Lung imaging patterns in connective tissue disease-associated interstitial lung disease impact prognosis and immunosuppression response.

OBJECTIVES: Interstitial lung disease (ILD) in connective tissue diseases (CTD) have highly variable morphology. We aimed to identify imaging features and their impact on ILD progression, mortality and immunosuppression response. METHODS: Patients with CTD-ILD had high-resolution chest computed tomography (HRCT) reviewed by expert radiologists blinded to clinical data for overall imaging pattern (usual interstitial pneumonia [UIP]; non-specific interstitial pneumonia [NSIP]; organizing pneumonia [OP]; fibrotic hypersensitivity pneumonitis [fHP]; and other). Transplant-free survival and change in percent-predicted forced vital capacity (FVC) were compared using Cox and linear mixed effects models adjusted for age, sex, smoking, and baseline FVC. FVC decline after immunosuppression was compared with pre-treatment. RESULTS: Of 645 CTD-ILD patients, the frequent CTDs were systemic sclerosis (n = 215), rheumatoid arthritis (n = 127), and inflammatory myopathies (n = 100). NSIP was the most common pattern (54%), followed by UIP (20%), fHP (9%), and OP (5%). Compared with UIP, FVC decline was slower for NSIP (1.1%/year, 95%CI 0.2, 1.9) and OP (3.5%/year, 95%CI 2.0, 4.9), and mortality was lower for NSIP (HR 0.65, 95%CI 0.45, 0.93) and OP (HR 0.18, 95%CI 0.05, 0.57), but higher in fHP (HR 1.58, 95%CI 1.01, 2.40). The extent of fibrosis also predicted FVC decline and mortality. After immunosuppression, FVC decline was slower compared with pre-treatment in NSIP (by 2.1%/year, 95%CI 1.4, 2.8), with no change for UIP or fHP. CONCLUSION: Multiple radiologic patterns are possible in CTD-ILD, including a fHP pattern. NSIP and OP were associated with better outcomes and response to immunosuppression, while fHP had worse survival compared with UIP.

Asia-Pacific guidelines for managing functional dyspepsia overlapping with other gastrointestinal symptoms.

Contemporary systems for the diagnosis and management gastrointestinal symptoms not attributable to organic diseases (Functional GI Disorders, FGID, now renamed Disorders of Gut-Brain Interaction, DGBI) seek to categorize patients into narrowly defined symptom-based sub-classes to enable targeted treatment of patient cohorts with similar underlying putative pathophysiology. However, an overlap of symptom categories frequently occurs and has a negative impact on treatment outcomes. There is a lack of guidance on their management. An Asian Pacific Association of Gastroenterology (APAGE) working group was set up to develop clinical practice guidelines for management of patients with functional dyspepsia (FD) who have an overlap with another functional gastrointestinal disorder: FD with gastroesophageal reflux (FD-GERD), epigastric pain syndrome with irritable bowel syndrome (EPS-IBS), postprandial distress syndrome with IBS (PDS-IBS), and FD-Constipation. We identified putative pathophysiology to provide a basis for treatment recommendations. A management algorithm is presented to guide primary and secondary care clinicians.

Evidence-Based and Emerging Dietary Approaches to Upper Disorders of Gut-Brain Interaction.

Food ingestion is a major symptom trigger in functional esophageal and gastroduodenal disorders and gastroparesis. This review summarizes current knowledge and identifies areas of research on the role of food factors and the opportunities for dietary intervention in these disorders. While many patients experiencing functional esophageal and gastroduodenal disorders identify specific food items as symptom triggers, available data do not allow the identification of specific nutrient groups that are more likely to induce symptoms. In functional dyspepsia (FD), recent studies have shown the potential efficacy of a diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols, although the underlying mechanism of action is unclear. Reports of favorable responses to gluten elimination in patients with FD are confounded by the concomitant benefit of reduced intake of fructans, fermentable oligosaccharides, disaccharides, monosaccharides, and polyols present in wheat. Emerging data based on a 6-food elimination diet and confocal laser endomicroscopic evaluation of mucosal responses to food proteins suggest a role for duodenal allergic reactions in FD symptom generation. In patients with gastroparesis, a low-residue diet has been shown to improve symptoms. Novel dietary approaches under evaluation are the Mediterranean diet and the heating/cooling diet approach.

