Pseudomonas aeruginosa opportunistically infects the airways of patients with cystic fibrosis and causes significant morbidity and mortality. Initial infection can often be eradicated though requires prompt detection and adequate treatment. Intermittent and then chronic infection occurs in the majority of patients. Better detection of P. aeruginosa infection using biomarkers may enable more successful eradication before chronic infection is established. In chronic infection P. aeruginosa adapts to avoid immune clearance and resist antibiotics via efflux pumps, β-lactamase expression, reduced porins and switching to a biofilm lifestyle. The optimal treatment strategies for P. aeruginosa infection are still being established, and new antibiotic formulations such as liposomal amikacin, fosfomycin in combination with tobramycin and inhaled levofloxacin are being explored. Novel agents such as the alginate oligosaccharide OligoG, cysteamine, bacteriophage, nitric oxide, garlic oil and gallium may be useful as anti-pseudomonal strategies, and immunotherapy to prevent infection may have a role in the future. New treatments that target the primary defect in cystic fibrosis, recently licensed for use, have been associated with a fall in P. aeruginosa infection prevalence. Understanding the mechanisms for this could add further strategies for treating P. aeruginosa in future.

We report the case of a 72-year-old female renal transplant recipient with a nodular lesion in the distal phalange of the third left finger produced by a dematiaceous fungus that was identified as Phomopsis longicolla. She was treated with itraconazole and terbinafine and later with voriconazole, without response. The patient underwent a surgical resection with lesion-free edge and continued on voriconazole. One year later she was asymptomatic and had not developed new lesions.

Molecular clocks that record cell ancestry mutate too slowly to measure the short-timescale dynamics of cell renewal in adult tissues. Here, we show that fluctuating DNA methylation marks can be used as clocks in cells where ongoing methylation and demethylation cause repeated ‘flip–flops’ between methylated and unmethylated states. We identify endogenous fluctuating CpG (fCpG) sites using standard methylation arrays and develop a mathematical model to quantitatively measure human adult stem cell dynamics from these data. Small intestinal crypts were inferred to contain slightly more stem cells than the colon, with slower stem cell replacement in the small intestine. Germline APC mutation increased the number of replacements per crypt. In blood, we measured rapid expansion of acute leukemia and slower growth of chronic disease. Thus, the patterns of human somatic cell birth and death are measurable with fluctuating methylation clocks (FMCs).

The treatment of lung infection in the context of cystic fibrosis (CF) is limited by a biofilm mode of growth of pathogenic organisms. When compared to planktonically grown bacteria, bacterial biofilms can survive extremely high levels of antimicrobials. Within the lung, bacterial biofilms are aggregates of microorganisms suspended in a matrix of self-secreted proteins within the sputum. These structures offer both physical protection from antibiotics as well as a heterogeneous population of metabolically and phenotypically distinct bacteria. The bacteria themselves and the components of the extracellular matrix, in addition to the signaling pathways that direct their behaviour, are all potential targets for therapeutic intervention discussed in this review. This review touches on the successes and failures of current anti-biofilm strategies, before looking at emerging therapies and the mechanisms by which it is hoped they will overcome current limitations.

The population-based incidence of rotavirus gastroenteritis in children <5 years of age in Valencia, Spain, over a 1-year period (December 1, 2003, to November 30, 2004) was determined.A total of 553 episodes of gastroenteritis in children <5 years of age (mean age, 22.8 +/- 14.5 months) were recorded (annual incidence of 138 per 1,000). A positive enzyme-linked immunoadsorbant assay result for rotavirus antigen was obtained in 15% of the samples. The incidence of rotavirus gastroenteritis was 15 per 1,000 children <5 years of age, being the highest incidence in children

