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Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy.
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Wrist Mycobacterium tuberculosis (TB) complex osteomyelitis is rare, with polymicrobial TB osteomyelitis even more uncommon. The authors describe an unusual case of polymicrobial TB wrist osteomyelitis. The case patient presented with a 2.5-year history of 2 insidiously growing nodules on his wrist. He underwent debridement, and tissue cultures grew methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, and, later, TB complex. He was started on vancomycin, rifampin, isoniazid, pyrazinamide, and ethambutol with improvement in symptoms. This case emphasizes the importance of a broad differential and thorough workup for atypical presentations of osteomyelitis. Diagnosis of uncommon etiologies is essential for definitive treatment.
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OBJECTIVE: To explore the mental health experiences of adolescents and young adults (AYA) with inflammatory bowel disease (IBD) enrolled in a randomized controlled trial evaluating the impact of a multimodal transition intervention. STUDY DESIGN: Virtual semistructured interviews were held with 21 AYA aged 16 through 18 years with IBD. Guided by qualitative description, interviews were digitally recorded, transcribed verbatim, and analyzed using an inductive approach to reflexive thematic analysis. RESULTS: Three themes were generated from the data: (1) a continuum of integration between IBD and personal identity in adolescence and young adulthood; (2) manifestations of the mind-gut connection among AYA with IBD; and (3) hopes and priorities for addressing mental health in IBD care. CONCLUSIONS: AYA with IBD endorsed the criticality of incorporating mental health discussions into routine care during the transition to adult care, given the co-occurrence of psychosocial stressors throughout this period. A series of factors promoting and hindering the integration of IBD into one's identity were identified and could be explored in clinical encounters.
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Refractory Crohn's disease, defined as ongoing inflammation despite the trial of multiple advanced therapies, impacts a number of individuals with Crohn's disease, and leads to significant burden in quality of life and cost. Interventions such as early implementation of advanced therapies, optimization of current therapies prior to switching to an alternative, as well as understanding the overlapping pathophysiology between immune-mediated disorders, however, can help shift the current landscape and reduce the number of patients with refractory disease. As such, in this review we summarize the key takeaways of the latest research in the management of moderate-to-severe Crohn's disease, focusing on maximization of our currently available medications, while also exploring topics such as combination advanced therapies. We also describe evidence for emerging and alternative therapeutic modalities, including fecal microbiota transplant, exclusive enteral feeding, hyperbaric oxygen, stem cell therapy, bone marrow transplant, and posaconazole, with a focus on both the potential impact and specific indications for each.
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Endometrial cancer, the most common gynaecological cancer worldwide, is closely linked to obesity and metabolic diseases, particularly in younger women. New circulating biomarkers have the potential to improve diagnosis and treatment selections, which could significantly improve outcomes. Our approach focuses on extracellular vesicle (EV) biomarker discovery by directly profiling the proteome of EVs enriched from frozen biobanked endometrial tumours. We analysed nine tissue samples to compare three clinical subgroups-low BMI (Body Mass Index) Endometrioid, high BMI Endometrioid, and Serous (any BMI)-identifying proteins related to histological subtype, BMI, and shared secreted proteins. Using collagenase digestion and size exclusion chromatography, we successfully enriched generous quantities of EVs (range 204.8-1291.0 µg protein: 1.38 × 1011-1.10 × 1012 particles), characterised by their size (â¼150 nm), expression of EV markers (CD63/81), and proposed endometrial cancer markers (L1CAM, ANXA2). Mass spectrometry-based proteomic profiling identified 2075 proteins present in at least one of the 18 samples. Compared to cell lysates, EVs were successfully depleted for mitochondrial and blood proteins and enriched for common EV markers and large secreted proteins. Further analysis highlighted significant differences in EV protein profiles between the high BMI subgroup and others, underlining the impact of comorbidities on the EV secretome. Interestingly, proteins differentially abundant in tissue subgroups were largely not also differential in matched EVs. This research identified secreted proteins known to be involved in endometrial cancer pathophysiology and proposed novel diagnostic biomarkers (EIF6, MUC16, PROM1, SLC26A2).