Pyrexia in a young infant - is height of fever associated with serious bacterial infection?

BACKGROUND: Febrile infants ≤ 90 days old make up a significant proportion of patients seeking care in the emergency department (ED). These infants are vulnerable to serious bacterial infections (SBIs) and early identification is required to initiate timely investigations and interventions. We aimed to study if height of an infant's temperature on presentation to the ED is associated with SBI. METHODS: We performed a retrospective chart review on febrile infants ≤ 90 days old presenting to our ED between 31st March 2015 and 28th February 2016. We compared triage temperature of febrile infants with and without SBIs. We presented sensitivity, specificity, positive and negative predictive values (PPV and NPV) of fever thresholds at triage. A multivariable regression was performed to study the association between height of temperature and the presence of SBI, and presented the adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI). RESULTS: Among 1057 febrile infants analysed, 207 (19.6%) had a SBI. Mean temperature of infants with a SBI was significantly higher than those without (mean 38.5 °C, standard deviation, SD 0.6 vs. 38.3 °C, SD 0.5, p < 0.005). For temperature ≥ 39 °C, sensitivity, specificity, PPV and NPV for SBI was 15.5% (95%CI 10.8-21.1%), 90.4% (95%CI 88.2-92.3%), 28.1% (95%CI 21.1-36.3%) and 81.4% (95%CI 80.5-82.4%) respectively. The height of fever was consistently associated with SBI after adjusting for age, gender and SIS (aOR 1.76, 95% CI 1.32-2.33, p < 0.001). However, 32 (15.5%) infants with SBIs had an initial triage temperature ≤ 38 °C. CONCLUSIONS: A higher temperature at triage was associated with a higher risk of SBI among febrile infants ≤ 90 days old. However, height of temperature must be used in conjunction with other risk factors to identify SBIs in young infants.

"It ain't over till it's over!" Risk-mitigation strategies for patients with gastrointestinal diseases in the aftermath of the COVID-19 pandemic.

The available COVID-19 literature has focused on specific disease manifestations, infection control, and delivery or prioritization of services for specific patient groups in the setting of the acute COVID-19 pandemic. Local health systems aim to contain the COVID-19 pandemic and hospitals and health-care providers rush to provide the capacity for a surge of COVID-19 patients. However, the short, medium-term, and long-term outcomes of patients with gastrointestinal (GI) diseases without COVID-19 will be affected by the ability to develop locally adapted strategies to meet their service needs in the COVID-19 setting. To mitigate risks for patients with GI diseases, it is useful to differentiate three phases: (i) the acute phase, (ii) the adaptation phase, and (iii) the consolidation phase. During the acute phase, service delivery for patients with GI disease will be curtailed to meet competing health-care needs of COVID-19 patients. During the adaptation phase, GI services are calibrated towards a "new normal," and the consolidation phase is characterized by rapid introduction and ongoing refinement of services. Proactive planning with engagement of relevant stakeholders including consumer representatives is required to be prepared for a variety of scenarios that are dictated by thus far undefined long-term economic and societal impacts of the pandemic. Because substantial changes to the delivery of services are likely to occur, it is important that these changes are embedded into quality and research frameworks to ensure that data are generated that support evidence-based decision-making during the adaptation and consolidation phases.

Food Therapy in Sinosphere Asia.

Traditional Chinese Food Therapy has long been an integral part of dietary practices in Sinosphere Asia. This therapy is defined by the classification of foods into cooling (Yin) and heaty (Yang) and the manipulation of dietary intake of these foods as a therapeutic strategy for chronic diseases. Both functional dyspepsia (FD) and irritable bowel syndrome (IBS) are chronic, functional gut disorders widely prevalent in Sinosphere Asia. Diet is increasingly recognized as a symptom trigger in FD and IBS, and the evidence suggesting the utility of diet therapies as front-line management is growing, particularly in the West. Specifically, a diet low in Fermentable, Oligosaccharides, Disaccharides, Monosaccharides, and Polyols is an efficacious therapy for patients with IBS. In contrast, a proportion of patients with IBS in Sinosphere Asia utilize Chinese Food Therapy for symptom management. Chinese Food Therapy provides an attractive target for integration with evidence-based Western dietary therapies as a management strategy in FD and IBS. However, significant gaps in research exist with the utility of Chinese Food Therapy that first need to be addressed. This includes a lack of standardization for heaty and cooling classification, limited mechanistic rationale or clinical studies supporting its efficacy in FD and IBS, and the lack of an ideal practitioner for implementation of Chinese Food Therapy. Hence, the review provides a summary of the role of diet and nutrition in Sinosphere Asia with an emphasis on FD and IBS, and an examination of how modern dietary practices may be able to be integrated into practices in this region.

