Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

Autologous fat graft injections for the treatment of perianal fistulas in Crohn's disease: a systematic review and single-arm meta-analysis.

BACKGROUND: Crohn's perianal fistulas are often refractory to standard management. Fat graft injections are hypothesised to improve fistula healing rates. We evaluated the treatment efficacy of fat graft injections for Crohn's perianal fistulas in a systematic review (PRISMA). METHODS: We completed database searches of MEDLINE (Ovid), Embase, and PubMed. All studies published in English in full text or abstract, from January 2001 to August 2021, evaluating fat graft injections for Crohn's perianal fistulas were selected. Included randomized controlled trials, single-arm intervention trials, cohort studies, and case series; excluded single case reports. Primary outcome was pooled clinical healing, defined as non-draining treated fistulas, or closure, defined as closure of treated fistulas. Secondary outcomes were clinical healing, clinical closure, radiologic response, and adverse events. RESULTS: Of 1258 publications identified, 891 articles were assessed for eligibility, and 107 relevant for manuscript review. Forty-nine patients received fat graft injections for Crohn's perianal fistulas across four single-arm intervention trials. Clinical healing or closure was achieved in 74% in a pooled single-arm meta-analysis (95% confidence interval: 57%, 85%), with moderate heterogeneity between studies. Clinical healing was achieved in 20% and 60% at 3 and 12 months, respectively. Clinical closure was achieved in 83% at 6 months. Variable parameters were used to define radiologic response, with success rates from 20% to 67%. Minimal adverse events were reported. CONCLUSION: Fat graft injections show promise as a novel treatment for Crohn's perianal fistulas in this systematic review and meta-analysis. Assessment in controlled matched studies is warranted.

Higher Anti-tumor Necrosis Factor-α Levels Correlate With Improved Radiologic Outcomes in Crohn's Perianal Fistulas.

BACKGROUND & AIMS: Higher anti-tumor necrosis factor-α (TNF) drug levels are associated with improved clinical healing of Crohn's perianal fistulas. It is unclear whether this leads to improved healing on radiologic assessment. We aimed to evaluate the association between anti-TNF drug levels and radiologic outcomes in perianal fistulising Crohn's disease. METHODS: A cross-sectional retrospective multicenter study was undertaken. Patients with perianal fistulising Crohn's disease on maintenance infliximab or adalimumab, with drug levels within 6 months of perianal magnetic resonance imaging were included. Patients receiving dose changes or fistula surgery between drug level and imaging were excluded. Radiologic disease activity was scored using the Van Assche Index, with an inflammatory subscore calculated using indices: T2-weighted imaging hyperintensity, collections >3 mm diameter, rectal wall involvement. Primary endpoint was radiologic healing (inflammatory subscore ≤6). Secondary endpoint was radiologic remission (inflammatory subscore = 0). RESULTS: Of 193 patients (infliximab, n = 117; adalimumab, n = 76), patients with radiologic healing had higher median drug levels compared with those with active disease (infliximab 6.0 vs 3.9 µg/mL; adalimumab 9.1 vs 6.2 µg/mL; both P < .05). Patients with radiologic remission also had higher median drug levels compared with those with active disease (infliximab 7.4 vs 3.9 µg/mL; P < .05; adalimumab 9.8 vs 6.2 µg/mL; P = .07). There was a significant incremental reduction in median inflammatory subscores with higher anti-TNF drug level tertiles. CONCLUSIONS: Higher anti-TNF drug levels were associated with improved radiologic outcomes on magnetic resonance imaging in perianal fistulising Crohn's disease, with an incremental improvement at higher drug level tertiles for both infliximab and adalimumab.

Long-term outcomes of perianal fistulizing Crohn's disease in the biologic era.

