The TGF-β1/p53/PAI-1 Signaling Axis in Vascular Senescence: Role of Caveolin-1.

Stress-induced premature cellular senescence is a significant factor in the onset of age-dependent disease in the cardiovascular system. Plasminogen activator inhibitor-1 (PAI-1), a major TGF-β1/p53 target gene and negative regulator of the plasmin-based pericellular proteolytic cascade, is elevated in arterial plaques, vessel fibrosis, arteriosclerosis, and thrombosis, correlating with increased tissue TGF-β1 levels. Additionally, PAI-1 is necessary and sufficient for the induction of p53-dependent replicative senescence.

Imaging Features Associated With Failure of Nonoperative Management of Intraabdominal Abscesses in Crohn Disease.

Background: Intraabdominal abscess management decisions in the treatment of Crohn disease (CD) can be challenging. Our aim was to determine the effect of clinical, medication use, and imaging disease characteristics on the need for future surgical management.

Methods: A retrospective chart review was performed in patients with CD hospitalized for abscess confirmed by imaging between 2008 and 2016.

TGF-β1-p53 cooperativity regulates a profibrotic genomic program in the kidney: molecular mechanisms and clinical implications.

Chronic kidney disease affects >15% of the U.S. population and >850 million individuals worldwide.

Challenges in the Pathophysiology, Diagnosis, and Management of Intestinal Fibrosis in Inflammatory Bowel Disease.

Intestinal fibrosis is a common complication of inflammatory bowel disease (IBD) that is usually the consequence of chronic inflammation. Although the currently available anti-inflammatory therapies have had little impact on intestinal fibrosis in Crohn’s disease (CD), increased understanding of the pathophysiology and the development of therapies targeting fibrogenic pathways hold promise for the future. One of the critical challenges is how reduction or reversal of intestinal fibrosis should be defined and measured in the setting of clinical trials and drug approval.

Controlling intestinal colonization of high-risk haematology patients with ESBL-producing Enterobacteriaceae: a randomized, placebo-controlled, multicentre, Phase II trial (CLEAR).

Objectives: We assessed the efficacy and safety of an oral antimicrobial regimen for short- and long-term intestinal eradication of ESBL-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EC/KP) in immunocompromised patients.

Methods: We performed a randomized (2:1), double-blind multicentre Phase II study in four haematology-oncology departments. Patients colonized with ESBL-EC/KP received a 7 day antimicrobial regimen of oral colistin (2 × 106 IU 4×/day), gentamicin (80 mg 4×/day) and fosfomycin (three administrations of 3 g every 72 h), or placebo.

The adequacy of lymph node clearance in colon cancer surgery performed in a non-specialist centre; implications for practice.

Background: Despite recent medical advances, surgery remains the mainstay treatment in colon cancer. It is well established that better patient outcomes are achieved when complex surgery including pancreatic, oesophageal and rectal surgeries are carried out in high-volume centres. However, it is unclear as to whether or not colon cancer patients receive the same benefit.

Generation and selection of antibodies for a novel immunochromatographic lateral flow test to rapidly identify OXA-23-like-mediated carbapenem resistance in Acinetobacter baumannii.

Introduction: The spread of carbapenem-resistant Acinetobacter baumannii has led to a worldwide healthcare problem. Carbapenem resistance in A. baumannii is mainly mediated by the acquisition of the carbapenem-hydrolyzing oxacillinase OXA-23.

Characterizing intestinal strictures of Crohn's disease by endoscopic photoacoustic imaging.

Crohn's disease (CD) is one type of inflammatory bowel disease where both inflammation and fibrosis cause the thickening of the bowel wall and development of the strictures. Accurate assessment of the strictures is critical for the management of CD because the fibrotic strictures must be removed surgically. In this study, a prototype capsule-shaped acoustic resolution photoacoustic (PA) endoscope, which can perform mulitwavelength side-view scanning, was developed to characterize the intestinal strictures of CD.

Performance of a Deep Learning Model vs Human Reviewers in Grading Endoscopic Disease Severity of Patients With Ulcerative Colitis.

Importance: Assessing endoscopic disease severity in ulcerative colitis (UC) is a key element in determining therapeutic response, but its use in clinical practice is limited by the requirement for experienced human reviewers.

Objective: To determine whether deep learning models can grade the endoscopic severity of UC as well as experienced human reviewers.

Design, Setting, And Participants: In this diagnostic study, retrospective grading of endoscopic images using the 4-level Mayo subscore was performed by 2 independent reviewers with score discrepancies adjudicated by a third reviewer.

Rac-GTPase promotes fibrotic TGF-β1 signaling and chronic kidney disease EGFR, p53, and Hippo/YAP/TAZ pathways.

Rac-GTPases are major regulators of cytoskeletal remodeling and their deregulation contributes to numerous pathologies. Whether or how Rac promotes tubulointerstitial fibrosis and chronic kidney disease (CKD) is currently unknown. We showed that the major profibrotic cytokine, TGF-β1 promoted rapid Rac1-GTP loading in human kidney 2 (HK-2) human renal epithelial cells.

Role of nerve block as a diagnostic tool in pudendal nerve entrapment.

Background: Pudendal nerve entrapment is a disabling condition which is difficult to diagnose and treat. Nantes criteria include the requirement of positive anaesthetic pudendal nerve block that is widely used to allow identification of patients likely to benefit from the definitive but invasive pudendal nerve release. This study aimed to determine if pudendal nerve blockade under general anaesthesia could diagnose and temporarily treat pudendal nerve entrapment in patients suffering from chronic pelvic/perineal pain and/or organ dysfunction.

Development and Validation of Machine Learning Models in Prediction of Remission in Patients With Moderate to Severe Crohn Disease.

