Identification of Presurgical Risk Factors for the Development of Chronic Postsurgical Pain in Adults: A Comprehensive Umbrella Review.

Purpose: Risk factors for the development of chronic postsurgical pain (CPSP) have been reported in primary studies and an increasing number of reviews. The objective of this umbrella review was to compile and understand the published presurgical risk factors associated with the development of CPSP for various surgery types. Methods: Six databases were searched from January 2000 to June 2023 to identify meta-analyses, scoping studies, and systematic reviews investigating presurgical CPSP predictors in adult patients. Articles were screened by title/abstract and subsequently by full text by two independent reviewers. The selected papers were appraised for their scientific quality and validity. Data were extracted and descriptively analyzed. Results: Of the 2344 retrieved articles, 36 reviews were selected for in-depth scrutiny. The number of primary studies in these reviews ranged from 4 to 317. The surgery types assessed were arthroplasty (n = 13), spine surgery (n = 8), breast surgery (n = 4), shoulder surgery (n = 2), thoracic surgery (n = 2), and carpal tunnel syndrome (n = 1). One review included a range of orthopedic surgeries; six reviews included a variety of surgeries. A total of 39 presurgical risk factors were identified, some of which shared the same defining tool. Risk factors were themed into six broad categories: psychological, pain-related, health-related, social/lifestyle-related, demographic, and genetic. The strength of evidence for risk factors was inconsistent across different reviews and, in some cases, conflicting. A consistently high level of evidence was found for preoperative pain, depression, anxiety, and pain catastrophizing. Conclusion: This umbrella review identified a large number of presurgical risk factors which have been suggested to be associated with the development of CPSP after various surgeries. The identification of presurgical risk factors is crucial for the development of screening tools to predict CPSP. Our findings will aid in designing screening tools to better identify patients at risk of developing CPSP and inform strategies for prevention and treatment.

Chronic postsurgical pain (CPSP) is pain experienced predominantly at the surgical site for longer than 3 months after a surgical procedure. Depending on surgery type, it can affect between 10 and 80% of people undergoing major surgeries, which may have negative effects such as a lower quality of life, disability, and persistent opioid use. Targeted identification and management of at risk patients in the presurgical phase may decrease the risk of CPSP. This umbrella review generated a list of potential risk factors for CPSP from evidence-based reviews of the current literature. Thirty-nine presurgical risk factors were identified in this review. Risk factors are divided into six broad categories: psychological, pain-related, health-related, demographic, genetic, and social/lifestyle-related. Although the strength of evidence for individual risk factors varied across reviews, risk factors in the psychological category consistently showed a strong impact on the development of CPSP. It is vital to understand which individuals are vulnerable and at risk for CPSP. The findings of this umbrella review will aid in designing screening tools to identify surgical candidates at risk. Some risk factors, such as genetics, cannot be altered. However, many identified risk factors are modifiable and may inform strategies for the prevention and treatment of CPSP using screening tools. Our findings may guide future research to consider an in-depth analysis of risk factor characterization to group modifiable presurgical risk factors. At risk patients will be offered psychological, physical, and pharmacological treatments accordingly to mitigate their risk of developing CPSP and ultimately improve patient outcomes in surgery.

Challenges in diagnosis and health care in polycystic ovary syndrome in Canada: a patient view to improve health care.

