PURPOSE OF REVIEWProbiotics may prevent Clostridium difficile infection (CDI), a leading healthcare-associated infection in the United States. However, prior studies were limited by heterogeneity in ...products and patient populations. Recent clinical evidence and new approaches to probiotic development are reviewed.
RECENT FINDINGSProbiotic use may reduce incident CDI in high-risk populations by as much as 50%, though prior clinical trials have yielded conflicting results. Combining probiotics with prebiotics improves growth and engraftment in the host. Bacillus clausii and Lactobacillus reuteri secrete compounds that directly inhibit C. difficile. Organisms that produce secondary bile acids, such as Clostridium scindens, enhance C. difficile colonization resistance. Nontoxigenic C. difficile, which provides nutritional niche competition, may prevent CDI. Refinements to fecal microbiota transplantation (FMT) blur the line between probiotics and FMT. These include a quality-controlled stool product (RBX2660), purified Firmicutes spores (SER-109) and sterile fecal filtrate. Bacteriophages may treat CDI but have unknown safety and efficacy in humans.
SUMMARYThere have been a number of advances in probiotics and our understanding of their role in prevention of CDI, but a number of important safety and efficacy questions remain. An improved understanding of the native microbiota structure and function will allow for continued development of rationally designed probiotic therapy to provide enhanced protection against CDI.
Multidrug-resistant gram-negative bacteria (MDR-GNB) pose one of the greatest challenges to health care today because of their propensity for human-to-human transmission and lack of therapeutic ...options. Containing the spread of MDR-GNB is challenging, and the application of multifaceted infection control bundles during an evolving outbreak makes it difficult to measure the relative impact of each measure. This article will review the utility of various infection control measures in containing the spread of various MDR-GNB and will provide the supporting evidence for these interventions.
Commentary on An Elderly Man with Dementia Mills, John R
Clinical chemistry (Baltimore, Md.),
2020-Mar-01, 2020-03-01, 20200301, Letnik:
66, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Using Bayes Theorem the authors illustrate that efforts to reduce false-positive results should focus on selecting patients with high pre-test probability. Predictive models have been developed that ...can aid clinicians in determining whether a patient is likely to have a clinically relevant neural-specific antibody based on clinical features, standard laboratory tests, and MRI findings (2). Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 4 requirements: (a) significant contributions to the conception and design, acquisition ofdata, or analysis andinterpretation ofdata; (b) drafting or revising the article for intellectual content; (c) final approval of the published article; and (d) agreement to be accountable for all aspects of the article thus ensuring that questions related to the accuracy or integrity of any part of the article are appropriately investigated and resolved.
Targeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation ...that controls ribosome recruitment flux is eukaryotic initiation factor (eIF) 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition.
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•CRISPR/Cas9 gene editing is a powerful approach for in vivo drug-target validation•Rocaglates interact with eIF4A1 in vitro and in vivo•Anti-neoplastic activity of rocaglates is a consequence of eIF4A1 inhibition
Rocaglates are anti-neoplastic agents that are thought to inhibit the RNA helicase eIF4A, although alternative targets have also been proposed. Using a series of biochemical assays and CRISPR/Cas9 genome editing, Chu et al. provide genetic evidence that the anti-neoplastic activities of rocaglates are a consequence of eIF4A1 inhibition.
This study characterizes the frequency and sex ratio of positive test results for myelin oligodendrocyte glycoprotein–IgG and aquaporin-4–IgG in adult and pediatric patient populations in a single ...center.
