Bone cement repair of malleus handle fractures: Intraoperative video and case report of two patients.

Isolated malleus fractures are a rare occurrence with few reported cases in the literature. Symptoms include sudden otalgia, hearing loss, tinnitus and aural fullness. Work-up and diagnosis are based on a combination of thorough anamnesis and careful otoscopic evaluation or high-resolution computer tomography. We present two cases of isolated malleus handle fractures who were diagnosed based on a combination of pneumatic otoscopy and tympanometry. Both fractures were surgically repaired using hydroxyapatite bone cement as showcased in the supplemental video material. Post-operative audiometry showed improvement in the pure-tone-average of both patients as well as normalisation of tympanometry. Isolated malleus fracture should be suspected in cases of sudden hearing loss and tinnitus following digital manipulation of the outer ear canal together with a conductive hearing loss with a mostly high-frequent air-bone-gap and hypercompliant tympanometry with hypermobility of the tympanic membrane on pneumatic insufflation. Surgical repair of the fracture using bone cement has good hearing outcomes and leads to improvement in auditory symptoms.

Imaging and haemodynamic parameters associated with clinical outcomes following isolated tricuspid valve surgery.

INTRODUCTION: Isolated tricuspid valve surgery (TVS) may be associated with high morbidity and mortality. The aim of this study was to investigate the association of preoperative imaging and haemodynamic data derived from echocardiography (ECHO), cardiac magnetic resonance (CMR) and right heart catheterisation (RHC) with postoperative outcomes following TVS. METHODS: In a retrospective cohort study, patients who underwent isolated TVS at our institution between 2012 and 2020 were screened and followed up to 1 year. We only included those who had all three tests before surgery: ECHO, CMR and RHC. Patients with congenital heart disease, infective endocarditis and those who underwent concomitant valve or pericardial surgery were excluded. The primary outcome was a composite of mortality and congestive heart failure at 1 year. Time-to-event analyses at 1 year and Cox proportional hazards regression analyses were performed. RESULTS: A total of 60 patients were included (mean age of 60±14 years, 63% women), of whom 67% underwent TV repair. The primary outcome occurred in 16 patients (27%) with a 1-year mortality of 7%. It was associated with ECHO-derived right ventricular (RV) free wall strain and RHC-derived RV systolic and diastolic as well as mean pulmonary pressures. On multivariable Cox regression analysis, only RV systolic and diastolic pressures were significantly associated with the primary outcome at 1 year (HRs=5.9 and 3.4, respectively, p<0.05). CONCLUSION: Baseline invasive haemodynamic assessment could have a strong association with clinical outcomes and help risk-stratify patients undergoing isolated TVS.

Impact of an Endolymphatic Sac Tumor on Subjective and Objective Audiovestibular Function.

OBJECTIVE: This study reports subjective and objective audiovestibular function in patients diagnosed with an endolymphatic sac tumor (ELST), to evaluate the clinical implication of vestibular testing in ELST patients. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral center/university hospital. PATIENTS: Five patients diagnosed with unilateral ELST. INTERVENTION: Subjective and objective audiovestibular tests; pure-tone average; speech discrimination score; the Video Head Impulse Test; the cervical vestibular evoked myogenic potential test; the caloric irrigation test; the Speech, Spatial and Qualities of Hearing Scale; the Tinnitus Handicap Inventory; and the Dizziness Handicap Inventory. MAIN OUTCOME MEASURE: Findings and characteristics of both subjective and objective audiovestibular functions. RESULTS: The mean pure-tone average and the mean speech discrimination score were 49 dB HL and 68% on the tumor ear and 13 dB HL and 99% contralaterally. The mean Speech, Spatial and Qualities of Hearing Scale score was 84, and the mean Tinnitus Handicap Inventory score was 64. Caloric testing showed a mean unilateral weakness of 80%. The Video Head Impulse Test of the lateral semicircular canal revealed refixation saccades on all tumor ears and an average gain value of 0.75 on the tumor ear versus 0.94 contralaterally. No cervical vestibular evoked myogenic potentials were elicited on the tumor side, whereas all but one was elicited contralaterally. The average Dizziness Handicap Inventory score was 47. CONCLUSION: A characteristic pattern of abnormal caloric findings, refixation saccades, and normal vestibulo-ocular reflex gain alongside sensorineural hearing loss on the tumor ear was identified. Asymmetric sensorineural hearing loss in any patient should lead to objective vestibular evaluation to strengthen not only a targeted tumor surveillance strategy and the indication for imaging, but also the design of vestibular rehabilitation. In addition, vestibular findings may guide the choice of surgical approach.