Breath Hydrogen Testing in East and Southeast Asia.

Breath hydrogen tests are popular, noninvasive tests for the assessment of carbohydrate fermentation in patients with irritable bowel syndrome (IBS) and functional dyspepsia (FD). There is limited information regarding the utility of breath hydrogen and methane tests in IBS and FD patients in East and Southeast Asia. This review aims to summarize current literature about common indications of breath testing in this region, the genesis of functional gastrointestinal symptoms by provocative breath testing and provide suggestions for correct use. The most common testing indication is the assessment of lactose intolerance, followed by small intestinal bacterial overgrowth (SIBO) and differentiation of intestinal gas profiles in research setting. Studies in this region not only documented a high prevalence of lactose malabsorption but a population, both healthy and IBS, that is highly symptomatic to typical lactose intakes. Breath hydrogen assessment of other fermentable carbohydrates (FODMAPs) are fairly uncommon, whereas methane breath testing is almost nonexistent. Cumulative hydrogen production following lactulose was also not excessive in IBS patients compared with controls. The evidence however, for the detection of SIBO suggests limited reliability in the use of lactulose or glucose breath testing alone and inconclusive data on its correlation with symptoms. Conversely, little has been carried out in FD. In conclusion, breath testing should be limited in the predicting patients with SIBO for directing clinical management but can be considered in the objective assessment of lactose malabsorption within a low FODMAP diet. Recommendations to improve the interpretation of breath testing in research were also provided.

Dietary Interventions in Liver Cirrhosis.

Liver cirrhosis is associated with significant nutritional risks that often result in serious hepatic complications and poor survival rates. Diet is an important but underutilized aspect in the treatment modality of cirrhosis. Therefore, the aims of this review are to ascertain nutritional risks associated with its pathophysiology and to summarize existing evidence that support dietary recommendations for managing this patient population. Alterations in substrate utilization for energy production is a main feature of liver cirrhosis, resulting in increased catabolism of protein stores and a predisposition toward protein-energy malnutrition, even in the early stages of the disease. The body of evidence suggests that a high energy and protein (>1.2 g/kg body weight/d) diet consumed frequently and late in the evening is effective in improving nutritional status of these patients and has been associated with improved hospitalization and mortality rates. The use of branched-chain amino acid supplementation shows promise in reducing cirrhosis-related complications but are currently limited by adverse gastrointestinal symptoms and poor palatability. Furthermore exploration of dietary manipulation of branched-chain amino acid warrants further examination. Evidence is also accumulating that protein intake should not be restricted in patients with hepatic encephalopathy with earlier studies of protein restriction neglecting to account for the relative increase in fermentable fiber which would reduce the absorption of ammonia into the portal system in a way similar to supplementation with lactulose. Finally, a major finding of this review is the need to improve the quality and quantity of dietary intervention studies for patients with liver cirrhosis, particularly with the use of partial or whole dietary sources. In conclusion, dietary management of cirrhosis is not a one-size fits all approach but should be implemented earlier on in the treatment algorithm to improve the clinical prognosis of cirrhosis.

The low-FODMAP diet in the management of functional dyspepsia in East and Southeast Asia.

Functional dyspepsia (FD) is a common disorder in East and Southeast Asia where subjects experience post prandial fullness/bloating, early satiety, belching, epigastric pain, and/or burning. A subset of patients with FD experience triggers exclusively related to meals, defined as the post prandial distress syndrome in the Rome IV guidelines. There is significant overlap of symptoms and implicated pathogenic factors with another common functional gastrointestinal disorder, irritable bowel syndrome (IBS) and in fact, a significant proportion of subjects have FD/IBS overlap. The introduction of the low-FODMAP diet has changed the paradigm of treatment for IBS. Like IBS, dietary management appears to be important to patients with FD and clinicians treating the condition. This review aims to examine the current role of diet in the management of FD in East and Southeast Asia, with an exploration of the likely efficacy and mechanisms of action of the low-FODMAP diet in this region.