BACKGROUND: Polycystic Ovary Syndrome (PCOS) is the most common endocrine-metabolic disorder affecting health and quality of life of those affected across the lifespan. We currently have limited evidence-based data on the experience of those living with PCOS in the health care system including diagnosis, health concerns and disease management. The aim of this study was to assess the perceptions of health status, health care experience and disease management support in those affected by PCOS in Alberta, Canada. METHODS: An online questionnaire was completed via REDCap by individuals self-reporting a diagnosis of PCOS. Question categories included demographics, symptoms of PCOS and time to confirm a diagnosis, follow-up care, health concerns, and information resources. Descriptive statistics were used and thematic analyses was applied to open-response questions. RESULTS: Responses from 194 participants living in Canada (93% in Alberta) were included. The average age was 34 ± 8 years and BMI was 35 ± 9. Menstrual irregularity was identified in 84% of respondents as the first symptom noticed and the primary reason for seeking a medical consultation. A PCOS diagnosis occurred on average 4.3 years following awareness of first symptoms and required consultation with more than one primary care provider for 57% of respondents. Half (53%) of respondents reported not receiving a referral to specialists for follow-up care and 70% were not informed about long-term health morbidity such as diabetes or cardiovascular disease. Most respondents (82%) did their own research about PCOS using on-line sources, academic literature and advice from peer support. The participant themes from open questions for improving health care included more resources and support, increased and reliable information, better education and training for clinicians, timely diagnosis, prompt referrals to specialists, and generally more compassion and empathy to the challenges faced by those managing their disease. CONCLUSION: Our findings highlight the health concerns and challenges in health care for those with PCOS. In Alberta, Canada we have identified major gaps in health care including a timely diagnosis, follow up care and supports, and multidisciplinary care. This evidence-based data can be used to inform development of pathways to improve the health care experience in those affected by PCOS.

Assessing young adults' menopause knowledge to increase understanding of symptoms and help improve quality of life for women going through menopause; a student survey.

BACKGROUND: Due to menopause being a largely invisible and under-discussed topic in wider society, women often deal with menopause-related complications on their own. Social support and awareness have been shown to reduce negative menopausal experiences; however, lack of menopause knowledge, particularly among younger people, may deter support for women suffering from menopause symptoms. This study aims to assess the level of knowledge young adults have on menopause to be able to create interventions that target knowledge gaps and increase understanding of women's experiences and difficulties during their menopause transition. METHODS: We created an electronic questionnaire based on menopause literature and guidelines from Menopause Societies. It was pilot-tested on young people in the target group age (n = 14; 7 male and 7 female), menopause clinicians (n = 5), and women experiencing menopause (n = 4). The final survey included questions on participant demographics, general menopause knowledge, and options to support menopause management and was distributed through university student newsletters. Responses over a two week period were collected anonymously. Descriptive statistics were applied to characterize participants, define menopause knowledge, and identify gaps. Chi-squared statistics was used for group comparison, and open questions were analyzed using qualitative content analysis. RESULTS: Survey responses were collected from 828 students; the average age was 22.1 ± 5.1 and 83.6% were female. Participants belonged to all faculties and included students from a variety of family settings and living conditions. Knowledge questions revealed a good understanding of the basic menopause physiology for most respondents, but there were gaps in understanding of symptoms and symptom management. Female sex and personal connection to menopausal women had a positive effect on the degree of menopause knowledge. Both males and females reported increased knowledge confidence at the end of the survey. CONCLUSION: Our survey provides evidence that young adults of both sexes have a general baseline knowledge of menopause and its symptoms and are open to learning strategies to help support menopausal women. Our findings will assist in developing targeted educational resources to increase social support and awareness, reduce stigma and improve the quality of life for menopausal women, and help prepare younger women for their future menopause journey.

Does the Type of Surgical Headwear Worn in the OR Matter? A Review of Evidence and Opinions.

Proper surgical attire is essential in decreasing surgical site infections; however, the effectiveness of the different types of headwear is a controversial topic. We conducted a narrative review based on studies identified through a focused literature search to summarize and critically assess evidence and opinions on the most appropriate type of headwear for OR personnel. We included 48 articles: 17 original research studies and 31 non-peer-reviewed articles of various types. Research published before 2014 mostly supports the complete coverage of all hair, which aligns with the 2015 AORN guidelines. However, more recent literature rebuts these guidelines and emphasizes the importance of clean headwear. Although earlier studies (published before 2017) lacked scientific rigor, later studies (published after 2017) have other various limitations, including missing data on compliance, surgery-related techniques, and surgical attire other than headwear. The findings from this review highlight the importance of solid evidence-based guidelines and expert collaboration.