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Biomarcadores de Tumor , Neoplasias Endometriales , Vesículas Extracelulares , Obesidad , Proteoma , Humanos , Femenino , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Vesículas Extracelulares/metabolismo , Proteoma/metabolismo , Proteoma/análisis , Obesidad/metabolismo , Obesidad/patología , Biomarcadores de Tumor/metabolismo , Proteómica/métodos , Índice de Masa Corporal , Persona de Mediana EdadRESUMEN
Although older age is thought to confer immunosenescence, we found that older adults with inflammatory bowel disease are independently at higher risk to develop antibodies to infliximab. Additionally, older adults are less likely to receive escalated doses of infliximab.
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BACKGROUND: Patients with IBD may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. The question of the impact of biologic use on postoperative complications is a topic of active investigation. OBJECTIVE: A systematic literature review was performed to describe the current state of knowledge of the impact of perioperative biologic and tofacitinib use on postoperative complications in patients with IBD. DATA SOURCES: PubMed and Cochrane databases were searched. STUDY SELECTION: Studies between January 2000 and January 2023, in any language, were searched, followed by a snowball search identifying further studies in accordance with Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Articles regarding pediatric or endoscopic management were excluded. INTERVENTIONS: Preoperative or perioperative exposure to biologics in IBD was included. MAIN OUTCOME MEASURES: Infectious and noninfectious complications, including anastomotic leaks, surgical site infections, urinary tract infections, pneumonia, sepsis, septic shock, postoperative length of stay, readmission, and reoperation, were the main outcomes measured. RESULTS: A total of 28 studies were included for analysis in this review, including 7 meta-analyses or systematic reviews and 5 randomized studies. Snowball search identified 11 additional studies providing topical information. Overall, tumor necrosis factor inhibitors likely do not increase the risk of postoperative adverse outcomes, while data on other biologics and small-molecule agents are emerging. LIMITATIONS: This is a qualitative review including all study types. The varied nature of study types precludes quantitative comparison. CONCLUSIONS: Although steroids increase postoperative infectious and noninfectious complications, tumor necrosis factor inhibitors do not appear to increase postoperative infectious and noninfectious complications. There is a need for further perioperative data for other agents. See video from symposium .
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Productos Biológicos , Enfermedades Inflamatorias del Intestino , Complicaciones Posoperatorias , Humanos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Productos Biológicos/uso terapéutico , Productos Biológicos/efectos adversos , Enfermedades Inflamatorias del Intestino/cirugía , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/complicaciones , Colectomía/efectos adversos , Piperidinas/uso terapéutico , Piperidinas/efectos adversos , Pirimidinas/uso terapéutico , Pirimidinas/efectos adversos , Infección de la Herida Quirúrgica/epidemiología , Infección de la Herida Quirúrgica/prevención & control , Infección de la Herida Quirúrgica/etiología , Fuga Anastomótica/epidemiología , Fuga Anastomótica/etiología , Tiempo de Internación/estadística & datos numéricos , Inhibidores del Factor de Necrosis Tumoral/uso terapéutico , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Reoperación/estadística & datos numéricosRESUMEN
BACKGROUND: Patients with Crohn's disease (CD) are at risk of developing complications such as perianal fistulas. Patients with Crohn's perianal fistulas (CPF) are affected by fecal incontinence (FI), bleeding, pain, swelling, and purulent perianal discharge, and generally face a higher treatment burden than patients with CD without CPF. AIM: To gain insights into the burden of illness/quality of life in patients with CPF and their treatment preferences and satisfaction. METHODS: This cross-sectional observational study was conducted in patients with CD aged 21-90 years via a web-enabled questionnaire in seven countries (April-August 2021). Patients were recruited into three cohorts: Cohort 1 included patients without perianal fistulas; cohort 2 included patients with perianal fistulas without fistula-related surgery; and cohort 3 included patients with perianal fistulas and fistula-related surgery. Validated patient-reported outcome measures were used to assess quality of life. Drivers of treatment preferences were measured using a discrete choice experiment (DCE). RESULTS: In total, 929 patients were recruited (cohort 1, n = 620; cohort 2, n = 174; cohort 3, n = 135). Short Inflammatory Bowel Disease Questionnaire scores were worse for patients with CPF (cohorts 2 and 3) than for those with CD without CPF (cohort 1): Mean score 3.8 and 3.7 vs 4.1, respectively, (P < 0.001). Similarly, mean Revised FI and FI Quality of Life scores were worse for patients with CPF than for those with CD without CPF. Quality of Life with Anal Fistula scores were similar in patients with CPF with or without CPF-related surgery (cohorts 2 and 3): Mean score 41 and 42, respectively. In the DCE, postoperative discomfort and fistula healing rate were the most important treatment attributes influencing treatment choice: Mean relative importance 35.7 and 24.7, respectively. CONCLUSION: The burden of illness in CD is significantly higher for patients with CPF and patients rate lower postoperative discomfort and higher healing rates as the most desirable treatment attributes.
