Clonal spread of antimicrobial-resistant Escherichia coli isolates among pups in two kennels

Although the dog breeding industry is common in many countries, the presence of antimicrobial resistant bacteria among pups in kennels has been infrequently investigated. This study was conducted to better understand the epidemiology of antimicrobial-resistant Escherichia coli isolates from kennel pups not treated with antimicrobials. We investigated susceptibilities to 11 antimicrobials, and prevalence of extended-spectrum β-lactamase (ESBL) in 86 faecal E. coli isolates from 43 pups in two kennels. Genetic relatedness among all isolates was assessed using pulsed-field gel electrophoresis (PFGE). Susceptibility tests revealed that 76% of the isolates were resistant to one or more of tested antimicrobials, with resistance to dihydrostreptomycin most frequently encountered (66.3%) followed by ampicillin (60.5%), trimethoprim-sulfamethoxazole (41.9%), oxytetracycline (26.7%), and chloramphenicol (26.7%). Multidrug resistance, defined as resistance against two or more classes of antimicrobials, was observed in 52 (60.5%) isolates. Three pups in one kennel harboured SHV-12 ESBL-producing isolates. A comparison between the two kennels showed that frequencies of resistance against seven antimicrobials and the variation in resistant phenotypes differed significantly. Analysis by PFGE revealed that clone sharing rates among pups of the same litters were not significantly different in both kennels (64.0% vs. 88.9%), whereas the rates among pups from different litters were significantly different between the two kennels (72.0% vs. 33.3%, P < 0.05). The pups in the two kennels had antimicrobial-resistant E. coli clones, including multidrug-resistant and ESBL-producing clones. It is likely that resistant and susceptible bacteria can clonally spread among the same and/or different litters thus affecting the resistance prevalence

Experimental Pulmonary Granuloma Mimicking Sarcoidosis Induced by Propionibacterium acnes in Mice

Propionibacterium acnes has been implicated as an etiologic agent of sarcoidosis since the isolation of this bacterium from sarcoid lesions. We experimentally produced a murine pulmonary granuloma model using P. acnes with several features that simulate sarcoidosis. Mice were sensitized with heat-killed P. acnes and complete Freund's adjuvant and were subsequently challenged with heat-killed P. acnes at 2-week intervals. P. acnes-challenged mice developed epitheloid cell granulomas in the lungs. These mice showed a pulmonary immune response characterized by an increased number of T-lymphocytes, especially CD4 cells, and the ratio of CD4/CD8 in bronchoalveolar lavage (BAL) fluid also increased. Furthermore, significant elevations in both angiotensin-converting enzyme (ACE) serum levels and antibody titers against P. acnes were observed. Mice sensitized with P. acnes without complete Freund's adjuvant were capable of forming pulmonary granulomas, which appeared to be caused by indigenous P. acnes. The genome of P. acnes was found in the lungs, BAL cells, hilar lymph nodes, liver, and spleen in non-sensitized mice, which were thought to be germ-free. These results suggest that the immune response against indigenous P. acnes may play an important role in the pathogenesis of granuloma formation in a murine model.</p

Around ten percent of most recent Cochrane reviews included outcomes in their literature search strategy and were associated with potentially exaggerated results: A research-on-research study

[Objectives] To assess the proportion of the recent Cochrane reviews that included outcomes in their literature search strategy, how often they acknowledged these limitations, and how qualitatively different the results of outcomes included and not included in the search strategy were. [Design and Setting] We identified all the Cochrane reviews of the interventions published in 2020 that used a search strategy connecting outcome terms with “AND.” Reviews were defined as acknowledging the limitations of searching for outcomes if they mentioned them in the discussion. We compared the characteristics of outcomes included and not included in the search strategy. [Results] Of the 523 Cochrane reviews published in 2020, 51 (9.8%) included outcomes in their search strategy. Only one review acknowledged it as a limitation. Forty-seven (92%) assessed outcomes not included in the search strategy. Outcomes included in the search strategies tended to include a larger number of studies and show their effects in favor of the intervention. [Conclusions] Around ten percent of the recent Cochrane reviews included outcomes in their search, which may have resulted in more outcomes significantly in favor of the intervention. Reviewers should be more explicit in acknowledging the potential implications of searching for outcomes

The impact of continuity correction methods in Cochrane reviews with single-zero trials with rare events: A meta-epidemiological study.