Use of an Amplatzer ASD Occlusion Device for the Closure of an Ascending Aortic Pseudoaneurysm Presenting as Hemoptysis.

Aortic pseudoaneurysms can commonly be caused by previous thoracic surgery, trauma, and infection, quickly becoming life-threatening if ruptured. This pathology is typically asymptomatic and incidentally found on imaging; however, few cases have outlined hemoptysis as a presenting symptom for aortic pseudoaneurysms. Traditionally, management of these patients included surgical correction; however, percutaneous approaches have emerged as a safe alternative, helping to reduce the risk of morbidity and mortality associated with surgical correction. This report seeks to describe a case in which hemoptysis was the symptom unveiling the finding of a thoracic ascending aortic pseudoaneurysm and the use of an Amplatzer atrial septal defect (ASD) occlusion device as a viable option to safely resolve the disease process.

Comparison of oscillometric, non-invasive and invasive arterial pressure monitoring in patients undergoing laparoscopic bariatric surgery - a secondary analysis of a prospective observational study.

BACKGROUND: Oscillometric, non-invasive blood pressure measurement (NIBP) is the first choice of blood pressure monitoring in the majority of low and moderate risk surgeries. In patients with morbid obesity, however, it is subject to several limitations. The aim was to compare arterial pressure monitoring by NIBP and a non-invasive finger-cuff technology (Nexfin®) with the gold-standard invasive arterial pressure (IAP). METHODS: In this secondary analysis of a prospective observational, single centre cohort study, systolic (SAP), diastolic (DAP) and mean arterial pressure (MAP) were measured at 16 defined perioperative time points including posture changes, fluid bolus administration and pneumoperitoneum (PP) in patients undergoing laparoscopic bariatric surgery. Absolute arterial pressures by NIBP, Nexfin® and IAP were compared using correlation and Bland Altman analyses. Interchangeability was defined by a mean difference ≤ 5 mmHg (SD ≤8 mmHg). Percentage error (PE) was calculated as an additional statistical estimate. For hemodynamic trending, concordance rates were analysed according to the Critchley criterion. RESULTS: Sixty patients (mean body mass index of 49.2 kg/m2) were enrolled and data from 56 finally analysed. Pooled blood pressure values of all time points showed a significant positive correlation for both NIPB and Nexfin® versus IAP. Pooled PE for NIBP versus IAP was 37% (SAP), 35% (DAP) and 30% (MAP), for Nexfin versus IAP 23% (SAP), 26% (DAP) and 22% (MAP). Correlation of MAP was best and PE lowest before induction of anesthesia for NIBP versus IAP (r = 0.72; PE 24%) and after intraoperative fluid bolus administration for Nexfin® versus IAP (r = 0.88; PE: 17.2%). Concordance of MAP trending was 90% (SAP 85%, DAP 89%) for NIBP and 91% (SAP 90%, DAP 86%) for Nexfin®. MAP trending was best during intraoperative ATP positioning for NIBP (97%) and at induction of anesthesia for Nexfin® (97%). CONCLUSION: As compared with IAP, interchangeability of absolute pressure values could neither be shown for NIBP nor Nexfin®, however, NIBP showed poorer overall correlation and precision. Overall trending ability was generally high with Nexfin® surpassing NIBP. Nexfin® may likely render individualized decision-making in the management of different hemodynamic stresses during laparoscopic bariatric surgery, particularly where NIBP cannot be reliably established. TRIAL REGISTRATION: The non-interventional, observational study was registered retrospectively at ( NCT03184285 ) on June 12, 2017.

Intraepithelial and Lamina Propria Lymphocytes Do Not Correlate With Symptoms or Exposures in Microscopic Colitis.