Imaging trends in suspected appendicitis-a Canadian perspective.

PURPOSE: The purpose of our study was to assess trends in the imaging of suspected appendicitis in adult patients in emergency departments of academic centers in Canada. METHODS: A questionnaire was sent to all 17 academic centers in Canada to be completed by a radiologist who works in emergency radiology. The questionnaires were sent and collected over a period of 4 months from October 2015 to February 2016. RESULTS: Sixteen centers (94%) responded to the questionnaire. Eleven respondents (73%) use IV contrast-enhanced computed tomography (CT) as the imaging modality of choice for all patients with suspected appendicitis. Thirteen respondents (81%) use ultrasound as the first modality of choice in imaging pregnant patients with suspected appendicitis. Eleven respondents (69%) use ultrasound (US) as the first modality of choice in patients younger than 40 years of age. Ten respondents (67%) use ultrasound as the first imaging modality in female patients younger than 40 years of age. When CT is used, 81% use non-focused CT of the abdomen and pelvis, and 44% of centers use oral contrast. Thirteen centers (81%) have ultrasound available 24 h a day/7 days a week. At 12 centers (75%), ultrasound is performed by ultrasound technologists. Four centers (40%) perform magnetic resonance imaging (MRI) in suspected appendicitis in adult patients at the discretion of the attending radiologist. Eleven centers (69%) have MRI available 24/7. All 16 centers (100%) use unenhanced MRI. CONCLUSIONS: Various imaging modalities are available for the work-up of suspected appendicitis. Although there are North American societal guidelines and recommendations regarding the appropriateness of the multiple imaging modalities, significant heterogeneity in the first-line modalities exist, which vary depending on the patient demographics and resource availability. Imaging trends in the use of the first-line modalities should be considered in order to plan for the availability of the imaging examinations and to consider plans for an imaging algorithm to permit standardization across multiple centers. While this study examined the imaging trends specifically in Canada, there are implications to other countries seeking to streamline imaging protocols and determining appropriateness of the first-line imaging modalities.

KCNK9 imprinting syndrome-further delineation of a possible treatable disorder.

Patients with KCNK9 imprinting syndrome demonstrate congenital hypotonia, variable cleft palate, normal MRIs and EEGs, delayed development, and feeding problems. Associated facial dysmorphic features include dolichocephaly with bitemporal narrowing, short philtrum, tented upper lip, palatal abnormalities, and small mandible. This disorder maps to chromosomal region 8q24, and it is caused by a specific missense mutation 770G>A in exon 2, replacing glycine at position 236 by arginine (G236R) in the maternal copy of KCNK9 within this locus. KCNK9 (also called TASK3) encodes a member of the two pore- domain potassium channel (K2P) subfamily. This gene is normally imprinted with paternal silencing, thus a mutation in the maternal copy of the gene will result in disease, whereas a mutation in the paternal copy will have no effect. Exome sequencing in four new patients with developmental delay and central hypotonia revealed de novo G236R mutations. Older members of a previously reported Arab-Israeli family have intellectual disability of variable severity, persistent feeding difficulties in infancy with dysphagia of liquids and dysphonia with a muffled voice in early adulthood, generalized hypotonia, weakness of proximal muscles, elongated face with narrow bitemporal diameter, and reduced facial movements. We describe the clinical features in four recently recognized younger patients and compare them with those found in members of the originally reported Arab-Israeli family and suggest this may be a treatable disorder. © 2016 Wiley Periodicals, Inc.

Gastroesophageal Reflux Disease: Cross-Sectional Study Demonstrating Rising Prevalence in a Chinese Population.