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Human-shark conflict has been managed through catch-and-kill policies in most parts of the world. More recently, there has been a greater demand for shark bite mitigation measures to improve protection for water users whilst minimizing harm to non-target and target species, particularly White Sharks (Carcharodon carcharias), given their status as a Threatened, Endangered, or Protected (TEP) species. A new non-lethal shark bite mitigation method, known as the Shark-Management-Alert-in-Real-Time (SMART) drumline, alerts responders when an animal takes the bait and thereby provides an opportunity for rapid response to the catch and potentially to relocate, tag, and release sharks. Thirty-six White Sharks were caught on SMART drumlines in New South Wales, Australia, and tagged with dorsal fin-mounted satellite-linked radio transmitters (SLRTs) and acoustic tags before release. Thirty-one sharks were located within 10 days, 22 of which provided high-quality locations (classes 1 to 3) suitable for analysis. Twenty-seven percent and 59% of these sharks were first detected within 10 and 50 h of release, respectively. For the first three days post-release, sharks moved and mostly remained offshore (>3.5 km from the coast), irrespective of shark sex and length. Thereafter, tagged sharks progressively moved inshore; however, 77% remained more than 1.9 km off the coast and an average of 5 km away from the tagging location, 10 days post-release. Sharks were acoustically detected for an average of 591 days post-release (ranging from 45 to 1075 days). Although five of the 36 sharks were not detected on acoustic receivers, SLRT detections for these five sharks ranged between 43 and 639 days post-release, indicating zero mortality associated with capture. These results highlight the suitability of SMART drumlines as a potential non-lethal shark bite mitigation tool for TEP species such as White Sharks, as they initially move away from the capture site, and thereby this bather protection tool diminishes the immediate risk of shark interactions at that site.
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Inflammatory bowel disease (IBD), consisting of Crohn's disease and ulcerative colitis, is recognized across the world, though Canada has among the highest burdens of IBD in the world. The Canadian Gastro-Intestinal Epidemiology Consortium (CanGIEC) led a six-province study that demonstrated the compounding prevalence of IBD in Canada from 400 per 100,000 in 2002 to 636 per 100,000 in 2014. The prevalence in 2023 is estimated at 825 per 100,000, meaning that over 320,000 people in Canada are living with IBD. Prevalence is forecasted to rise by 2.44% per year such that 1.1% of the population, 470,000 Canadians, will live with IBD by 2035. The overall incidence of IBD in 2023 is 30 per 100,000 person-years, indicating that over 11,000 Canadians will be newly diagnosed with IBD in 2023. Incidence is forecasted to rise by 0.58% per year up to 32.1 per 100,000 by 2035. The rising incidence of IBD is propelled by pediatric-onset IBD, which is rising by 1.23% per year from 15.6 per 100,000 in 2023 to 18.0 per 100,000 in 2035. In contrast, incidence rates among adults and seniors are relatively stable. Understanding the determinates of IBD has expanded through prospective cohort studies such as the Crohn's and Colitis Canada Genetic, Environmental, Microbial (CCC-GEM) project. Consensus recommendations towards diet, lifestyle, behavioural and environmental modifications have been proposed by international organizations with the goal of optimizing disease control and ultimately preventing the development of IBD. Despite these efforts, Canadian healthcare systems will need to prepare for the rising number of people living with IBD.