Traditional crafting as a catalyst for Indigenous women's intergenerational cohesion and wellness: a Canadian perspective.

Indigenous crafting practices are increasingly being recognised for their benefit to community connectedness, health, cultural identity, and individual wellbeing. This article explores published literature to determine the role of Indigenous crafting in transferring traditional and cultural teachings from female relatives and Elders to girls and younger women. We examine the effect of crafting on intergenerational cohesion and social connectedness within the Indigenous community. Does crafting serve as an effective conduit for physical, spiritual, emotional, and mental change in learners and teachers? Our review identifies 12 publications that describe Indigenous mostly girls and younger women's experiences as they acquire female Elders', teachers' and older family members' traditional and cultural teachings while participating in crafting activities. The papers identify an array of traditional and cultural activities including: basket weaving, beading, sewing, language acquisition, traditional songs, traditional dance, and storytelling. More contemporary forms of artistic expression such as photography, theatre and film production are also included. Research findings show that learning, teaching and practicing Indigenous crafting is associated with increased intergenerational cohesion, cultural connectedness, and wellbeing for both teachers and learners. Further, learning about Indigenous crafts and activities helps inspire pride in Indigenous identity and promotes healing from historical trauma.

Indigenous gender and wellness: a scoping review of Canadian research.

This scoping review examined research publications related to health and/or wellness along with gender among Canadian Indigenous populations. The intent was to explore the range of articles on this topic and to identify methods for improving gender-related health and wellness research among Indigenous peoples. Six research databases were searched up to 1 February 2021. The final selection of 155 publications represented empirical research conducted in Canada, included Indigenous populations, investigated health and/or wellness topics and focused on gender. Among the diverse range of health and wellness topics, most publications focused on physical health issues, primarily regarding perinatal care and HIV- and HPV-related issues. Gender diverse people were seldom included in the reviewed publications. Sex and gender were typically used interchangeably. Most authors recommended that Indigenous knowledge and culture be integrated into health programmes and further research. More health research with Indigenous peoples must be conducted in ways that discern sex from gender, uplift the strengths of Indigenous peoples and communities, privilege community perspectives, and attend to gender diversity; using methods that avoid replicating colonialism, promote action, change stories of deficit, and build on what we already know about gender as a critical social determinant of health.

Menopause experience in First Nations women and initiatives for menopause symptom awareness; a community-based participatory research approach.

BACKGROUND: Little research has been conducted about menopause in First Nations women. In response to the wishes of Cree women living in Maskwacis, Alberta, to start a dialogue on menopause, we undertook community-based participatory research (CBPR) to explore menopause experience and raise awareness of menopause symptoms in the community. METHODS: The research adhered to the principles of Ownership, Control, Access and Possession (OCAP™) and was guided by the interest of the participating women. Local women (target age 40-65 years) were invited to participate in workshops using word-of-mouth and community posters in health centers. Five research workshops were held in community settings, attended by experienced women's health researchers and consenting women. The participants guided the informal discussions. They also completed questionnaires which included menopause-related quality of life. The researchers used extensive hand-written field notes to record data; qualitative content analysis was applied to identify themes. Simple descriptive analysis was used for the questionnaire results. The findings were discussed at a community feedback session and laid the basis for further knowledge translation initiatives. RESULTS: The five workshops included a total of 37, mostly post-menopausal women with 6-11 women/workshop. The main discussion themes were: "experiences of menopause symptoms" including their impact on quality of life; "menopause knowledge prior to their own experience" with most women feeling that they had insufficient information before menopause; "menopause symptom management" which mainly included practical strategies; "impact of menopause on family members" which was of prime concern with uncontrollable mood changes affecting the whole family and sometimes causing matrimonial disharmony. Questionnaire responses corroborated the workshop discussions. Knowledge translation of the research findings produced two information pamphlets specifically for the Maskwacis community: one for husband/partner, the other for women and family members. These pamphlets have been distributed in all areas of the community. CONCLUSION: This CBPR project addressed a topic identified by the community as being important. Community members developed informative pamphlets in response to the women's concern of lack of understanding for menopause symptoms among families. This simple solution has been widely accepted by community members, opening the possibility of wider discussion about menopause.