Cystic fibrosis is characterized by bacterial lung infection, a majority of adults being chronically infected with Pseudomonas aeruginosa. Treatment is a major challenge, with frequent courses of antibiotics contributing to antimicrobial resistance. New approaches are clearly required. Over the last few years, a major shift in our approach to treating CF has occurred with the availability of the first drugs targeting the CFTR protein and leading to improvements in lung function, weight gain and frequency of exacerbations. Areas covered: There are emerging, but limited, data exploring the effect these drugs have on airway infections, some studies suggesting a beneficial impact. CFTR modulators probably possess very little direct antimicrobial activity, but both synergy with conventional antibiotics and alternative mechanisms of bacterial killing have been proposed. This article reviews the current published evidence. Expert opinion: The picture is far from clear concerning the impact of CFTR modulators on lung infections. However, currently, such drugs restore CFTR function incompletely, are most commonly introduced when lung damage is already present, are not suitable for all CF patients and not reimbursed in some areas. Therefore, whatever their eventual anti-infective potential, we need to continue our search for effective anti-pseudomonal therapies for the foreseeable future.

Aim: Total colectomy with ileorectal anastomosis (TC-IRA) is a surgical option for patients with familial adenomatous polyposis (FAP). Regular endoscopic surveillance of the rectum is recommended to prevent rectal cancer. We aimed to document polyp progression in the rectum following TC-IRA and evaluate the role of polypectomy during surveillance. Method:Patients with FAP who underwent TC-IRA between 1990 and 2017 were identified. Demographic, endoscopic and genetic data were retrieved. Cumulative rectal adenoma (polyp) counts were obtained, whilst accounting for any polypectomies during the study period. The rate of polyp progression and factors influencing secondary proctectomy were evaluated.Results: One hundred and ninety-nine patients fulfilled our inclusion criteria, of which 44% were male. The median age at colectomy was 19 (range 11-70) years and median preoperative rectal polyp count was 7 (range 0-50). All patients had an APC pathogenic variant, of which 151 (79%) were 5' of the mutation cluster region (MCR), 19 (10%) in the MCR, six (3%) were 3' of the MCR and 15 (8%) had a gross deletion. After a median followup of 8.6 (range1-27) years and a median of 11 (range 2-37) flexible sigmoidoscopies per patient, the median rate of polyp progression was 5.5 polyps/year (range 0-70.2). There was no evidence of polyp regression. Eight (4%) patients underwent secondary proctectomy for neoplasia, of which one (0.5%) had rectal adenocarcinoma. A total of 13,527 polyps were removed, a median of 35 polyps/patient (range 0-829). The rate of polyp progression was not significantly associated with genotypic or phenotypic factors. Conclusion:Progression of rectal adenoma burden following TC-IRA appears to be slow and dependent on the length of follow-up. In the modern era of stringent endoscopic surveillance and therapeutic procedures such as cold snare polypectomy, the rate of secondary proctectomy and the risk of rectal cancer after TC-IRA are very low. These findings are important when counselling patients with regard to the choice of surgery for FAP and implementing endoscopic surveillance.

Background Patients with familial adenomatous polyposis (FAP) are at increased risk of developing gastric adenomas. There is limited understanding of their clinical course and no consensus on management. We reviewed the management of gastric adenomas in patients with FAP from two centres. Patients and methods Patients with FAP and histologically confirmed gastric adenomas were identified between 1997-2018. Patient demographics, adenoma characteristics management/surveillance outcomes were collected. Results One hundred and four (49 female) of 726 patients (14%) were diagnosed with gastric adenomas at a median age of 47 years (range 19-80). The median size of gastric adenoma was 6mm (range 1.5-50mm); 64 (62%) patients had adenomas located distal to the incisura. Five (5%) patients had gastric adenomas demonstrating high grade dysplasia (HGD) on initial diagnosis, distributed equally within the stomach. The risk of HGD was associated with adenoma size (p=0.04). Of adenomas larger than 20mm, 33% contained HGD. Two patients had gastric cancer at initial gastric adenoma diagnosis. Sixty-three (61%) patients underwent endoscopic therapy for gastric adenomas. Complications occurred in three (5%) patients and two (3%) had recurrence, all following piecemeal resection of large (30-50mm) lesions. Three patients were diagnosed with gastric cancer during follow-up, a median of 66 months (range 66-115) after initial diagnosis. Conclusions In this series, we observed gastric adenomas in 14% of patients with FAP. Five per cent contained HGD; risk of HGD correlated with adenoma size. Endoscopic resection was feasible, with few complications and low recurrence rates, but does not completely eliminate the cancer risk.