INTRODUCTION: Microscopic colitis, a common cause of diarrhea, is characterized by a largely normal appearance of the mucosa but increased numbers of lymphocytes in the epithelium and lamina propria on microscopy. We sought to determine whether T-cell percentage was associated with exposures or symptoms. METHODS: We conducted a case-control study that enrolled patients referred for colonoscopy for diarrhea. Patients were classified as microscopic colitis cases or controls by an experienced pathologist. Participants provided information on symptoms and exposures during a telephone or internet survey. Research biopsies from the ascending colon and descending colon were examined using immunofluorescence stains for CD3, CD8, and FOXP3 to determine percent T cells per total epithelial or lamina propria cells. Digital images were analyzed by regions of interest using Tissue Studio. RESULTS: There were 97 microscopic colitis cases and 165 diarrhea controls. There was no association between demographic factors and percentage of intraepithelial or lamina propria T cells. In cases, the mean percent T cells were similar in the right colon and left colon. There was no association between mean percent T cells and stool frequency or consistency. There was no association with irritable bowel syndrome, abdominal pain, or medications purported to cause microscopic colitis. DISCUSSION: The lack of association between the density of T cells and medications raises further doubts about their role in disease etiology. Loose and frequent stools in patients with microscopic colitis are not correlated with T-cell density.

Bacteria-Cancer Interface: Awaiting the Perfect Storm.

Epidemiological evidence reveal a very close association of malignancies with chronic inflammation as a result of persistent bacterial infection. Recently, more studies have provided experimental evidence for an etiological role of bacterial factors disposing infected tissue towards carcinoma. When healthy cells accumulate genomic insults resulting in DNA damage, they may sustain proliferative signalling, resist apoptotic signals, evade growth suppressors, enable replicative immortality, and induce angiogenesis, thus boosting active invasion and metastasis. Moreover, these cells must be able to deregulate cellular energetics and have the ability to evade immune destruction. How bacterial infection leads to mutations and enriches a tumour-promoting inflammatory response or micro-environment is still not clear. In this review we showcase well-studied bacteria and their virulence factors that are tightly associated with carcinoma and the various mechanisms and pathways that could have carcinogenic properties.

Increased colonic expression of ACE2 associates with poor prognosis in Crohn's disease.

The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. We examined the expression of colonic ACE2 in 67 adult CD and 14 NIBD control patients using RNA-seq and quantitative (q) RT-PCR. We validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. Colonic ACE2 expression was significantly higher in a subset of adult CD patients which was defined as the ACE2-high CD subset. IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of CD diagnosis, and a Cox regression analysis found that high ACE2 levels is an independent risk factor for surgery (OR 2.17; 95% CI, 1.10-4.26; p = 0.025). Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that can impact CD disease-related outcomes.

[Auditory brainstem implantation].

In this review, we discuss the auditory brainstem implant (ABI), which is a neuroprosthetic device being an advanced hearing aid in cases of bilateral, profound or complete hearing impairment due to a non-functional or absent cochlear nerve, or an inner ear malformation precluding cochlear implantation. Originally indicated in patients with bilateral vestibular schwannomas caused by neurofibromatosis type 2, the ABI has in recent years seen an increase in the aural rehabilitation of congenitally deaf children. Outcomes for patients are mixed, but generally the device leads to a reasonable improvement in speech perception.

Increased Colonic Expression of ACE2 Associates with Poor Prognosis in Crohn's disease.

BACKGROUND AND AIMS: The host receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is highly expressed in small intestine. Our aim was to study colonic ACE2 expression in Crohn's disease (CD) and non-inflammatory bowel disease (non-IBD) controls. We hypothesized that the colonic expression levels of ACE2 impacts CD course. METHODS: We examined the expression of colon ACE2 using RNA-seq and quantitative (q) RT-PCR from 69 adult CD and 14 NIBD control patients. In a subset of this cohort we validated ACE2 protein expression and localization in formalin-fixed, paraffin-embedded matched colon and ileal tissues using immunohistochemistry. The impact of increased ACE2 expression in CD for the risk of surgery was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. To provide critical support for the generality of our findings, we analyzed previously published RNA-seq data from two large independent cohorts of CD patients. RESULTS: Colonic ACE2 expression was significantly higher in a subset of adult CD patients (ACE2-high CD). IHC in a sampling of ACE2-high CD patients confirmed high ACE2 protein expression in the colon and ileum compared to ACE2-low CD and NIBD patients. Notably, we found that ACE2-high CD patients are significantly more likely to undergo surgery within 5 years of diagnosis, with a Cox regression analysis finding that high ACE2 levels is an independent risk factor (OR 2.18; 95%CI, 1.05-4.55; p=0.037). CONCLUSION: Increased intestinal expression of ACE2 is associated with deteriorated clinical outcomes in CD patients. These data point to the need for molecular stratification that may impact CD disease-related outcomes.