Contraception Use and Attitudes Among Women Seeking Pregnancy Termination: Descriptive Cross-Sectional Survey.

OBJECTIVE: Unintended pregnancy has been linked to poor health and social outcomes for both mother and child. Efforts to reduce unintended pregnancies have been challenged by many financial, social, religious, and cultural factors. This study aimed to investigate how contraception use and misuse in a cohort of females seeking termination of pregnancy contribute to unintended pregnancies. METHODS: We conducted a cross-sectional study with women presenting to a women's health clinic for pregnancy termination from April to December 2017. Consenting participants completed a self-administered, confidential questionnaire that included questions on demographic, ethnic, and social characteristics, as well as behaviours and attitudes related to contraception. Data analysis used descriptive statistics. RESULTS: Data were collected from 334 women; about half (45%) had used contraception at the time of conception, representing a variety of different methods. Contraceptive use was associated with higher education, stable relationship status, and ethnic majority status but not with previous pregnancies or immigration status. Among contraceptive users, imperfect and inconsistent use of contraception (50% and 31%, respectively), and method failure (48%), including condom breakage, were cited as reasons for the current pregnancy. Non-users reported perceived low risk of pregnancy (55%), concerns about contraception (47%), and problems accessing contraception (27%). While the majority of participants were aware of emergency contraception, only 52% reported ever using it. Most participants (89%) planned to use contraception in the future. CONCLUSION: Our study highlights contraceptive behaviours and patterns of individuals seeking abortion. Patient-centered contraceptive counselling in order to facilitate contraceptive choice and access can include information about the most effective contraceptives and the need for back-up contraception methods.

Walking together: women with the severe symptoms of menopause propose a platform for a walking program; outcome from focus groups.

BACKGROUND: Menopause and midlife are stages in a woman's life that can be marked by debilitating symptoms and increasing risks for cancer, cardiovascular, metabolic, and bone health issues. Walking represents a simple, low cost, and widely accessible activity with proven health benefits, though its therapeutic effect on alleviating menopause symptoms is not well characterized. Women are generally not opposed to exercise programs; however, increasing or maintaining exercise levels remains a challenge. We undertook a qualitative descriptive study to explore features of a walking program that would be conductive to menopausal women's participation, as well as to inform the development of such a program. METHODS: We conducted focus groups with women recruited from two menopause clinics and who suffered from moderate to severe menopause symptoms. The focus groups were audio recorded and transcribed. Women were prompted to talk about their menopause experience and exercise practice and how they would envision a walking exercise program that would keep them engaged. Qualitative content analysis was used to analyze the data and to identify characteristics of a walking exercise program. RESULTS: Twenty women participated in 5 focus groups. Women were very interested in trying walking as a means of staying healthy and possibly reducing menopause symptoms. Four major characteristics emerged as important for a walking program: (a) sensitivity to health realities of menopausal women, (b) inclusivity of various needs/levels of physical ability, (c) attentiveness to the need for mutual social support, (d) flexibility in planning of locations and scheduling. A restricted social network platform with features catering to women in menopause was suggested as suitable to initiate and sustain an adequate walking program. CONCLUSIONS: The findings of this study will be essential in designing a program that would be attractive for women to start and maintain a walking habit. The program would assist in elucidating whether walking is a useful and valuable alternative therapy for menopausal symptoms and, ultimately, might help women staying fit in midlife and postmenopausal.

Can walking exercise programs improve health for women in menopause transition and postmenopausal? Findings from a scoping review.