BACKGROUND AND AIMS: The prevalence of gastroesophageal reflux disease (GERD) is consistently lower in the Chinese than in white populations. Population-based data tracking the time trend of GERD prevalence in Chinese subjects is conflicting. This study examines the population prevalence, risk factors, and time trend associated with GERD in a Chinese population. METHODS: A population-based cross-sectional study utilizing a validated GERD questionnaire administered by a telephone survey was performed on 3360 Chinese subjects from Hong Kong. GERD prevalence rates in 2011 were compared with prevalence rates in 2002 and 2006. Multiple logistic regressions were performed to determine the risk factors associated with weekly GERD. RESULTS: A total of 2074 subjects (mean age, 48.1±18.2 y; range 18 to 94; 63.1% female) completed the survey (response rate 61.7%). The prevalence of GERD as defined by the Montreal definition was 3.8%. The prevalence of weekly GERD had increased by 1.3% between 2002 and 2011, which represents an at least 50% relative increase (P<0.0005). A diagnosis of weekly GERD was associated with noncardiac chest pain [odds ratio (OR), 1.7; 95% confidence interval (CI), 1.034-2.9; P=0.037], dyspepsia (OR, 5.1; 95% CI, 3.0-8.8; P<0.005), and an acid feeling in the stomach (OR, 3.0; 95% CI, 1.8-5.1). CONCLUSIONS: GERD rates in the ethnic Chinese have risen over the last decade. Despite this, variables associated with a survey diagnosis of GERD remain ostensibly unchanged. GERD research in East Asia should focus on the factors driving the rapid rise in prevalence rates and the association with more atypical symptoms of GERD.

Chronology of the Radiographic Appearances of the Calcium Sulfate-Calcium Phosphate Synthetic Bone Graft Composite Following Resection of Bone Tumors: A Follow-up Study of Postoperative Appearances.

PURPOSE: The objective of the study was to characterize the radiographic appearance of graft resorption and new bone incorporation into a postresection defect of the calcium-sulfate calcium-phosphate synthetic bone graft composite following resection of benign bone tumours. METHODS: Twenty-five patients who underwent treatment with the CaSO4/CaPO4 synthetic graft following bone tumour resection were retrospectively identified from our oncology database. Postoperative radiographs were assessed for: 1) combined partial graft resorption and ingrowth at the graft site; 2) complete graft resorption with complete incorporation of new bone into the defect. After chronologically grouping radiographs, the volume of graft material used to fill bony defects, radiographic evidence of complications, and patterns of resorption were recorded. RESULTS: Partial resorption of graft material/partial ingrowth of new bone was seen in 21 patients at 2.5 months postoperatively. Complete resorption of graft with complete new bone incorporation at the graft site was seen in 94% of cases (15 of 16) by 10 months after surgery. Mean time to complete incorporation of new bone was 6.7 months. Time to resorption of the graft with new bone ingrowth was found to be related to the volume of graft used with smaller volumes showing earlier resorption. For all cases demonstrating resorption (21 of 21), the pattern observed was peripheral to central. Five patients developed complications, including tumour recurrence, cyst formation, and graft site infection. CONCLUSION: Our study suggests a characteristic time and volume related radiographic pattern of resorption and new bone ingrowth with the CaSO4/CaPO4 synthetic graft. Findings that deviate from this pattern may represent complication and warrant additional follow-up.

CaRE@ELLICSR: Effects of a clinically integrated, group-based, multidimensional cancer rehabilitation program.

BACKGROUND: Although oncology clinical practice guidelines recognize the need and benefits of exercise, the implementation of these services into cancer care delivery remains limited. We developed and evaluated the impact of a clinically integrated 8-week exercise and education program (CaRE@ELLICSR). METHODS: We conducted a mixed methods, prospective cohort study to examine the effects of the program. Each week, participants attended a 1-h exercise class, followed by a 1.5-h education session. Questionnaires, 6-min walk tests (6MWT), and grip strength were completed at baseline (T0), 8 weeks (T1), and 20 weeks (T2). Semi-structured interviews were conducted with a sub-sample of participants about their experience with the program. RESULTS: Between September 2017 and February 2020, 277 patients enrolled in the program and 210 consented to participate in the research study. The mean age of participants was 55 years. Participants were mostly female (78%), white/Caucasian (55%) and half had breast cancer (50%). Participants experienced statistical and clinically meaninful improvements from T0 to T1 in disability, 6MWT, grip strength, physical activity, and several cancer-related symptoms. These outcomes were maintained 3 months after program completion (T2). Qualitative interviews supported these findings and three themes emerged from the interviews: (1) empowerment and control, (2) supervision and internal program support, and (3) external program support. CONCLUSIONS: This study demonstrates the impact of overcoming common organizational barriers to deliver exercise and rehabilitation as part of routine care. CaRE@ELLICSR demonstrated clinically meaningful improvements in patient-reported and functional outcomes and was considered beneficial and important by participants for their recovery and wellbeing.

