Use of a mobile application for self-management of pancreatic enzyme replacement therapy is associated with improved gastro-intestinal related quality of life in children with Cystic Fibrosis.

BACKGROUND: Most patients with cystic fibrosis (CF) suffer from pancreatic insufficiency (PI), leading to fat malabsorption, malnutrition, abdominal discomfort and impaired growth. Pancreatic enzyme replacement therapy (PERT) is effective, but evidence based guidelines for dose adjustment are lacking. A mobile app for self-management of PERT was developed in the context of the HORIZON 2020 project MyCyFAPP. It contains an algorithm to calculate individual PERT-doses for optimal fat digestion, based on in vitro and in vivo studies carried out in the same project. In addition, the app includes a symptoms diary, educational material, and it is linked to a web tool allowing health care professionals to evaluate patient's data and provide feedback. METHODS: A 6-month open label prospective multicenter interventional clinical trial was performed to assess effects of using the app on gastro-intestinal related quality of life (GI QOL), measured by the CF-PedsQL-GI (shortened, CF specific version of the Pediatric Quality of Life Inventory, Gastrointestinal Symptoms Module). RESULTS: One hundred and seventy-one patients with CF and PI between 2 and 18 years were recruited at 6 European CF centers. Self-reported CF-PedsQL-GI improved significantly from month 0 (M0) (84.3, 76.4-90.3) to month 6 (M6) (89.4, 80.35-93.5) (p< 0.0001). Similar improvements were reported by parents. Lower baseline CF-PedsQL-GI was associated with a greater improvement at M6 (p < 0.001). CONCLUSIONS: The results suggest that the MyCyFAPP may improve GI QOL for children with CF. This tool may help patients to improve self-management of PERT, especially those with considerable GI symptoms.

Multifactorial inhibition of lactobacilli against the respiratory tract pathogen Moraxella catarrhalis.

Probiotics, mainly lactic acid bacteria (LAB), are widely focused on gastrointestinal applications. However, recent microbiome studies indicate that LAB can be endogenous members of other human body sites such as the upper respiratory tract (URT). Interestingly, DNA-based microbiome research suggests an inverse correlation between the presence of LAB and the occurrence of potential pathogens, such as Moraxella catarrhalis, an important URT pathogen linked to otitis media, sinusitis and chronic obstructive pulmonary disease. However, a direct interaction between these microbes has not been explored in detail. This study investigated the direct antipathogenic effects of Lactobacillus species, including several well-documented probiotic strains, on M. catarrhalis using agar-based assays, time course analysis, biofilm assays and minimal inhibitory concentration (MIC) testing. These assays were performed using spent culture supernatans (SCS) at two pHs (4.3 and 7) and D- and/or L-lactic acid at three pHs (2, 4 and 7). In addition, cell line assays for adhesion competition and immunomodulation were used to substantiate the inhibitory effect of lactobacilli against M. catarrhalis. A proportion of Lactobacillus strains, including the model probiotic Lactobacillus rhamnosus GG, showed a strong and direct activity against M. catarrhalis. Screening of the activity of the SCS after different treatments demonstrated that lactic acid has an important antimicrobial activity against this pathogen - at least in vitro - with mean MIC values for D- and L-lactic acid varying between 0.5 and 27 g/l depending on the pH. Furthermore, L. rhamnosus GG also decreased the adhesion of M. catarrhalis to human airway epithelial Calu-3 cells with more than 50%, and the expression of mucin MUC5AC, pro-inflammatory cytokines interleukin (IL)-8, IL-1ß, and tumor necrosis factor-α at least 1.2 fold. This study suggests that several lactobacilli and their key metabolite lactic acid are possible candidates for probiotic therapeutic interventions against URT infections.

FISH analysis of Lactobacillus biofilms in the gastrointestinal tract of different hosts.

AIMS: To investigate the spatial organization of endogenous and exogenously applied Lactobacillus communities at specific locations in the adult gastrointestinal tract of different hosts. METHODS AND RESULTS: Samples of the human, murine and avian gastrointestinal tract of subjects that received or not received a Lactobacillus probiotic were analysed by fluorescence in situ hybridization (FISH) with rRNA-targeted probes. High levels of endogenous lactobacilli were observed on the nonsecretory, stratified squamous epithelia present in the forestomach of mice and crop of chickens, respectively. These epithelial associations showed characteristics of bacterial biofilms, i.e. bacteria attached to a surface and embedded in a matrix of extracellular polymeric substances. In other regions of the analysed intestines, lactobacilli seemed to occur mainly as dispersed bacterial cells or as microcolonies. Exogenous administration of a Lactobacillus probiotic did increase the levels of loosely adherent Lactobacillus cells detected. However, the probiotic strains were unable to establish themselves inside the gastrointestinal biofilms. CONCLUSIONS: Gastrointestinal biofilms of lactobacilli occur only in specific niches in certain hosts, such as the murine forestomach and avian crop. SIGNIFICANCE AND IMPACT OF THE STUDY: Biofilm formation by lactobacilli in specific parts of animal gastrointestinal tracts was documented for the first time by FISH.

Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis.

While some probiotic strains might have adjuvant effects in the therapy for inflammatory bowel diseases (IBD), these effects remain controversial and cannot be generalized. In this study, a dltD mutant of the model probiotic Lactobacillus rhamnosus GG (LGG), having a drastic modification in its lipoteichoic acid (LTA) molecules, was analysed for its effects in an experimental colitis model. Dextran sulphate sodium (DSS) was used to induce either moderate to severe or mild chronic colitis in mice. Mice received either phosphate-buffered saline (PBS), LGG wild-type or the dltD mutant via the drinking water. Macroscopic parameters, histological abnormalities, cytokine and Toll-like receptor (TLR) expression were analysed to assess disease activity. LGG wild-type did not show efficacy in the different experimental colitis set-ups. This wild-type strain even seemed to exacerbate the severity of colitic parameters in the moderate to severe colitis model compared to untreated mice. In contrast, mice treated with the dltD mutant showed an improvement of some colitic parameters compared to LGG wild-type-treated mice in both experimental models. In addition, treatment with the dltD mutant correlated with a significant down-regulation of Toll-like receptor-2 expression and of downstream proinflammatory cytokine expression in the colitic mice. These results show that molecular cell surface characteristics of probiotics are crucial when probiotics are considered for use as supporting therapy in IBD.

Bacterial colonization of central airways after stenting.

Airway stenting (AS) is increasingly used in the management of obstructive lesions of the central airways. Although retention of secretions and infection have been reported as complications of AS, the microbiological consequences of AS have not yet been evaluated. In this study, we prospectively performed protected specimen brush (PSB) sampling of the airways, before and 3 to 4 wk after AS, in 14 consecutive patients (65 +/- 17 yr), suffering from bronchial (5), extensive esophageal (2), thyroid (1), and adenocystic (1) carcinoma, stenotic tracheal burn lesions (2), postintubation stenosis (2), and Wegener's granulomatosis (1). A cutoff value of >/= 10(2) colony-forming units (cfu). ml(-)(1) was considered diagnostic for airway colonization (AC). PSB results were related to the presence and degree of secretion retention (SR) at the level of the stent. In five of the 14 patients, AC was present prior to AS; in three of these, potentially pathogenic microorganisms (PPM) were identified. After AS, AC was found in 11 (including seven patients without prior AC) of the 14 patients. In six of these patients, one or more PPM were present (Pseudomonas aeruginosa [4], Staphylococcus aureus [3], Streptococcus pneumoniae [1], Klebsiella spp. [1]). Although AC tended to be associated with the presence of SR (PSB >/= 10(2) cfu. ml(-)(1) in 10 of 12 SR-positive and in zero SR-negative cases; PSB < 10(2) cfu. ml(-)(1) in two SR-positive and in two SR-negative cases), statistical significance was not reached (Fisher exact test, p = 0.06). We conclude that AS is frequently followed by AC, the majority of which occurs in patients without AC prior to AS, and is caused by PPM. In no case, however, AC was associated with clinical signs of infection. AC tended to be associated with SR in the stent.

Screw-thread vs Dumon endoprosthesis in the management of tracheal stenosis.

STUDY OBJECTIVES: A frequent complication of the widely used Dumon silicone stent is its tendency to migrate when used in tracheal stenosis. We compared the clinical efficacy and complications (including migration) of the Dumon stent with a screw-thread stent, a device with an increased stent-to-wall contact surface and, theoretically, less tendency to migrate. DESIGN: Retrospective case analysis. SETTING: Academic hospital. MATERIALS AND METHODS: Forty-six patients with tracheal stenoses (23 benign and 23 malignant) requiring the placement of 50 stents (29 Dumon and 21 screw-thread) were studied. In 26 patients Dumon stents were used, and in 20 patients screw-thread stents were used. Both patient groups had comparable clinical and stenosis-related characteristics. RESULTS: Stent insertion and follow-up were uneventful in both the Dumon and the screw-thread insertions, respectively: 62% vs 67% (not significant). There were seven migrations in the Dumon group, compared to only one migration in the screw-thread group, respectively: 24% vs 5%. This difference did not reach statistical significance (p = 0.1). All of the migrations occurred in the benign stenosis group, and none occurred in the malignant-stenosis group, respectively: 8 of 23 vs 0 of 23, p = 0.004. Within the benign-stenosis group, the Dumon stent had a significantly increased risk for migration when compared to the screw-thread stent, respectively: 7 of 13 vs 1 of 11, p = 0.033. CONCLUSIONS: The screw-thread stent and the Dumon stent are equally effective in the management of tracheal stenosis. There is a general trend toward a decreased migration rate, and a significantly lower risk for migration in patients with benign tracheal stenosis. The (less expensive) screw-thread stent may represent an attractive alternative in the management of tracheal stenosis in general, and may be preferable to the Dumon stent in treating benign tracheal stenosis.