OBJECTIVE: Our goal was to explore the range and characteristics of published papers on therapeutic walking programs for menopausal women and to identify program features that resulted in successful outcomes including reduced symptoms and improved long-term wellness. METHODS: We searched biomedical and exercise-related databases for articles published up to June 1, 2017, using keywords related to menopause and walking. Data were collected into EndNote X8 reference manager to identify and remove duplicates. The final selection included all articles that studied walking as a health intervention for women in menopause transition or postmenopausal. RESULTS: A total of 3,244 papers were collected from the six databases. After removing duplicates and applying inclusion and exclusion criteria, 96 articles were charted, including 77 different walking programs. Walking interventions ranged from 4 weeks to 3 years with an average weekly frequency of 3.8 ±â€Š1.8 and were applied to a variety of symptoms and their biological markers and risk factors. Overall, 91% of the programs showed a beneficial outcome in at least one menopause-related medical issue. Information on menopause-specific symptoms, especially vasomotor symptoms and sleep problems, was scarce. CONCLUSION: The scoping review highlights the growing interest in walking programs as therapies for menopause and related symptoms and provides evidence of their possible benefit as a wellness option for women in menopause and beyond. Further research would be recommended to establish the therapeutic value of walking programs for women with specific focus on typical menopause symptoms at different stages of menopause. : Video Summary:http://links.lww.com/MENO/A587.

Video Summary:http://links.lww.com/MENO/A587.

Change over time in patient-reported symptoms and quality of life in Edmonton interdisciplinary menopause clinics: preliminary cohort study of clinic patients and waitlist patients.

OBJECTIVE: Specialized interdisciplinary menopause clinics in Edmonton provide care for women suffering from severe menopausal symptoms. Our objectives were to evaluate changes over time in patient-reported menopause symptoms and quality of life (QOL) in a cohort of clinic patients, compared to a cohort of women recruited from the clinic waitlists. METHODS: We conducted a prospective study of consecutive new patients in two clinics. Consenting women completed a generic menopause symptom severity questionnaire (MSSQ) and the menopause-specific quality of life (MENQOL) questionnaire at their first clinic and at a follow-up visit. Demographics, medical and obstetric histories, and medication use were extracted from patient charts. Women on the clinics' waitlists were enrolled as controls; corresponding data for baseline and follow-up were collected in mailed-in surveys. Descriptive and paired statistics were used for data analysis. Agreement plot was created to visualize the agreement between MSSQ and MENQOL scores. RESULTS: A total of 139 women were recruited: 98 attended the clinic and 41 were from the waitlist. Follow-up data were available for 99 women (71 clinic and 28 waitlist). There were no significant differences between clinic and waitlist patient characteristics. Women attending the clinics experienced significant reduction in symptom severity (mean MSSQ scores) and improvement in QOL (reduced MENQOL "bother" scores). Women on the clinic waitlist did not demonstrate significant changes over a similar timeframe. MENQOL correlated well with menopause symptom severity assessment. CONCLUSION: Women attending specialized menopause clinics experienced improvement in symptoms and QOL, whereas women on the waitlists did not experience these changes. : Video Summary: Supplemental Digital Content 1, http://links.lww.com/MENO/A418.

Patient characteristics, menopause symptoms, and care provided at an interdisciplinary menopause clinic: retrospective chart review.

OBJECTIVE: The goal of this study was to describe the characteristics, menopause symptoms, and treatment progressions in women cared for at an interdisciplinary menopause clinic. METHODS: We conducted a retrospective review of patient charts from women attending a multidisciplinary menopause clinic. Data collected from the charts included patient demographics, menopause symptoms, other concurrent medical conditions, and treatment recommendations. Data were entered into Research Electronic Data Capture database and analyzed descriptively. Generic symptom severity questionnaires were used to compare severity scores from initial to follow-up visits. RESULTS: Among the 198 women (mean age 52.1 y [±SD 6.3], 63.6% postmenopausal), the most common moderate/severe menopause symptoms were as follows: difficulty staying asleep or waking frequently (76.3%), tiredness (73.7%), and lack of interest in sex (60.1%). Women tended to have complex chronic medical conditions, with 54.5% suffering from four or more concurrent medical conditions. The majority of women (70.2%) were recommended various forms of hormone therapy. Women with a follow-up visit at 3 to 4 months reported a reduction in symptom severity. CONCLUSIONS: Our study addresses a gap in published information on patient characteristics and treatment in menopause-specific interdisciplinary clinics. The chart review highlights the variety of symptom experience and complexity of care faced in a menopause clinic. Rigorous prospective studies including standardized data collection and follow-up are needed to help guide clinicians in managing complex menopause patients.