Meta-analyses examining dichotomous outcomes often include single-zero studies, where no events occur in intervention or control groups. These pose challenges, and several methods have been proposed to address them. A fixed continuity correction method has been shown to bias estimates, but it is frequently used because sometimes software (e.g., RevMan software in Cochrane reviews) uses it as a default. We aimed to empirically compare results using the continuity correction with those using alternative models that do not require correction. To this aim, we reanalyzed the original data from 885 meta-analyses in Cochrane reviews using the following methods: (i) Mantel-Haenszel model with a fixed continuity correction, (ii) random effects inverse variance model with a fixed continuity correction, (iii) Peto method (the three models available in RevMan), (iv) random effects inverse variance model with the treatment arm continuity correction, (v) Mantel-Haenszel model without correction, (vi) logistic regression, and (vii) a Bayesian random effects model with binominal likelihood. For each meta-analysis we calculated ratios of odds ratios between all methods, to assess how the choice of method may impact results. Ratios of odds ratios <0.8 or <1.25 were seen in ~30% of the existing meta-analyses when comparing results between Mantel-Haenszel model with a fixed continuity correction and either Mantel-Haenszel model without correction or logistic regression. We concluded that injudicious use of the fixed continuity correction in existing Cochrane reviews may have substantially influenced effect estimates in some cases. Future updates of RevMan should incorporate less biased statistical methods

Retracted randomised controlled trials were cited and not corrected in systematic reviews and clinical practice guidelines

[Background and Objectives] To investigate whether and when the correction is done in Systematic Reviews (SRs) and Clinical Practice Guidelines (CPGs) when included Randomized Controlled Trials (RCTs) have been retracted. [Methods] In this meta-epidemiological study, we included SRs and CPGs citing the retracted RCTs from the Retraction Watch Database. We investigated how often the retracted RCTs were cited in SRs and CPGs. We also investigated whether and when such SRs and CPGs corrected themselves. [Results] We identified 587 articles (525 SRs and 62 CPGs) citing retracted RCTs. Among the 587 articles, 252 (43%) were published after retraction, and 335 (57%) were published before retraction. Among 127 articles published citing already retracted RCTs in their evidence synthesis without caution, none corrected themselves after publication. Of 335 articles published before retraction, 239 included RCTs that were later retracted in their evidence synthesis. Among them, only 5% of SRs (9/196) and 5% of CPGs (2/43) corrected or retracted their results. [Conclusion] Many SRs and CPGs included already or later retracted RCTs without caution. Most of them were never corrected. The scientific community, including publishers and researchers, should make systematic and concerted efforts to remove the impact of retracted RCTs

Efficacy and Safety of Three-dimensional Conformal Radiotherapy for Macroscopic Vascular Invasion of Hepatocellular Carcinoma

Chemotherapy is insufficient to treat macroscopic vascular invasion (MVI) of hepatocellular carcinoma (HCC). We retrospectively investigated the treatment outcomes of patients who underwent three-dimensional conformal radiotherapy (3D-CRT) for HCC MVI and analyzed prognostic factors by multivariate analysis using a Cox proportional hazard model. Sixty-five patients were studied. MVI sites were the portal vein (n=48 patients), portal and hepatic veins (n=8), and hepatic vein (n=9). The median irradiation dose was 50 Gy. The median survival time (MST) was 7.5 months. Performance status 2 or 3, modified albumin-bilirubin grade 2b or 3, and massive/diffuse type were poor prognostic factors. Nineteen patients (29%) with a treatment effect of 3 or 4 (≥ 50% of tumor necrosis or regression) at the irradiation sites according to the Response Evaluation Criteria in Cancer of the Liver showed longer survival than those with an effect of 1 or 2 (MST 18.7 vs. 5.9 months, p<0.001). No treatment-related death occurred. The hepatic function reserve was preserved in more than 70% of patients. 3D-CRT controlled HCC MVI safely and was suggested to be a good treatment option