Presbycusis Gates, George A; Mills, John H
The Lancet (British edition),
09/2005, Letnik:
366, Številka:
9491
Journal Article
Recenzirano
The inevitable deterioration in hearing ability that occurs with age—presbycusis—is a multifactorial process that can vary in severity from mild to substantial. Left untreated, presbycusis of a ...moderate or greater degree affects communication and can contribute to isolation, depression, and, possibly, dementia. These psychological effects are largely reversible with rehabilitative treatment. Comprehensive rehabilitation is widely available but underused because, in part, of social attitudes that undervalue hearing, in addition to the cost and stigma of hearing aids. Remediation of presbycusis is an important contributor to quality of life in geriatric medicine and can include education about communication effectiveness, hearing aids, assistive listening devices, and cochlear implants for severe hearing loss. Primary care physicians should screen and refer their elderly patients for assessment and remediation. Where hearing aids no longer provide benefit, cochlear implantation is the treatment of choice with excellent results even in octogenarians.
Since their approval in 2014, immune checkpoint inhibitors (ICIs)2 have transformed cancer care. ...the Food and Drug Administration recently designated the bTMB assay as a "breakthrough device," ...prioritizing the test for review. ...the successes of tissue-based TMB may not be transferrable to bTMB.
IMPORTANCE: Myelin oligodendrocyte glycoprotein-IgG1–associated disorder (MOGAD) is a distinct central nervous system–demyelinating disease. Positive results on MOG-IgG1 testing by live cell-based ...assays can confirm a MOGAD diagnosis, but false-positive results may occur. OBJECTIVE: To determine the positive predictive value (PPV) of MOG-IgG1 testing in a tertiary referral center. DESIGN, SETTING, AND PARTICIPANTS: This diagnostic study was conducted over 2 years, from January 1, 2018, through December 31, 2019. Patients in the Mayo Clinic who were consecutively tested for MOG-IgG1 by live cell-based flow cytometry during their diagnostic workup were included. Patients without research authorization were excluded. MAIN OUTCOMES AND MEASURES: Medical records of patients who were tested were initially reviewed by 2 investigators blinded to MOG-IgG1 serostatus, and pretest probability was classified as high or low (suggestive of MOGAD or not). Testing of MOG-IgG1 used a live-cell fluorescence-activated cell-sorting assay; an IgG binding index value of 2.5 or more with an end titer of 1:20 or more was considered positive. Cases positive for MOG-IgG1 were independently designated by 2 neurologists as true-positive or false-positive results at last follow-up, based on current international recommendations on diagnosis or identification of alternative diagnoses; consensus was reached for cases in which disagreement existed. RESULTS: A total of 1617 patients were tested, and 357 were excluded. Among 1260 included patients tested over 2 years, the median (range) age at testing was 46 (0-98) years, and 792 patients were female (62.9%). A total of 92 of 1260 (7.3%) were positive for MOG-IgG1. Twenty-six results (28%) were designated as false positive by the 2 raters, with an overall agreement on 91 of 92 cases (99%) for true and false positivity. Alternative diagnoses included multiple sclerosis (n = 11), infarction (n = 3), B12 deficiency (n = 2), neoplasia (n = 2), genetically confirmed adrenomyeloneuropathy (n = 1), and other conditions (n = 7). The overall PPV (number of true-positive results/total positive results) was 72% (95% CI, 62%-80%) and titer dependent (PPVs: 1:1000, 100%; 1:100, 82%; 1:20-40, 51%). The median titer was higher with true-positive results (1:100 range, 1:20-1:10000) than false-positive results (1:40 range, 1:20-1:100; P < .001). The PPV was higher for children (94% 95% CI, 72%-99%) vs adults (67% 95% CI, 56%-77%) and patients with high pretest probability (85% 95% CI, 76%-92%) vs low pretest probability (12% 95% CI, 3%-34%). The specificity of MOG-IgG1 testing was 97.8%. CONCLUSIONS AND RELEVANCE: This study confirms MOG-IgG1 as a highly specific biomarker for MOGAD, but when using a cutoff of 1:20, it has a low PPV of 72%. Caution is advised in the interpretation of low titers among patients with atypical phenotypes, because ordering MOG-IgG1 in low pretest probability situations will increase the proportion of false-positive results.
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