Use of the Menopause-Specific Quality of Life (MENQOL) questionnaire in research and clinical practice: a comprehensive scoping review.

OBJECTIVE: The Menopause-Specific Quality of Life (MENQOL) questionnaire was developed as a validated research tool to measure condition-specific QOL in early postmenopausal women. We conducted a comprehensive scoping review to explore the extent of MENQOL's use in research and clinical practice to assess its value in providing effective, adequate, and comparable participant assessment information. METHODS: Thirteen biomedical and clinical databases were systematically searched with "menqol" as a search term to find articles using MENQOL or its validated derivative MENQOL-Intervention as investigative or clinical tools from 1996 to November 2014 inclusive. Review articles, conference abstracts, proceedings, dissertations, and incomplete trials were excluded. Additional articles were collected from references within key articles. Three independent reviewers extracted data reflecting study design, intervention, sample characteristics, MENQOL questionnaire version, modifications and language, recall period, and analysis detail. Data analyses included categorization and descriptive statistics. RESULTS: The review included 220 eligible papers of various study designs, covering 39 countries worldwide and using MENQOL translated into more than 25 languages. A variety of modifications to the original questionnaire were identified, including omission or addition of items and alterations to the validated methodological analysis. No papers were found that described MENQOL's use in clinical practice. CONCLUSIONS: Our study found an extensive and steadily increasing use of MENQOL in clinical and epidemiological research over 18 years postpublication. Our results stress the importance of proper reporting and validation of translations and variations to ensure outcome comparison and transparency of MENQOL's use. The value of MENQOL in clinical practice remains unknown.

A survey of the availability in Canadian pharmacy chains of over-the-counter natural health products for menopause symptoms.

BACKGROUND: Menopause is a natural phase in a woman's aging process, characterized by the cessation of menstruation. Women who are going through the menopause transition can experience physiological symptoms that significantly impact their quality of life. Concern about adverse effects of traditional hormone therapy often leads women to purchase over-the-counter (OTC) natural health products (NHPs). The goal of this study was toinvestigate the range of OTC NHPs for menopause available to Canadian women, and the packaging information they can access to make self-management decisions. METHODS: Edmonton stores belonging to each of nine Canadian pharmacy chains were visited to identify NHPs marketed for the relief of menopausal symptoms. Details were extracted from the packaging: a) product name and manufacturer, b) Health Canada license number, c) medically active ingredients, d) claims of efficacy, e) contra-indications and warnings, and f) daily cost. Data were entered and analyzed using Microsoft Excel. RESULTS: We identified 20 OTC NHP menopausal products, 19 of which had Health Canada license numbers. Twenty-eight medically active ingredients were identified, with the most common being black cohosh (in 14 products) and soy isoflavones (n = 7), chaste tree (n = 5), and dong quai (n = 3). Most products claimed they would relieve vasomotor symptoms, including hot flashes (n = 14) and night sweats (n = 10). Each product had a labeled contraindication for at least one specific condition. Costs per recommended daily dose ranged from $0.07 to a maximum of $2.50 (CAD$). CONCLUSION: Natural health products for menopausal symptoms are easily available to Canadian women. The lack of clear evidence of product efficacy makes the need for easily accessible, balanced information on this topic important for women to make well informed choices.

Metabolomic profiles are gender, disease and time specific in the interleukin-10 gene-deficient mouse model of inflammatory bowel disease.