A portable optical pulsatile flowmetry demonstrates strong clinical relevance for diabetic foot perfusion assessment.

We present a robust, cost-effective (<2000 USD), and portable optical diffuse speckle pulsatile flowmetry (DSPF) device with a flexible handheld probe for deep tissue blood flow measurement in the human foot as well as a first-in-man observational clinical study using the proposed optical device for tissue ischemia assessment and peripheral artery disease (PAD) diagnosis. Blood flow in tissue is inherently pulsatile in nature. However, most conventional methods cannot measure deep tissue-level pulsatile blood flow noninvasively. The proposed optical device can measure tissue-level pulsatile blood flow ∼6 mm underneath the skin surface. A new quantitative tissue perfusion index (TPIDSPF) based on frequency domain analysis of the pulsatile blood flow waveform is defined to assess tissue ischemia status. Through a clinical study involving 66 subjects, including healthy individuals and diabetes patients with and without PAD, TPIDSPF demonstrated strong correlations of 0.720 with transcutaneous tissue partial oxygen pressure (TcPO2) and 0.652 with toe-brachial index (TBI). Moreover, among the three methods, TPIDSPF demonstrated the highest area under the curve for PAD diagnosis among diabetes patients, with a notable value of 0.941. The promising clinical results suggest that the proposed optical method has the potential to be an effective clinical tool for identifying PAD among the diabetic cohort.

A two-phased study on the use of remote photoplethysmography (rPPG) in paediatric care.

Background: Advancements in medical technologies have led to the development of contact-free methods of haemodynamic monitoring such as remote photoplethysmography (rPPG). rPPG uses video cameras to interpret variations in skin colour related to blood flow, which are analysed to generate vital signs readings. rPPG potentially ameliorates problems like fretfulness and fragile skin contact associated with conventional probes in children. While rPPG has been validated in adults, no prior validation has been performed in children. Methods: A two-phased prospective cross-sectional single-centre study was conducted from January to April 2023 to evaluate the feasibility, acceptability, and accuracy of obtaining heart rate (HR), respiratory rate (RR) and oxygen saturation (SpO2) using rPPG in children, compared to the current standard of care. In Phase 1, we recruited patients ≤16 years from the neonatal and paediatric wards. We excluded preterm neonates with gestational age <35 weeks and newborns <24 hours old. The rPPG webcam was positioned 30 cm from the face. After 1 minute of facial scanning, readings generated were compared with pulse oximetry for HR and SpO2, and manual counting for RR. Correlation and Bland-Altman analyses were performed. In Phase 2, we focused on the population in whom there was potential correlation between rPPG and the actual vital signs. Results: Ten neonates and 28 children aged 5 to 16 years were recruited for Phase 1 (765 datapoints). All patients were haemodynamically stable and normothermic. Patients and caregivers showed high acceptability to rPPG. rPPG values were clinically discrepant for children <10 years. For those ≥10 years, moderate correlation was observed for HR, with Spearman's correlation coefficient (Rs) of 0.50 [95% confidence intervals (CI): 0.42, 0.57]. We performed Phase 2 on 23 patients aged 12 to 16 years (559 datapoints). Strong correlation was observed for HR with Rs=0.82 (95% CI: 0.78, 0.85). There was weak correlation for SpO2 and RR (Rs=-0.25 and -0.02, respectively). Conclusions: Our study showed that rPPG is acceptable and feasible for neonates and children aged 5 to 16 years, and HR values in older children aged 12 to 16 years correlated well with the current standard. The rPPG algorithms need to be further refined for younger children, and for obtaining RR and SpO2 in all children. If successful, rPPG will provide a viable contact-free alternative for assessing paediatric vital signs, with potential use in remote monitoring and telemedicine.

Venous and arterial disease in inflammatory bowel disease.