BACKGROUND AND AIM: While the advent of biologic therapy has led to improved outcomes in perianal fistulizing Crohn's disease (pfCD), loss of response is common. Previous studies suggest that patients who achieve radiological healing (with healing of underlying tracts on magnetic resonance imaging [MRI]) have a longer duration of response. The aim of this study was to characterize MRI outcomes of pfCD at a specialist inflammatory bowel disease (IBD) unit and compare the long-term clinical outcomes between patients achieving MRI and clinical healing. METHODS: A retrospective analysis of perianal fistulizing Crohn's patients treated at one specialist IBD unit was performed. Records were reviewed for patient demographics, disease history, clinical assessments, investigation results, and disease flares. Clinical remission was defined as closure of all baseline fistula openings. Radiological healing was defined as the absence of any T2-hyperintense sinuses, tracts, or collections. The primary end-point was rate of MRI healing. The secondary outcome was defined as flare-free period (time between clinical or radiological healing and patients' first signs/symptoms requiring therapy escalation). RESULTS: A total of 93 patients were included, with a median follow-up of 4.8 years (interquartile range, 2.4-6 years). Of 44 patients, 22 (50%) achieved clinical remission, while 15 of 93 (16%) achieved radiological healing. Of 22 patients, 10 (45%) with clinical remission had a subsequent disease flare (median time of 7 months) compared with 3 of 15 (20%) patients with MRI healing (median time of 3.6 years). Radiological healing was associated with a significantly longer flare-free period (P = 0.01). CONCLUSION: Radiological healing occurs less commonly but represents a deeper form of healing, associated with improved long-term clinical outcomes.

Immunosuppression as a risk factor for COVID-19: a meta-analysis.

BACKGROUND: While immunosuppression poses a theoretical increase in the risk of COVID-19, the nature of this relationship is yet to be ascertained. AIMS: To determine whether immunosuppressed patients are at higher risk of COVID-19 to help inform the management of patients receiving immunosuppressant therapies during the pandemic. METHODS: We performed a random-effects meta-analysis of data from studies that reported on the prevalence of immunosuppression among patient cohorts with COVID-19. RESULTS: Sixty full-text publications were identified. In total, six individual studies were included in the final analysis, contributing a total of 10 049 patients with COVID-19 disease. The prevalence of immunosuppressed patients among the study cohorts with COVID-19 ranged from 0.126% to 1.357%. In the pooled cohort a total of 64/10 049 (0.637%) patients with COVID-19 disease was immunosuppressed. Observed to expected ratios were used to compare the prevalence of immunosuppression in cohorts with confirmed COVID-19 disease to the background prevalence of immunosuppression in the general community. The observed to expected ratio of immunosuppression among patients with COVID-19 illness, relative to the general community, was 0.12 (95% confidence interval: 0.05-0.27). CONCLUSIONS: Compared to the general population, immunosuppressed patients were not at significantly increased risk of COVID-19 infection. This finding provides support for current expert consensus statements, which have recommended the continuation of immunosuppressant therapy in the absence of COVID-19.

Assessing aCCess to Investigations in Inflammatory Bowel Disease (ACCID): results from an international survey.

BACKGROUND: Multiple investigations are available to aid the diagnosis and monitoring of disease activity in inflammatory bowel disease (IBD). Fecal calprotectin (FC) is an established surrogate for intestinal inflammatory activity. Therapeutic drug monitoring (TDM) including thiopurine metabolites, anti-tumor necrosis factor (TNF) levels and antidrug antibody measurements are a step toward personalized medicine in IBD, but face access barriers. We aimed to assess test availability and barriers for these investigations in European practice. METHODS: Five-hundred questionnaires were distributed to workshop participants at the 11th Congress of the European Crohn's and Colitis Organisation (ECCO). Access to FC, TDM for thiopurines and anti-tumor necrosis factor agents, as well as factors associated with usage and barriers to access were recorded. RESULTS: Responses were obtained from 195 attendees from 38 countries across a range of practices, healthcare settings and levels of experience. FC was available to 92.3% while access to anti-TNF (78.9%, P = 0.02 vs. thiopurine TDM, P = 0.0002 vs. FC) and thiopurine TDM (67.7%, P = 0.0001) were less widespread. Cost was a frequently cited barrier to test access or usage, with access having a significant West-East and North-South divide across all three investigations. The strongest independent predictor of access to all tests was healthcare spending per capita (P = 0.005 for FC; P < 0.0001 for both TDM). CONCLUSION: FC, anti-TNF and thiopurine TDM are increasingly incorporated as part of routine practice in IBD care across Europe and have the potential to impact positively on patient care. However, access barriers remain of which we found test cost the most significant with the investment required to reduce these barriers.