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Healthcare utilization among people living with inflammatory bowel disease (IBD) in Canada has shifted from inpatient management to outpatient management; fewer people with IBD are admitted to hospitals or undergo surgery, but outpatient visits have become more frequent. Although the frequency of emergency department (ED) visits among adults and seniors with IBD decreased, the frequency of ED visits among children with IBD increased. Additionally, there is variation in the utilization of IBD health services within and between provinces and across ethnocultural and sociodemographic groups. For example, First Nations individuals with IBD are more likely to be hospitalized than the general IBD population. South Asian children with Crohn's disease are hospitalized more often than their Caucasian peers at diagnosis, but not during follow-up. Immigrants to Canada who develop IBD have higher health services utilization, but a lower risk of surgery compared to individuals born in Canada. The total direct healthcare costs of IBD, including the cost of hospitalizations, ED visits, outpatient visits, endoscopy, cross-sectional imaging, and medications are rising rapidly. The direct health system and medication costs of IBD in Canada are estimated to be $3.33 billion in 2023, potentially ranging from $2.19 billion to $4.47 billion. This is an increase from an estimated $1.28 billion in 2018, likely due to sharp increases in the use of biologic therapy over the past two decades. In 2017, 50% of total direct healthcare costs can be attributed to biologic therapies; the proportion of total direct healthcare costs attributed to biologic therapies today is likely even greater.
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The COVID-19 pandemic had a monumental impact on the inflammatory bowel disease (IBD) community. At the beginning of the pandemic, knowledge on the effect of SARS-CoV-2 on IBD was lacking, especially in those with medication-suppressed immune systems. Throughout the pandemic, scientific literature exponentially expanded, resulting in clinical guidance and vaccine recommendations for individuals with IBD. Crohn's and Colitis Canada established the COVID-19 and IBD Taskforce to process and communicate rapidly transforming knowledge into guidance for individuals with IBD and their caregivers, healthcare providers, and policy makers. Recommendations at the onset of the pandemic were based on conjecture from experience of prior viruses, with a precautionary principle in mind. We now know that the risk of acquiring COVID-19 in those with IBD is the same as the general population. As with healthy populations, advanced age and comorbidities increase the risk for severe COVID-19. Individuals with IBD who are actively flaring and/or who require high doses of prednisone are susceptible to severe COVID-19 outcomes. Consequently, sustaining maintenance therapies (e.g., biologics) is recommended. A three-dose mRNA COVID-19 vaccine regimen in those with IBD produces a robust antibody response with a similar adverse event profile as the general population. Breakthrough infections following vaccine have been observed, particularly as the virus continues to evolve, which supports receiving a bivalent vaccine booster. Limited data exist on the impact of IBD and its therapies on long-term outcomes following COVID-19. Ongoing research is necessary to address new concerns manifesting in those with IBD throughout the evolving pandemic.
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People living with inflammatory bowel disease (IBD) and their caregivers are faced with indirect and out-of-pocket costs that they would not otherwise experience. These costs impact one's ability to contribute to the economy to their fullest potential. The indirect costs of IBD in Canada are estimated to be at least $1.51 billion in 2023 and include costs associated with lost productivity resulting from a combination of missed work (absenteeism), decreased workplace productivity (presenteeism), unemployment, premature mortality, and caregiving costs. Unemployment is the largest contributor to indirect costs ($1.14 billion), followed by costs of absenteeism and presenteeism ($285 million). Caregiving costs for children with IBD are estimated to be nearly $58 million. Canadians with IBD also pay $536 million every year for care that is not covered by universal or supplemental private health insurance; this includes allied healthcare (e.g., care provided by psychologists), medication, and other supportive therapy. Combined, the indirect and out-of-pocket costs of IBD in Canada are estimated at more than $2 billion CAD in 2023. This is substantially higher than the estimate of $1.29 billion in Crohn's and Colitis Canada's 2018 Impact of IBD report with differences attributable to a combination of rising prevalence, inflation, and the addition of presenteeism and caregiving costs to the total indirect costs.
