Nonmicrobial activation of TLRs controls intestinal growth, wound repair, and radioprotection

TLRs, key components of the innate immune system, recognize microbial molecules. However, TLRs also recognize some nonmicrobial molecules. In particular, TLR2 and TLR4 recognize hyaluronic acid, a glycosaminoglycan in the extracellular matrix. In neonatal mice endogenous hyaluronic acid binding to TLR4 drives normal intestinal growth. Hyaluronic acid binding to TLR4 in pericryptal macrophages results in cyclooxygenase2- dependent PG

Rectal budesonide and mesalamine formulations in active ulcerative proctosigmoiditis: efficacy, tolerance, and treatment approach

Ulcerative colitis (UC) is an immune-mediated disease of the colon that is characterized by diffuse and continuous inflammation contiguous from the rectum. Half of UC patients have inflammation limited to the distal colon (proctitis or proctosigmoiditis) that primarily causes symptoms of bloody diarrhea and urgency. Mild-to-moderate distal UC can be effectively treated with topical formulations (rectal suppositories, enemas, or foam) of mesalamine or steroids to reduce mucosal inflammation and alleviate symptoms. Enemas or foam formulations adequately reach up to the splenic flexure, have a minimal side-effect profile, and induce remission alone or in combination with systemic immunosuppressive therapy. Herein, we compare the efficacy, cost, patient tolerance, and side-effect profiles of steroid and mesalamine rectal formulations in distal UC. Patients with distal mild-to-moderate UC have a remission rate of approximately 75% (NNT =2) after treatment for 6 weeks with mesalamine enemas. Rectal budesonide foam induces remission in 41.2% of patients with mild-to-moderate active distal UC compared to 24% of patient treated with placebo (NNT =5). However, rectal budesonide has better patient tolerance profile compared to enema formulations. Despite its favorable efficacy, safety, and cost profiles, patients and physicians significantly underuse topical treatments for treating distal colitis. This necessitates improved patient education and physician familiarity regarding the indications, effectiveness, and potential financial and tolerability barriers in using rectal formulations

Highly conserved type 1 pili promote enterotoxigenic E. coli pathogen-host interactions

Enterotoxigenic Escherichia coli (ETEC), defined by their elaboration of heat-labile (LT) and/or heat-stable (ST) enterotoxins, are a common cause of diarrheal illness in developing countries. Efficient delivery of these toxins requires ETEC to engage target host enterocytes. This engagement is accomplished using a variety of pathovar-specific and conserved E. coli adhesin molecules as well as plasmid encoded colonization factors. Some of these adhesins undergo significant transcriptional modulation as ETEC encounter intestinal epithelia, perhaps suggesting that they cooperatively facilitate interaction with the host. Among genes significantly upregulated on cell contact are those encoding type 1 pili. We therefore investigated the role played by these pili in facilitating ETEC adhesion, and toxin delivery to model intestinal epithelia. We demonstrate that type 1 pili, encoded in the E. coli core genome, play an essential role in ETEC virulence, acting in concert with plasmid-encoded pathovar specific colonization factor (CF) fimbriae to promote optimal bacterial adhesion to cultured intestinal epithelium (CIE) and to epithelial monolayers differentiated from human small intestinal stem cells. Type 1 pili are tipped with the FimH adhesin which recognizes mannose with stereochemical specificity. Thus, enhanced production of highly mannosylated proteins on intestinal epithelia promoted FimH-mediated ETEC adhesion, while conversely, interruption of FimH lectin-epithelial interactions with soluble mannose, anti-FimH antibodies or mutagenesis of fimH effectively blocked ETEC adhesion. Moreover, fimH mutants were significantly impaired in delivery of both heat-stable and heat-labile toxins to the target epithelial cells in vitro, and these mutants were substantially less virulent in rabbit ileal loop assays, a classical model of ETEC pathogenesis. Collectively, our data suggest that these highly conserved pili play an essential role in virulence of these diverse pathogens

Malignant otitis externa in the antibiotic resistance era: key to successful treatment