Non-invasive fibrosis algorithms are clinically useful for excluding cirrhosis in prisoners living with hepatitis C.

BACKGROUND AND AIMS: Prison-based HCV treatment rates remain low due to multiple barriers, including accessing transient elastography for cirrhosis determination. The AST-to-platelet ratio index (APRI) and FIB-4 scores have excellent negative predictive value (NPV) in hospital cohorts to exclude cirrhosis. We investigated their performance in a large cohort of prisoners with HCV infection. METHODS: This was a retrospective cohort study of participants assessed by a prison-based hepatitis program. The sensitivity, specificity, NPV and positive predictive value (PPV) of APRI and FIB-4 for cirrhosis were then analysed, with transient elastography as the reference standard. The utility of age thresholds as a trigger for transient elastography was also explored. RESULTS: Data from 1007 prisoners were included. The median age was 41, 89% were male, and 12% had cirrhosis. An APRI cut-off of 1.0 and FIB-4 cut-off of 1.45 had NPVs for cirrhosis of 96.1% and 96.6%, respectively, and if used to triage prisoners for transient elastography, could reduce the need for this investigation by 71%. The PPVs of APRI and FIB-4 for cirrhosis at these cut-offs were low. Age ≤35 years alone had a NPV for cirrhosis of 96.5%. In those >35 years, the APRI cut-off of 1.0 alone had a high NPV >95%. CONCLUSION: APRI and FIB-4 scores can reliably exclude cirrhosis in prisoners and reduce requirement for transient elastography. This finding will simplify the cascade of care for prisoners living with hepatitis C.

Radiological outcomes in perianal fistulizing Crohn's disease: A systematic review and meta-analysis.

Perianal fistulas are a common and debilitating manifestation of Crohn's disease. Since the advent of biological agents, patient outcomes appear to have improved. While rates of clinical response and remission are well characterized in literature, magnetic resonance imaging (MRI) outcomes remain less so. This is despite previous studies demonstrating the persistence of fistula tracts on MRI, in spite of clinical healing, suggesting radiological markers of improvement may be more accurate. The aims of this study were to systematically review the literature for all studies reporting on MRI outcomes following biological therapy and to compare rates of radiological healing to clinical remission. A search was performed according to the Preferred Reporting Items For Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Nine articles were included, with a total sample size of 259 patients. Of these 259 patients, 47% achieved clinical remission following induction therapy and 42% following a median of 52 weeks' maintenance therapy. Out of the 259 patients, 7% achieved radiological healing in the short term and 25% in the long term. The odds ratio of MRI versus clinical healing was 0.10 (95% confidence interval [CI], 0.02-0.39) and 0.43 (95% CI, 0.26-0.71), respectively, at those corresponding time points. MRI healing of perianal fistulizing Crohn's, while arguably a more accurate assessment of treatment response, is significantly less common than clinical remission. Heterogeneity exists in the definition of radiological and clinical response, leading to variation in reported rates. Further studies, directly comparing the long-term outcomes of patients achieving clinical remission and MRI healing are required, to better inform the role of MRI follow up in clinical practice.

Interactions Between Indigenous Women Awaiting Childbirth Away From Home and Their Southern, Non-Indigenous Health Care Providers.