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Sex (the physical and physiologic effects resulting from having specific combinations of sex chromosomes) and gender (sex-associated behaviours, expectations, identities, and roles) significantly affect the course of inflammatory bowel disease (IBD) and the experience of living with IBD. Sex-influenced physiologic states, like puberty, the menstrual cycle, pregnancy, and andropause/menopause may also impact and be impacted by IBD. While neither Crohn's disease nor ulcerative colitis is commonly considered sex-determined illnesses, the relative incidence of Crohn's disease and ulcerative colitis between males and females varies over the life cycle. In terms of gender, women tend to use healthcare resources at slightly higher rates than men and are more likely to have fragmented care. Women are more commonly prescribed opioid medications and are less likely than men to undergo colectomy. Women tend to report lower quality of life and have higher indirect costs due to higher rates of disability. Women are also more likely to take on caregiver roles for children with IBD. Women with IBD are more commonly burdened with adverse mental health concerns and having poor mental health has a more profound impact on women than men. Pregnant people with active IBD have higher rates of adverse outcomes in pregnancy, made worse in regions with poor access to IBD specialist care. The majority of individuals with IBD in Canada do not have access to a pregnancy-in-IBD specialist; access to this type of care has been shown to allay fears and increase knowledge among pregnant people with IBD.
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The burden of inflammatory bowel disease (IBD) (i.e., associated direct and indirect costs, prevalence of disease, personal impact to the individual and to caregivers) continues to increase in Canada. The prevalence of IBD has increased since Crohn's and Colitis Canada's 2018 Impact of IBD report from an estimated 270,000 Canadians living with IBD in 2018 to an estimated 322,600 Canadians living with IBD today in 2023. Consequently, associated costs of IBD have also dramatically increased from an estimated $2.57 billion in 2018 to an estimated $5.38 billion in 2023; this increase is due to multiple factors including increased prevalence of disease, inflation, and additional identified factors (e.g., presenteeism, costs of childcare). Beyond the economic impact of IBD, these diseases have a significant impact on people living with the disease and their caregivers, including different presentations of disease, different commonly associated extra-intestinal manifestations or comorbid conditions, and different barriers to accessing care. In this supplementary issue, we review: Evolving trends in the epidemiology of IBD; updated estimates of indirect and direct costs (including out-of-pocket costs) associated with IBD; information specific to IBD in children, adolescents, and seniors; issues related to IBD pertaining to sex and gender; information specific to risks associated with COVID-19 and cancer related to IBD; an overview of current treatments for IBD; and evolving care models, including access to care.
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Rising compounding prevalence of inflammatory bowel disease (IBD) (Kaplan GG, Windsor JW. The four epidemiological stages in the global evolution of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2021;18:56-66.) and pandemic-exacerbated health system resource limitations have resulted in significant variability in access to high-quality, evidence-based, person-centered specialty care for Canadians living with IBD. Individuals with IBD have identified long wait times, gaps in biopsychosocial care, treatment and travel expenses, and geographic and provider variation in IBD specialty care and knowledge as some of the key barriers to access. Care delivered within integrated models of care (IMC) has shown promise related to impact on disease-related outcomes and quality of life. However, access to these models is limited within the Canadian healthcare systems and much remains to be learned about the most appropriate IMC team composition and roles. Although eHealth technologies have been leveraged to overcome some access challenges since COVID-19, more research is needed to understand how best to integrate eHealth modalities (i.e., video or telephone visits) into routine IBD care. Many individuals with IBD are satisfied with these eHealth modalities. However, not all disease assessment and monitoring can be achieved through virtual modalities. The need for access to person-centered, objective disease monitoring strategies, inclusive of point of care intestinal ultrasound, is more pressing than ever given pandemic-exacerbated restrictions in access to endoscopy and cross-sectional imaging. Supporting learning healthcare systems for IBD and research relating to the strategic use of innovative and integrative implementation strategies for evidence-based IBD care interventions are greatly needed. Data derived from this research will be essential to appropriately allocating scarce resources aimed at improving person-centred access to cost-effective IBD care.