Crystal Structure of N,N-Dimethylthioformamide Solvates of the Divalent Group 12 Ions with Linear Coordination Geometry for Mercury(II), Tetrahedral for Zinc(II), and Octahedral for Cadmium(II).

The crystalline solvates of the divalent group 12 metal ions with the soft sulfur donor N,N-dimethylthioformamide display an unusual variation in coordination number and geometry with two, four, and six ligands attached to the mercury(II), zinc(II), and cadmium(II), ions, respectively. Bis(N,N-dimethylthioformamide)mercury(II) perchlorate precipitates from acetonitrile solution when adding less than 2 equiv of N,N-dimethylthioformamide, while the zinc and cadmium solvates crystallize from saturated N,N-dimethylthioformamide solutions. The disolvate [Hg(SCHN(CH(3))(2))(2)](ClO(4))(2) crystallizes in the monoclinic space group P2(1)/n (No. 14) with a = 6.208(1) Å, b = 15.239(7) Å, c = 8.681(2) Å, beta = 99.30(3) degrees, and Z = 2. Centrosymmetric mercury(II) complexes with strong collinear bonds to two N,N-dimethylthioformamide molecules, Hg-S 2.350(2) Å, are joined by double bridges of perchlorate ions in chains along the a-axis by four weak interactions between the mercury and the perchlorate oxygen atoms, mean Hg-O distance 2.84 Å. Tetrakis(N,N-dimethylthioformamide)zinc trifluoromethanesulfonate, [Zn(SCHN(CH(3))(2))(4)](CF(3)SO(3))(2), crystallizes in the triclinic space group P&onemacr; (No. 2) with a = 10.487(3) Å, b = 12.910(3) Å, c = 13.489(5) Å, alpha = 68.800(4) degrees, beta = 69.260(4) degrees, gamma = 74.06(1) degrees, and Z = 2, with the zinc ions tetrahedrally surrounded by four N,N-dimethylthioformamide ligands, mean Zn-S distance 2.34 Å. Also the cadmium solvate of corresponding composition, [Cd(SCHN(CH(3))(2))(4)(CF(3)SO(3))(2)], crystallizes in the space group P&onemacr;, with a = 8.670(1) Å, b = 9.529(1) Å, c = 10.685(1) Å, alpha = 75.20(1) degrees, beta = 66.97(1) degrees, gamma = 65.31(1) degrees, and Z = 1, although the structure comprises centrosymmetric tetrakis(N,N-dimethylthioformamide)bis(trifluoromethanesulfonato)cadmium(II) complexes in which four Cd-S bonds (mean 2.65 Å) and two weaker Cd-O bonds at 2.470(2) Å to the trifluoromethanesulfonate ions give rise to a pseudo-octahedral coordination around the cadmium ion. When using perchlorate instead as counterion, hexakis(N,N-dimethylthioformamide)cadmium perchlorate, [Cd(SCHN(CH(3))(2))(6)](ClO(4))(2), crystallizes in the space group P2(1)/n with a = 12.757(1) Å, b = 7.4681(6) Å, c = 19.732(2) Å, beta = 96.31(1) degrees, and Z = 2. The mean Cd-S bond distance increases to 2.715 Å in the fully solvated cadmium ion with almost regular octahedral coordination geometry to its six centrosymmetrically related ligands. The effect of the weak internal hydrogen bonding occuring between the hydrogen atom of a -CHS group and the sulfur atom of neighboring N,N-dimethylthioformamide ligands is discussed.

Three cases of bronchial stump aspergillosis: unusual clinical presentations and beneficial effect of oral itraconazole.

Bronchial stump aspergillosis (BSA), i.e. Aspergillus infection of bronchial granulation tissue surrounding endobronchial suture threads, is a very rare variant of localized suppurative bronchial Aspergillus infection. The majority of reported cases have occurred within one year after lung surgery. We present three more patients, in whom BSA occurred very late (4.5, 6 and 7 yrs) after pulmonary resection. Other unusual features were: complete absence of symptoms in one patient, and simultaneous occurrence of aspergilloma in another. Removal of the endobronchial suture probably constitutes the key therapy for BSA. In all three of our patients oral itraconazole resulted in clinical, histological and microbiological improvement. In conclusion, BSA should be considered in the differential diagnosis of haemoptysis occurring up to 7 yrs after lung surgery, although an asymptomatic presentation is possible. Furthermore, BSA can be associated with other clinical presentations of Aspergillus infection, e.g. aspergilloma. Finally, long-term oral itraconazole therapy may represent a valid alternative when removal of the suture is not feasible.