We examine patient-provider interactions for Indigenous childbirth evacuees. Our analysis draws on in-depth interviews with 25 Inuit and First Nations women with medically high-risk pregnancies who were transferred or medevacked from northern Quebec to receive maternity care at a tertiary hospital in a southern city in the province. We supplemented the patient data with interviews from eight health care providers. Three themes related to patient-provider interactions are discussed: evacuation-related stress, hospital bureaucracy, and stereotypes. Findings show that the quality of the patient-provider interaction is contingent on individual health care providers' ability to connect with Indigenous patients and overcome cultural and institutional barriers to communication and trust-building. The findings point to the need for further training of medical professionals in the delivery of culturally safe care and addressing bureaucratic constraints in the health care system to improve patient-provider communication and overall relationship quality.

Nutritional supplements and their effect on glucose control.

As diabetes mellitus (DM) continues to be a growing health concern, many people have been turning to natural health products (NHPs) in order to manage this condition, adjunctive to, or even in place of conventional therapies. In order to keep up with this trend, research focussing on the efficacy and mechanisms behind the most common NHPs has been growing amongst the scientific community. The purpose of this chapter is to search and compile scientific literature focussing on the most commonly used NHPs in diabetes treatment, so to educate health professionals on the efficacy, safety and dosage of these products. From our findings, it is apparent that there are promising results from many studies on the potential benefit of NHPs in the treatment of diabetes. Nonetheless, many of the herbs and single nutraceuticals still require further studies in order to confirm safety, dosage and potential interactions with standard conventional therapies. Soluble fibre, alpha lipoic acid, milk thistle, prickly pear cactus and pycnogenol appear to be the most beneficial in the treatment of diabetes.

Nutritional supplements and their effect on glucose control.

Type 2 diabetes is a growing health concern. The use of nutritional supplements by patients with type 2 diabetes is estimated at somewhere between 8% to 49%. The objective of this review was to search the scientific literature for advances in the treatment and prevention of type 2 diabetes with nutritional supplements. Twelve databases were searched with a focus on extracting studies published in the past 3 years. The following nutritional supplements were identified as potentially beneficial for type 2 diabetes treatment or prevention: vitamins C and E, α-lipoic acid, melatonin, red mold, emodin from Aloe vera and Rheum officinale, astragalus, and cassia cinnamon. Beta-carotene was shown to be ineffective in the prevention of type 2 diabetes. Ranging from preclinical to clinical, there is evidence that nutritional supplements may be beneficial in the treatment or prevention of type 2 diabetes. Health providers should investigate drug-nutritional supplement interactions prior to treatment.

A comparative review of thermography as a breast cancer screening technique.

Breast cancer is the most frequently diagnosed cancer of women in North America. Despite advances in treatment that have reduced mortality, breast cancer remains the second leading cause of cancer induced death. Several well established tools are used to screen for breast cancer including clinical breast exams, mammograms, and ultrasound. Thermography was first introduced as a screening tool in 1956 and was initially well accepted. However, after a 1977 study found thermography to lag behind other screening tools, the medical community lost interest in this diagnostic approach. This review discusses each screening tool with a focus brought to thermography. No single tool provides excellent predictability; however, a combination that incorporates thermography may boost both sensitivity and specificity. In light of technological advances and maturation of the thermographic industry, additional research is required to confirm the potential of this technology to provide an effective non-invasive, low risk adjunctive tool for the early detection of breast cancer.

Imitation of hierarchical action structure by young children.

To provide the first systematic test of whether young children will spontaneously perceive and imitate hierarchical structure in complex actions, a task was devised in which a set of 16 elements can be modelled through either of two different, hierarchically organized strategies. Three-year-old children showed a strong and significant tendency to copy whichever of the two hierarchical approaches they witnessed an adult perform. Responses to an element absent in demonstrations, but present at test, showed that children did not merely copy the chain of events they had witnessed, but acquired hierarchically structured rules to which the new element was assimilated. Consistent with this finding, children did not copy specific sequences of actions at lower hierarchical levels.