Preoperative obliteration of choroidal arteries in the treatment of large hypervascular tumors in the lateral ventricle

BACKGROUND: Removal of large hypervascular tumors in the lateral ventricle still poses a surgical challenge. These tumors are usually fed from choroidal arteries, and vascular control is typically performed late during the removal. We aimed to evaluate the clinical efficacy of our strategy for persistent preoperative obliteration of feeders from the choroidal arteries to manage large hypervascular tumors in the lateral ventricle. METHODS: We retrospectively analyzed six patients with hypervascular tumors in the lateral ventricle. We first attempted to obstruct feeders using endovascular treatment, and, if unavailable, performed initial microsurgical occlusion through the temporal horn for the staged tumor removal. RESULTS: In all patients, feeder obliteration was successfully performed; the anterior choroidal arteries were occluded by the endovascular treatment and microsurgical occlusion in one and five patients, respectively, while the lateral posterior choroidal arteries were occluded via endovascular treatment in four patients. No patients had permanent symptoms due to feeder obliteration, and tumor devascularization was achieved at the mean rate of 69.9%. During the tumor removal, the mean blood loss volume was 253 ml. No postoperative hemorrhage had occurred, and all patients scored ≤ 2 on the modified Rankin Scale at six months post-removal. CONCLUSIONS: Although further studies are warranted, persistent feeder obliteration of choroidal arteries could be an effective treatment strategy against large hypervascular tumors in the lateral ventricle

Inhibition of neutrophil elastase attenuates airway hyperresponsiveness and inflammation in a mouse model of secondary allergen challenge: neutrophil elastase inhibition attenuates allergic airway responses

Background: Chronic asthma is often associated with neutrophilic infiltration in the airways. Neutrophils contain elastase, a potent secretagogue in the airways, nonetheless the role for neutrophil elastase as well as neutrophilic inflammation in allergen-induced airway responses is not well defined. In this study, we have investigated the impact of neutrophil elastase inhibition on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in previously sensitized and challenged mice. Methods: BALB/c mice were sensitized and challenged (primary) with ovalbumin (OVA). Six weeks later, a single OVA aerosol (secondary challenge) was delivered and airway inflammation and airway responses were monitored 6 and 48 hrs later. An inhibitor of neutrophil elastase was administered prior to secondary challenge. Results: Mice developed a two-phase airway inflammatory response after secondary allergen challenge, one neutrophilic at 6 hr and the other eosinophilic, at 48 hr. PAR-2 expression in the lung tissues was enhanced following secondary challenge, and that PAR-2 intracellular expression on peribronchial lymph node (PBLN) T cells was also increased following allergen challenge of sensitized mice. Inhibition of neutrophil elastase significantly attenuated AHR, goblet cell metaplasia, and inflammatory cell accumulation in the airways following secondary OVA challenge. Levels of IL-4, IL-5 and IL-13, and eotaxin in BAL fluid 6 hr after secondary allergen challenge were significantly suppressed by the treatment. At 48 hr, treatment with the neutrophil elastase inhibitor significantly reduced the levels of IL-13 and TGF-beta 1 in the BAL fluid. In parallel, in vitro IL-13 production was significantly inhibited in spleen cells from sensitized mice. Conclusion: These data indicate that neutrophil elastase plays an important role in the development of allergic airway inflammation and hyperresponsiveness, and would suggest that the neutrophil elastase inhibitor reduced AHR to inhaled methacholine indicating the potential for its use as a modulator of the immune/inflammatory response in both the neutrophil-and eosinophil-dominant phases of the response to secondary allergen challenge