Importance: Biological therapies have revolutionized inflammatory bowel disease management, but many patients do not respond to biological monotherapy. Identification of likely responders could reduce costs and delays in remission.

Objective: To identify patients with Crohn disease likely to be durable responders to ustekinumab before committing to long-term treatment.

Citrobacter rodentium Induces Tissue-Resident Memory CD4 T Cells.

Tissue-resident memory T cells (T cells) are a novel population of tissue-restricted antigen-specific T cells. T cells are induced by pathogens and promote host defense against secondary infections. Although T cells cannot be detected in circulation, they are the major memory CD4 and CD8 T-cell population in tissues in mice and humans.

Electronic Neurostatus-EDSS increases the quality of expanded disability status scale assessments: Experience from two phase 3 clinical trials.

Background: The Neurostatus-eEDSS is an electronic tool providing automated real-time feedback on inconsistencies of Neurostatus-EDSS calculations.

Objective: To analyze the performance of the Neurostatus-eEDSS in two multicenter phase 3 multiple sclerosis (MS) trials.

Methods: All assessments captured with the Neurostatus-eEDSS web service during a period of 2.

Serum Protein Biomarkers of Fibrosis Aid in Risk Stratification of Future Stricturing Complications in Pediatric Crohn's Disease.

Objectives: Avoiding fibrostenotic complications is of paramount concern in the management of Crohn's disease (CD). We sought to investigate the association of candidate biomarkers of fibrosis collected at diagnosis with the future development of fibrostenotic CD.

Methods: Using the Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn's Disease cohort, a multicenter prospective observational pediatric inception cohort, subjects with an inflammatory phenotype (B1) at diagnosis who later converted to a stricturing phenotype (B2) within 3 years were compared with those who remained B1.

Phenotypic and Genotypic Characterization of spp. Panel Strains: A Cornerstone to Facilitate Antimicrobial Development.

spp. have emerged as significant pathogens causing nosocomial infections. Treatment of these pathogens has become a major challenge to clinicians worldwide, due to their increasing tendency to antibiotic resistance.

Acinetobacter baumannii analysis by core genome multi-locus sequence typing in two hospitals in Bolivia: endemicity of international clone 7 isolates (CC25).

In total, 95 Acinetobacter baumannii isolates recovered from patients from two hospitals in Cochabamba, Bolivia were studied. The presence of class D and B β-lactamases was investigated using polymerase chain reaction, and antimicrobial susceptibility testing was performed by agar dilution and broth microdilution. The resistance rate to carbapenems was 53.

Efficacy of Fecal Microbiota Transplantation in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis.

Objectives: Irritable bowel syndrome (IBS) is a common gastrointestinal condition with a heterogeneous pathophysiology. An altered gut microbiome has been identified in some IBS patients, and fecal microbiota transplantation (FMT) has been suggested to treat IBS. We performed meta-analyses and systematic review of available randomized controlled trials (RCTs) to evaluate the efficacy of FMT in IBS.

The Impact of Raising the Bar for Clinical Trials in Ulcerative Colitis.

In order to identify the practical implications for both health care practitioners and patients in understanding differences between the results of trials assessing therapies for ulcerative colitis [UC], we reviewed clinical trials of therapies for moderate to severe UC, with a focus on trial design. Over time, patient populations in UC trials have become more refractory, reflecting that patients are failing treatment with additional and different classes of drug, including conventional therapies, immunosuppressant drugs, and anti-tumour necrosis factor therapies. Outcomes used to measure efficacy have become increasingly stringent in order to meet the expectations of patients and physicians, and the requirements of regulatory bodies.

Seasonal Occurrence and Carbapenem Susceptibility of Bovine in Germany.

is one of the leading causes of nosocomial infections in humans. To investigate its prevalence, distribution of sequence types (STs), and antimicrobial resistance in cattle, we sampled 422 cattle, including 280 dairy cows, 59 beef cattle, and 83 calves over a 14-month period. Metadata, such as the previous use of antimicrobial agents and feeding, were collected to identify putative determining factors.

Multi-state study of Enterobacteriaceae harboring extended-spectrum beta-lactamase and carbapenemase genes in U.S. drinking water.

Community-associated acquisition of extended-spectrum beta-lactamase- (ESBL) and carbapenemase-producing Enterobacteriaceae has significantly increased in recent years, necessitating greater inquiry into potential exposure routes, including food and water sources. In high-income countries, drinking water is often neglected as a possible source of community exposure to antibiotic-resistant organisms. We screened coliform-positive tap water samples (n = 483) from public and private water systems in six states of the United States for bla, bla, bla, bla, bla, and bla-type genes by multiplex PCR.

Identification of the novel class D β-lactamase OXA-679 involved in carbapenem resistance in Acinetobacter calcoaceticus.

Objectives: The aim of this study was to characterize the Acinetobacter calcoaceticus clinical isolate AC_2117 with the novel carbapenem-hydrolysing class D β-lactamase (CHDL) OXA-679.

Methods: Identification of the species and β-lactamases was verified by genome sequencing (PacBio) and phylogenetic analyses. Antibiotic susceptibility of AC_2117 and transformants harbouring cloned blaOXA-679 was evaluated using antibiotic gradient strips and microbroth dilution.

Flagellin-mediated activation of IL-33-ST2 signaling by a pathobiont promotes intestinal fibrosis.

Intestinal fibrosis is a severe complication in patients with Crohn's disease (CD). Unfortunately, the trigger leading to the development of intestinal fibrosis in the context of CD remains elusive. Here, we show that colonization by a CD-associated pathobiont adherent-invasive Escherichia coli (AIEC) promotes the development of intestinal fibrosis.