Perioperative non-invasive versus semi-invasive cardiac index monitoring in patients with bariatric surgery - a prospective observational study.

BACKGROUND: In morbidly obese patients undergoing laparoscopic bariatric surgery, the combination of obesity-related comorbidities, pneumoperitoneum and extreme posture changes constitutes a high risk of perioperative hemodynamic complications. Thus, an advanced hemodynamic monitoring including continuous cardiac index (CI) assessment is desirable. While invasive catheterization may bear technical difficulties, transesophageal echocardiography is contraindicated due to the surgical procedure. Evidence on the clinical reliability of alternative semi- or non-invasive cardiac monitoring devices is limited. The aim was to compare the non-invasive vascular unloading to a semi-invasive pulse contour analysis reference technique for continuous CI measurements in bariatric surgical patients. METHODS: This prospective observational study included adult patients scheduled for elective, laparoscopic bariatric surgery after obtained institutional ethics approval and written informed consent. CI measurements were performed using the vascular unloading technique (Nexfin®) and semi-invasive reference method (FloTrac™). At 10 defined measurement time points, the influence of clinically indicated body posture changes, passive leg raising, fluid bolus administration and pneumoperitoneum was evaluated pre- and intraoperatively. Correlation, Bland-Altman and concordance analyses were performed. RESULTS: Sixty patients (mean BMI 49.2 kg/m2) were enrolled into the study and data from 54 patients could be entered in the final analysis. Baseline CI was 3.2 ± 0.9 and 3.3 ± 0.8 l/min/m2, respectively. Pooled absolute CI values showed a positive correlation (rs = 0.76, P < 0.001) and mean bias of of - 0.16 l/min/m2 (limits of agreement: - 1.48 to 1.15 l/min/m2) between the two methods. Pooled percentage error was 56.51%, missing the criteria of interchangeability (< 30%). Preoperatively, bias ranged from - 0.33 to 0.08 l/min/m2 with wide limits of agreement. Correlation of CI was best (rs = 0.82, P < 0.001) and percentage error lowest (46.34%) during anesthesia and after fluid bolus administration. Intraoperatively, bias ranged from - 0.34 to - 0.03 l/min/m2 with wide limits of agreement. CI measurements correlated best during pneumoperitoneum and after fluid bolus administration (rs = 0.77, P < 0.001; percentage error 35.95%). Trending ability for all 10 measurement points showed a concordance rate of 85.12%, not reaching the predefined Critchley criterion (> 92%). CONCLUSION: Non-invasive as compared to semi-invasive CI measurements did not reach criteria of interchangeability for monitoring absolute and trending values of CI in morbidly obese patients undergoing bariatric surgery. TRIAL REGISTRATION: The study was registered retrospectively on June 12, 2017 with the registration number NCT03184272 .

Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier Integrity in Patients With Crohn's Disease.

BACKGROUND & AIMS: Intestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn's disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets and functional consequences are unknown. METHODS: microRNA-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by quantitative polymerase chain reaction in colonic IECs. Functional characterization of activin receptor-like kinase 1 (ACVRL1 or ALK1) in IECs was performed ex vivo using 2-dimensional cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator. RESULTS: ALK1 was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3'-untranslated region reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in a 5-ethynyl-2-deoxyuridine proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling increased colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared with healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a transepithelial electrical resistance permeability assay. Lower colonic ALK1 expression was identified as an independent risk factor for surgery and was associated with a higher risk of endoscopic relapse in CD patients. CONCLUSIONS: Decreased colonic ALK1 disrupted colonic IEC barrier integrity and was associated with poor clinical outcomes in CD patients.

Chronic Antibiotic Dependent Pouchitis Is Associated With Older Age at the Time of Ileal Pouch Anal Anastomosis (J-pouch) Surgery.

BACKGROUND: Risk factors for the development of chronic antibiotic dependent pouchitis (CADP) are not well understood. METHODS: Using multivariable logistic regression, we compared clinical factors between 194 patients with acute antibiotic responsive pouchitis or CADP. RESULTS: Individuals with CADP were significantly older (40.9 vs 30.8 years, P < 0.001) and demonstrated a longer disease duration before IPAA (10.3 vs 7.0 years, P = 0.004). Age ≥55 years at the time of IPAA was significantly associated with CADP (adjusted odds ratio = 4.35, 95% confidence interval = 1.01-18.7). CONCLUSIONS: Although older age should not represent a barrier to IPAA, further studies evaluating etiologies of this association are warranted.