Malignant otitis externa in the antibiotic resistance era: key to successful treatment. Objective: Malignant otitis externa (MOE) is a rare aggressive, necrotizing infection of the external auditory canal and the temporal bone. MOE may have a poor prognosis when it is not treated promptly and adequately. It is most commonly reported in males, older individuals, patients with diabetes, or patients that are immunocompromised. Pseudomonas aeruginosa is the main pathogenic agent involved. This study aimed to evaluate a clinical series of patients with MOE and discuss the current literature on the topic. Methodology: This retrospective study included 8 patients with MOE that were evaluated and treated, medically and/ or surgically, at the University Hospital of Ferrara between January 2012 and December 2016. We retrieved data from medical records on the clinical history, imaging, and treatment. Results: In all cases, a microbiological examination disclosed the presence of P. aeruginosa. The infection was eventually controlled in all cases, after a median of 6 months of therapy. All patients were followed-up for an average of 12 months after infection resolution. Conclusion: Currently, no specific guidelines for MOE treatment are available in the literature. Based on our findings, we proposed a diagnostic and therapeutic flow-chart for managing this infection

Systematic review with meta-analysis: Safety and effectiveness of combining biologics and small molecules in inflammatory bowel disease

BACKGROUND: Combining biologics and small molecules could potentially overcome the plateau of drug efficacy in inflammatory bowel disease (IBD). We conducted a systematic review and meta-analysis to assess the safety and effectiveness of dual biologic therapy (DBT), or small molecule combined with a biologic therapy (SBT) in IBD patients. METHODS: We searched MEDLINE, EMBASE, Scopus, Web of Science, Cochrane Database of Systematic Reviews, and Clinical trials.gov until November 3, 2020, including studies with 2 or more IBD patients on DBT or SBT. Main outcome was safety assessed as pooled rates of adverse events (AEs) and serious AEs (SAEs) for each combination. Effectiveness was reported as pooled rates of clinical, endoscopic, and/or radiographic response and remission. The certainty of evidence was rated according to the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework. RESULTS: Of the 3688 publications identified, 13 studies (1 clinical trial, 12 observational studies) involving 266 patients on 7 different combinations were included. Median number of prior biologics ranged from 0 to 4, and median duration of follow-up was 16-68 weeks. Most common DBT and SBT were vedolizumab (VDZ) with anti-tumor necrosis factor (aTNF, CONCLUSIONS: DBT or SBT appears to be generally safe and may be effective in IBD patients, but the evidence is very uncertain

Bilateral osseous stenosis of the internal auditory canal: case report

Osteomas as well as exostoses of the internal auditory canal are rare, benign, usually slow-growing lesions. The most common localizations of these temporal bone lesions are the mastoid cortex and the external auditory canal. A rare case is reported of bilateral osseous stenosis of the internal auditory canal, in the absence of clinical (auditory, vestibular and facial nerve) symptoms. In the absence of auditory, vestibular and/or facial nerve symptoms, long-term follow-up should be assessed; surgical intervention may be warranted only if symptoms are present

Vertigo and dizziness in children: An update

Background: Vertigo and dizziness are relatively infrequent in paediatric patients, but specific data on the prevalence of these disorders are limited and influenced by various factors, including the age of the examined population. These conditions often have a significant impact on patients’ and parents’ quality of life. The aim of this paper is to investigate the prevalence of different aetiologies of vertigo in the paediatric population through a systematic review. Methods: According to PRISMA guidelines, a systematic review of the literature was performed. Medline and Embase were searched from January 2011 through to 10 September 2021. The search yielded 1094 manuscripts, which were reduced to 7 upon the application of inclusion criteria. Results: A total of 2470 paediatric patients were evaluated by the selected papers. Vestibular Migraine was the most frequently diagnosed condition, occurring alone or in association with other diseases. Overall, audio-vestibular disorders represented the second cause of vertigo, and the prevalence appears to increase according to age growth. Over the years, even though we assisted in the amelioration of diagnostic rates, partially related to an improvement in diagnostic tools, the aetiology of vertigo remains still unclear in a variable percentage of patients. Conclusion: Vertigo in children, despite being an uncommon symptom, requires a multidisciplinary approach, often involving Paediatricians, Neurologists and Otorhinolaryngologists. A comprehensive evaluation of children suffering from vertigo is crucial for establishing a successful therapy and reducing parental worries