Metabolomic profiling can be used to study disease-induced changes in inflammatory bowel diseases (IBD). The aim of this study was to investigate the difference in the metabolomic profile of males and females as they developed IBD. Using the IL-10 gene-deficient mouse model of IBD and wild-type mice, urine at age 4, 6, 8, 12, 16, and 20 weeks was collected and analyzed by nuclear magnetic resonance (NMR) spectroscopy. Multivariate data analysis was employed to assess differences in metabolomic profiles that occurred as a consequence of IBD development and severity (at week 20). These changes were contrasted to those that occurred as a consequence of gender. Our results demonstrate that both IL-10 gene-deficient and wild-type mice exhibit gender-related changes in urinary metabolomic profile over time. Some male-female separating metabolites are common to both IL-10 gene-deficient and control wild-type mice and, therefore, appear to be related predominantly to gender maturation. In addition, we were able to identify gender-separating metabolites that are unique for IL-10 gene-deficient and wild-type mice and, therefore, may be indicative of a gender-specific involvement in the development and severity of the intestinal inflammation. The comparison of the gender-separating metabolomic profile from IL-10 gene-deficient mice and wild-type mice during the development of IBD allowed us to identify changes in profile patterns that appear to be imperative in the development of intestinal inflammation, but yet central to gender-related differences in IBD development. The knowledge of metabolomic profile differences by gender and by disease severity has potential clinical implications in the design of both biomarkers of disease as well as the development of optimal therapies.

Small bowel fibrosis and systemic inflammatory response after ileocolonic anastomosis in IL-10 null mice.

BACKGROUND: Crohn's disease recurrence after an ileocecal resection is common; yet, its pathophysiology is poorly understood and available treatment is suboptimal. The purpose of this study was to examine the bacterial, local, and systemic immune changes that follow ileocolonic anastomosis in a rodent model of Crohn's disease, the interleukin-10 gene-deficient (IL-10 null) mice. MATERIALS AND METHODS: We divided wild-type and IL-10 null mice into three treatment groups: ileocolonic anastomosis, sham operation (ileo-ileal anastomosis), and control group without an operation. We sacrificed mice at 6 and 15 wks after the operation. At 6 wks, we assessed bacterial changes using the denaturing gel electrophoresis and similarity coefficient calculation. At both time points, we examined the small bowel for inflammation and fibrosis with histology. We measured the interferon gamma secretion by splenocytes stimulated with gastrointestinal bacterial antigens and splenocyte composition as a marker of systemic response. RESULTS: At 6 wks, ileocolonic anastomosis resulted in increased similarity in bacterial species between the ileum and colon. The ileocolonic anastomosis did not lead to significant inflammation in the small intestine, but it resulted in an increased collagen deposition in all animals undergoing surgery, the most pronounced fibrosis of which was present in IL-10 null mice 15 wks after ileocolonic anastomosis. Furthermore, this was associated with significantly increased interferon gamma secretion by bacterial antigen-stimulated splenocytes and a decreased number of CD11+ cells in the same experimental group. CONCLUSIONS: Ileocolonic anastomosis leads to bacterial changes in the terminal ileum. In the genetically susceptible host, it is associated with small bowel fibrosis and systemic immune alterations. The composition of immune cells in the spleen is altered and splenocytes hypersecrete proinflammatory cytokine (interferon gamma) when challenged with gastrointestinal bacterial antigens.

Validation of a point-of-care desk top device to quantitate fecal calprotectin and distinguish inflammatory bowel disease from irritable bowel syndrome.

BACKGROUND AND AIMS: The neutrophil protein calprotectin has been investigated as a surrogate marker for intestinal inflammation. This study was designed to contrast fecal calprotectin levels in patients with inflammatory and non-inflammatory intestinal diseases and to compare the results obtained from the standard ELISA-based method with those obtained from a novel desk-top device. METHODS: Soluble proteins were extracted from stool samples of 50 participating patients, including those diagnosed with Ulcerative Colitis, Crohn's Disease or IBS, and volunteers with no known intestinal problems. Calprotectin was assessed in the extracted material using the "desk top" Bühlmann Quantum Blue Reader® or by standard ELISA techniques. RESULTS: The mean concentration of calprotectin in the IBD patients group was significantly higher than the mean concentration found in IBS patients and healthy controls (p=0.01). Calprotectin concentrations in IBS patients and controls were indistinguishable. IBD patients that had undergone recent surgery displayed scores similar to controls and IBS patients. Excluding these patients yielded a specificity of 100% for results from both CD and UC patients and an accuracy rate of 1 for CD and 0.89 for UC patients in ROC analysis. Quantum Blue Reader® calprotectin levels were available within 30 min and correlated well with results derived from standard ELISA assays, which took over 8h to complete. CONCLUSION: Our results confirm the effective use of fecal calprotectin levels in differentiating non-inflammatory from active inflammatory intestinal diseases. The desk top Bühlmann Quantum Blue Reader® exhibits a fast, non-invasive, and reliable way of identifying an inflammatory intestinal disease.