Enterococcus faecalis Gluconate Phosphotransferase System Accelerates Experimental Colitis and Bacterial Killing by Macrophages.

Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in this PTS and measured bacterial growth and PTS gene expression in minimal medium supplemented with selected carbohydrates. We show that E. faecalis upregulates OG1RF_12399 transcription specifically in the presence of gluconate and that E. faecalis strains lacking, or harboring a single point mutation in, OG1RF_12399-12402 are unable to grow in minimal medium containing gluconate. We colonized germfree wild-type and colitis-prone interleukin-10-deficient mice with defined bacterial consortia containing the E. faecalis strains and measured inflammation and bacterial abundance in the colon. We infected macrophage and intestinal epithelial cell lines with the E. faecalis strains and measured intracellular bacterial survival and proinflammatory cytokine secretion. The presence of OG1RF_12399-12402 is not required for E. faecalis colonization of the mouse intestine but is associated with an accelerated onset of experimental colitis in interleukin-10-deficient mice, altered bacterial composition in the colon, enhanced E. faecalis survival within macrophages, and increased proinflammatory cytokine secretion by colon tissue and macrophages. Further studies of bacterial carbohydrate metabolism in general, and E. faecalis PTS-gluconate in particular, during inflammation may identify new mechanisms of disease pathogenesis.

Understanding operator stent choice in the catheterization laboratory using a pre-procedure survey: Opportunities for quality improvement.

OBJECTIVES: We sought to characterize how the perceived risk of early dual antiplatelet therapy (DAPT) discontinuation is incorporated into operator decision-making regarding stent choice, using a simple pre-procedure survey screening for clinical variables that may lead to early DAPT discontinuation. BACKGROUND: Understanding which factors influence operator decision-making regarding stent choice during percutaneous coronary intervention (PCI) could help identify areas for quality improvement. METHODS: We retrospectively identified 1202 patients who underwent PCI from July 2008 to January 2013 at the Durham Veterans Affairs Medical Center. We excluded patients without a complete pre-procedure survey within 14days of PCI, repeat procedures on the same patient and those who received both drug-eluting stents (DES) and bare-metal stents (BMS) or no stent during PCI, leaving 864 patients. The primary outcome was the independent association of "yes" responses to survey items with the odds of DES use during PCI. RESULTS: Of 864 patients, 661 received DES and 203 received BMS. A "yes" response to "planned major surgery or dental work in the next year" (OR 0.20, 95% CI 0.11-0.36, p<0.001), "recent bleeding event or bleeding diathesis" (OR 0.31, 95% CI 0.14-0.68, p=0.003) or "currently taking Coumadin" (OR 0.39, 95% CI 0.19-0.78, p=0.007) was independently associated with lower odds of DES use. CONCLUSIONS: Responses to 3 items on a simple pre-procedure survey screening for clinical variables that may lead to early DAPT discontinuation were independently associated with stent type used during PCI, suggesting the importance of these factors in an operator's stent choice.

A Large Cardiac Papillary Fibroelastoma Arising from the Coumadin Ridge: Unusual Location and Presentation.

•The coumadin ridge is a very unusual location for a cardiac PFE.•Although benign, large, mobile cardiac PFEs can pose a significant embolic risk.•Multimodality CV imaging can differentiate cardiac PFE from other cardiac tumors.

Escherichia coli heme oxygenase modulates host innate immune responses.

Induction of mammalian heme oxygenase (HO)-1 and exposure of animals to carbon monoxide (CO) ameliorates experimental colitis. When enteric bacteria, including Escherichia coli, are exposed to low iron conditions, they express an HO-like enzyme, chuS, and metabolize heme into iron, biliverdin and CO. Given the abundance of enteric bacteria residing in the intestinal lumen, our postulate was that commensal intestinal bacteria may be a significant source of CO and those that express chuS and other Ho-like molecules suppress inflammatory immune responses through release of CO. According to real-time PCR, exposure of mice to CO results in changes in enteric bacterial composition and increases E. coli 16S and chuS DNA. Moreover, the severity of experimental colitis correlates positively with E. coli chuS expression in IL-10 deficient mice. To explore functional roles, E. coli were genetically modified to overexpress chuS or the chuS gene was deleted. Co-culture of chuS-overexpressing E. coli with bone marrow-derived macrophages resulted in less IL-12p40 and greater IL-10 secretion than in wild-type or chuS-deficient E. coli. Mice infected with chuS-overexpressing E. coli have more hepatic CO and less serum IL-12 p40 than mice infected with chuS-deficient E. coli. Thus, CO alters the composition of the commensal intestinal microbiota and expands populations of E. coli that harbor the chuS gene. These bacteria are capable of attenuating innate immune responses through expression of chuS. Bacterial HO-like molecules and bacteria-derived CO may represent novel targets for therapeutic intervention in inflammatory conditions.

