCLUSION: TRAb IgG and IgM are slightly elevated in patients with endometriosis with no cross-reactivity with other autoantibodies. The results indicate that TRAb is truly elevated and thereby has the potential to be used to support the diagnosing of endometriosis.
Assuntos
Endometriose , Receptores da Tireotropina , Humanos , Feminino , Receptores do FSH/metabolismo , Receptores do LH/metabolismo , Endometriose/diagnóstico , Estudos Transversais , Autoanticorpos , Imunoglobulina G , Hormônio Foliculoestimulante , Biomarcadores , Gonadotropina Coriônica , Tireotropina , Imunoglobulina M , Hormônio LuteinizanteRESUMO
Background: Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits. Further, IBS patients experience a high degree of extraintestinal symptoms. Objectives: The aim of this review was to describe the relation between IBS and extraintestinal manifestations and mechanisms and treatments of these extraintestinal manifestations. Design: The study was performed as a systematic review. Data Sources and Methods: Search terms including extraintestinal manifestations or somatization and IBS were used to scrutinize for publications in Pubmed. In total, 630 publications were identified and 80 were finally included in this review. Results: About 50% of all IBS patients have extraintestinal manifestations in addition to gastrointestinal symptoms. Somatic pain, fatigue, and sleeping disturbances are most common, and most often described in women. Both extraintestinal manifestations and psychological distress are associated with exaggerated gastrointestinal symptoms, impaired quality of life, and difficulties to treat IBS symptoms. The extraintestinal manifestations render an excess of healthcare costs. Varying etiology and pathophysiology to IBS are discussed, and many patients express a general hypersensitivity. Extraintestinal symptoms are seldom documented at clinical healthcare or included in the assessment of treatment outcomes. A good patient-physician relationship and strengthening of coping mechanisms have rendered less gastrointestinal symptoms, psychological distress, and somatization. Altered lifestyle habits may improve both gastrointestinal and extraintestinal symptoms. Pharmacological treatment, including antidepressant drugs, should be considered when lifestyle advice fails. Teamwork between different specialists and healthcare providers may be of importance in the wide range of symptoms and extraintestinal manifestations. Conclusion: Extraintestinal manifestations are common in IBS patients and is associated with worse suffering and difficulties to treat symptoms. Evaluation and treatment of IBS patients should consider also extraintestinal manifestations and their treatment outcome. Establishment of good relationship, strengthening of coping mechanisms, and education in healthier lifestyle habits are crucial in the management of these patients.
RESUMO
BACKGROUND: Risk prediction is an essential part of preventative medicine and in recent years genomic information has become an interesting factor in risk models. Polygenic risk scores (PRS) combine the effect of many genetic variations into a single score which has been shown to have predictive value for many diseases. This study aimed to investigate the association between PRS for endometriosis and the clinical presentation of the disease. METHODS: Women with endometriosis (N = 172) were identified at the Department of Gynecology. All participants answered questionnaires regarding sociodemographic factors, lifestyle habits and medical history, registered bowel symptoms on the Visual Analog Scale for Irritable Bowel Syndrome and passed blood samples. DNA was extracted and samples were genotyped, and a PRS was calculated based on previous genome-wide association studies of endometriosis. Inflammatory proteins and TSH receptor antibodies (TRAb) in serum were analyzed. RESULTS: Inverse associations were identified between PRS and spread of endometriosis, involvement of the gastrointestinal tract and hormone treatment. However, significance was lost when calculated as p for trend and the specificity and sensitivity were low. There were no correlations between PRS and TRAb or inflammatory proteins. CONCLUSION: The findings indicate that specific PRS should be developed to predict clinical presentations in patient with endometriosis.