Awareness is increasing that risk of venous thromboembolism and development of atherosclerosis is elevated in patients with some chronic inflammatory diseases. This review aimed to examine the risk of vascular disease in patients with inflammatory bowel disease (IBD) and to identify potential pathogenic mechanisms and therapeutic approaches. An extensive literature search was conducted using MEDLINE database, Cochrane Library and international conference abstracts for studies pertaining to venous and arterial thromboembolism in adult IBD patients. There is a 1.1-3.6 fold risk of venothromboembolism in IBD, affecting 0.55-6.15% of patients. Risks are increased during a flare or with chronically active inflammation. Evidence is building that there may be a modestly increased risk of arterial disease overall, despite evidence that traditional risk factors may be reduced. Multiple pathogenic factors have been identified including endothelial dysfunction, inflammation-mediated calcium deposition in the media of arteries, hyperhomocysteinemia, platelet activation, and altered coagulation and fibrinolysis. The key to active and preventive therapy is to effectively treat inflammation. Recommendations for prophylaxis of venothromboembolism have followed guidelines where they exist and have been extrapolated from studies of other at-risk conditions, as have those for arterial disease, where screening for risk factors and actively treating abnormalities is encouraged. In conclusion, patients with IBD are at considerably increased risk of venothromboembolism and probably of arterial disease, in particular mesenteric ischemia and ischemic heart disease. Increased penetration of gaps between this knowledge and clinical therapeutic action to prevent thromboembolic events into IBD clinical practice is needed.

Integration and Application of Radiologic Patterns From Clinical Practice Guidelines on Idiopathic Pulmonary Fibrosis and Fibrotic Hypersensitivity Pneumonitis.

BACKGROUND: Clinical practice guidelines separately describe radiologic patterns of usual interstitial pneumonia (UIP) and fibrotic hypersensitivity pneumonitis (fHP), without direction on whether or how to apply these approaches concurrently within a single patient. RESEARCH QUESTION: How can we integrate guideline-defined radiologic patterns to diagnose interstitial lung disease (ILD) and what are the pitfalls associated with described patterns that require reassessment in future guidelines? STUDY DESIGN AND METHODS: Patients from the Canadian Registry for Pulmonary Fibrosis underwent detailed reevaluation in standardized multidisciplinary discussion. CT scan features were quantified by chest radiologists masked to clinical data, and guideline-defined patterns were assigned. Clinical data then were provided to the radiologist and an ILD clinician, who jointly determined the leading diagnosis. RESULTS: Clinical-radiologic diagnosis in 1,593 patients was idiopathic pulmonary fibrosis (IPF) in 26%, fHP in 12%, connective tissue disease-associated ILD (CTD-ILD) in 34%, idiopathic pneumonia with autoimmune features in 12%, and unclassifiable ILD in 10%. Typical and probable UIP patterns corresponded to a diagnosis of IPF in 66% and 57% of patients, respectively. Typical fHP pattern corresponded to an fHP clinical diagnosis in 65% of patients, whereas compatible fHP was nonspecific and associated with CTD-ILD or IPAF in 48% of patients. No pattern ruled out CTD-ILD. Gas trapping affecting > 5% of lung parenchyma on expiratory imaging was an important feature broadly separating compatible and typical fHP from other patterns (sensitivity, 0.77; specificity, 0.91). INTERPRETATION: An integrated approach to guideline-defined UIP and fHP patterns is feasible and supports > 5% gas trapping as an important branch point. Typical or probable UIP and typical fHP patterns have moderate predictive values for a corresponding diagnosis of IPF and fHP, although occasionally confounded by CTD-ILD; compatible fHP is nonspecific.

XIAP-associated factor 1 (XAF1), a novel target of p53, enhances p53-mediated apoptosis via post-translational modification.

The role of X chromosome-linked inhibitor of apoptosis protein (XIAP)-associated factor 1 (XAF1) in mediating apoptosis has been reported but the underlying mechanism remains unclear. The present study was designed to examine the putative interaction between XAF1 and p53 and the functional importance of this interaction in regulation of apoptosis in human gastric and colon cancer cells. We first identified XAF1 as a novel target gene of p53 by the chromatin immunoprecipitation (CHIP) assay and demonstrated that wild-type p53, but not mutant p53, down-regulated XAF1 at both mRNA and protein levels, which acted mostly under the condition of high expression of XAF1 and was associated with the physical interaction between p53 and the XAF1 promoter. We also found that the over-expression of XAF1 led to activation of wild-type p53 via post-translational modification in cells with or without DNA damage, which resulting in p53 nuclear accumulation and its increased transcriptional activity and enhancing p53-dependent apoptosis. These findings suggest that a potential novel feedback loop exists between XAF1 and wild-type p53.