Implementation of the ABL-90 blood gas analyzer in a ground-based mobile emergency care unit.

Point-of Care analysis is increasingly being applied in the prehospital scene. Arterial blood gas analysis is one of many new initiatives adding to the diagnostic tools of the prehospital physician. In this paper we present a study on the feasibility of the Radiometer ABL-90 in a ground-based Mobile Emergency Care Unit and report on some clinical situations in which the apparatus has proven beneficial.

MicroRNAs Classify Different Disease Behavior Phenotypes of Crohn's Disease and May Have Prognostic Utility.

BACKGROUND: There is a dire need for reliable prognostic markers that can guide effective therapeutic intervention in Crohn's disease (CD). We examined whether different phenotypes in CD can be classified based on colonic microRNA (miRNA) expression and whether miRNAs have prognostic utility for CD. METHODS: High-throughput sequencing of small and total RNA isolated from colon tissue from patients with CD and controls without Inflammatory Bowel Disease (non-IBD) was performed. To identify miRNAs associated with specific phenotypes of CD, patients were stratified according to disease behavior (nonstricturing, nonpenetrating; stricturing; penetrating), and miRNA profiles in each subset were compared with those of the non-IBD group. Validation assays were performed using quantitative reverse transcription polymerase chain reaction. These miRNAs were further evaluated by quantitative reverse transcriptase polymerase chain reaction on formalin-fixed, paraffin-embedded tissue (index biopsies) of patients with nonpenetrating CD at the time of diagnosis that either retained the nonpenetrating phenotype or progressed to penetrating/fistulizing CD. RESULTS: We found a suite of miRNAs, including miR-31-5p, miR-215, miR-223-3p, miR-196b-5p, and miR-203 that stratify patients with CD according to disease behavior independent of the effect of inflammation. Furthermore, we also demonstrated that expression levels of miR-215 in index biopsies of patients with CD might predict the likelihood of progression to penetrating/fistulizing CD. Finally, using a novel statistical simulation approach applied to colonic RNA-sequencing data for patients with CD and non-IBD controls, we identified miR-31-5p and miR-203 as candidate master regulators of gene expression profiles associated with CD. CONCLUSIONS: miRNAs may serve as clinically useful prognostic markers guiding initial therapy and identifying patients who would benefit most from effective intervention.

Small heat-shock proteins, IbpAB, protect non-pathogenic Escherichia coli from killing by macrophage-derived reactive oxygen species.

Many intracellular bacterial pathogens possess virulence factors that prevent detection and killing by macrophages. However, similar virulence factors in non-pathogenic bacteria are less well-characterized and may contribute to the pathogenesis of chronic inflammatory conditions such as Crohn's disease. We hypothesize that the small heat shock proteins IbpAB, which have previously been shown to reduce oxidative damage to proteins in vitro and be upregulated in luminal non-pathogenic Escherichia strain NC101 during experimental colitis in vivo, protect commensal E. coli from killing by macrophage-derived reactive oxygen species (ROS). Using real-time PCR, we measured ibpAB expression in commensal E. coli NC101 within wild-type (wt) and ROS-deficient (gp91phox(-/-)) macrophages and in NC101 treated with the ROS generator paraquat. We also quantified survival of NC101 and isogenic mutants in wt and gp91phox(-/-) macrophages using gentamicin protection assays. Similar assays were performed using a pathogenic E. coli strain O157:H7. We show that non-pathogenic E. coli NC101inside macrophages upregulate ibpAB within 2 hrs of phagocytosis in a ROS-dependent manner and that ibpAB protect E. coli from killing by macrophage-derived ROS. Moreover, we demonstrate that ROS-induced ibpAB expression is mediated by the small E. coli regulatory RNA, oxyS. IbpAB are not upregulated in pathogenic E. coli O157:H7 and do not affect its survival within macrophages. Together, these findings indicate that ibpAB may be novel virulence factors for certain non-pathogenic E. coli strains.