Intravenous injection of endogenous microbial components abrogates DSS-induced colitis.

BACKGROUND: The etiology of inflammatory bowel diseases (IBD) is largely unknown, but appears to be perpetuated by uncontrolled responses to antigenic components of the endogenous flora. Tolerance to antigenic stimulation can be achieved by exposure to a given antigen in high amounts (high dose tolerance). Colitis induced by feeding of Dextran Sodium Sulfate (DSS) is an often-used animal model mimicking clinical and histological features of human IBD. AIMS: We investigated whether treatment with high doses of endogenous bacterial components can affect the response to these antigenic components and thus impact the course of the inflammatory response induced by DSS. METHODS: 129/SvEv mice were injected intravenously in the tail vein with lysates prepared from fecal material of conventionally-raised mice. Control mice received a solution of bacterial antigen-free lysates prepared from fecal material of germ-free mice. Seven days later, colitis was induced in these mice by introducing DSS (3.5%) in the drinking water for 5 days. Onset and course of the inflammatory response was monitored by assessment of weight loss. Mice were sacrificed at day 7 post colitis induction and tested for histopathologic injury, intestinal cytokine release, and systemic response to bacterial antigens. RESULTS: Intravenous injection with fecal lysates reduced intestinal and antigen-stimulated systemic pro-inflammatory cytokine release and prevented DSS-induced weight loss and intestinal injury. CONCLUSION: Pretreatment with high amount of endogenous bacterial components has a profound tolerogenic effect on the systemic and mucosal immune responses resulting in reduced intestinal inflammation and abrogates colitis-induced weight loss.

Neonatal exposure to fecal antigens reduces intestinal inflammation.

BACKGROUND: A role for bacterial antigens in the pathogenesis of inflammatory bowel disease (IBD) has been established in enhanced humoral and cellular immune response to ubiquitous antigens of the enteric flora. However, we have recently shown that bacterial antigens in the absence of live bacteria cannot initiate an intestinal inflammation in IBD-prone interleukin (IL)-10 gene-deficient mice. The objective was to investigate whether neonatal exposure to antigens of their own endogenous flora can tolerize mice to bacterial antigens. METHODS: IL-10 gene-deficient neonates were injected intraperitoneally within 72 hours of birth with a sterile solution of bacterial lysates prepared from fecal material of either conventionally raised mice (contains bacterial antigens) or axenic mice (lacks bacterial antigens). The onset of intestinal inflammation was monitored as the appearance of occult blood in the stool in weekly hemoccult analysis. Mice were sacrificed between age 15 and 19 weeks and tested for histopathologic injury, intestinal inflammation, and systemic response to bacterial antigens. RESULTS: In mice neonatally exposed to bacterial antigens the onset of intestinal inflammation was delayed and the incidence of histopathologic injury at age 18 weeks was reduced. In addition, mice injected with lysates from conventionally raised mice exhibited decreased release of proinflammatory cytokines (interferon gamma [IFN-γ] and IL-17) in intestinal tissue and demonstrated reduced bacteria-stimulated systemic responses when compared to mice injected with lysates derived from bacteria-free, axenic mice. CONCLUSIONS: Neonatal intraperitoneal injection of antigens from the commensal flora causes long-lasting changes in systemic and mucosal immune responses resulting in delayed onset of intestinal inflammation and injury in IBD-prone IL-10 gene-deficient mice.