The effect of short-course antibiotics on the resistance profile of colonizing gut bacteria in the ICU: a prospective cohort study.

BACKGROUND: The need for early antibiotics in the intensive care unit (ICU) is often balanced against the goal of antibiotic stewardship. Long-course antibiotics increase the burden of antimicrobial resistance within colonizing gut bacteria, but the dynamics of this process are not fully understood. We sought to determine how short-course antibiotics affect the antimicrobial resistance phenotype and genotype of colonizing gut bacteria in the ICU by performing a prospective cohort study with assessments of resistance at ICU admission and exactly 72 h later. METHODS: Deep rectal swabs were performed on 48 adults at the time of ICU admission and exactly 72 h later, including patients who did and did not receive antibiotics. To determine resistance phenotype, rectal swabs were cultured for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). In addition, Gram-negative bacterial isolates were cultured against relevant antibiotics. To determine resistance genotype, quantitative PCR (qPCR) was performed from rectal swabs for 87 established resistance genes. Within-individual changes in antimicrobial resistance were calculated based on culture and qPCR results and correlated with exposure to relevant antibiotics (e.g., did ß-lactam antibiotic exposure associate with a detectable change in ß-lactam resistance over this 72-h period?). RESULTS: Of 48 ICU patients, 41 (85%) received antibiotics. Overall, there was no increase in the antimicrobial resistance profile of colonizing gut bacteria during the 72-h study period. There was also no increase in antimicrobial resistance after stratification by receipt of antibiotics (i.e., no detectable increase in ß-lactam, vancomycin, or macrolide resistance regardless of whether patients received those same antibiotics). This was true for both culture and PCR. Antimicrobial resistance pattern at ICU admission strongly predicted resistance pattern after 72 h. CONCLUSIONS: Short-course ICU antibiotics made little detectable difference in the antimicrobial resistance pattern of colonizing gut bacteria over 72 h in the ICU. This provides an improved understanding of the dynamics of antimicrobial resistance in the ICU and some reassurance that short-course antibiotics may not adversely impact the stewardship goal of reducing antimicrobial resistance.

Uroplakin 1b is critical in urinary tract development and urothelial differentiation and homeostasis.

Proper development and maintenance of urothelium is critical to its function. Uroplakins are expressed in developing and mature urothelium where they establish plaques associated with the permeability barrier. Their precise functional role in development and disease is unknown. Here, we disrupted Upk1b in vivo where its loss resulted in urothelial plaque disruption in the bladder and kidney. Upk1b(RFP/RFP) bladder urothelium appeared dysplastic with expansion of the progenitor cell markers, Krt14 and Krt5, increased Shh expression, and loss of terminal differentiation markers Krt20 and uroplakins. Upk1b(RFP/RFP) renal urothelium became stratified with altered cellular composition. Upk1b(RFP/RFP) mice developed age-dependent progressive hydronephrosis. Interestingly, 16% of Upk1b(RFP/RFP) mice possessed unilateral duplex kidneys. Our study expands the role of uroplakins, mechanistically links plaque formation to urinary tract development and function, and provides a tantalizing connection between congenital anomalies of the kidney and urinary tract along with functional deficits observed in a variety of urinary tract diseases. Thus, kidney and bladder urothelium are regionally distinct and remain highly plastic, capable of expansion through tissue-specific progenitor populations. Furthermore, Upk1b plays a previously unknown role in early kidney development representing a novel genetic target for congenital anomalies of the kidney and urinary tract.

Systematic review: radiomics for the diagnosis and prognosis of hepatocellular carcinoma.

BACKGROUND: Advances in imaging technology have the potential to transform the early diagnosis and treatment of hepatocellular carcinoma (HCC) through quantitative image analysis. Computational "radiomic" techniques extract biomarker information from images which can be used to improve diagnosis and predict tumour biology. AIMS: To perform a systematic review on radiomic features in HCC diagnosis and prognosis, with a focus on reporting metrics and methodologic standardisation. METHODS: We performed a systematic review of all full-text articles published from inception through December 1, 2019. Standardised data extraction and quality assessment metrics were applied to all studies. RESULTS: A total of 54 studies were included for analysis. Radiomic features demonstrated good discriminatory performance to differentiate HCC from other solid lesions (c-statistics 0.66-0.95), and to predict microvascular invasion (c-statistic 0.76-0.92), early recurrence after hepatectomy (c-statistics 0.71-0.86), and prognosis after locoregional or systemic therapies (c-statistics 0.74-0.81). Common stratifying features for diagnostic and prognostic radiomic tools included analyses of imaging skewness, analysis of the peritumoural region, and feature extraction from the arterial imaging phase. The overall quality of the included studies was low, with common deficiencies in both internal and external validation, standardised imaging segmentation, and lack of comparison to a gold standard. CONCLUSIONS: Quantitative image analysis demonstrates promise as a non-invasive biomarker to improve HCC diagnosis and management. However, standardisation of protocols and outcome measurement, sharing of algorithms and analytic methods, and external validation are necessary prior to widespread application of radiomics to HCC diagnosis and prognosis in clinical practice.

Gut colonization with vancomycin-resistant Enterococcus and risk for subsequent enteric infection.

BACKGROUND: Gut colonization with vancomycin-resistant Enterococcus (VRE) is associated with poor outcomes. This study evaluated the impact of VRE colonization on subsequent acquisition of enteric pathogens. METHODS: We performed a retrospective cohort study of adults admitted to an ICU from 2012 to 2017 who were screened for VRE colonization and subsequently underwent stool testing with a gastrointestinal pathogen PCR panel (GI PCR) with or without PCR testing for Clostridium difficile. Our primary outcome was the presence of any enteric pathogen. Cox proportional hazards modeling was used to adjust for factors associated with enteric infection. RESULTS: Of 761 patients who underwent VRE screening and subsequent GI PCR, 131 (17%) were colonized with VRE. Patients with VRE colonization were less likely to test positive on GI PCR compared to patients without VRE (9.2% vs 18%, p = 0.01); specifically for E. coli species (p = 0.03) and viral (p = 0.04) enteric infections. In 716 patients who underwent C. difficile testing, there was a trend towards more C. difficile infections in patients colonized with VRE (15% vs 10%, p = 0.11). On multivariable analysis, patients with VRE had a decreased risk of a positive GI PCR (aHR 0.47, 95% CI 0.25-0.88, p = 0.02) but not C. difficile infection, effects which persisted during 5 years of follow-up. Among positive tests, there was a greater proportion of C. difficile with VRE (57% vs 28%, p < 0.01). CONCLUSIONS: VRE colonization was associated with a decreased risk of subsequent non-C. difficile enteric infection. VRE domination of the gut microbiome may protect against acquisition of common enteric pathogens.

Diffusion and Use of Tethered Personal Health Records in Primary Care.

BACKGROUND: Personal health records (PHRs) enable patients to access their healthcare information in a secure environment, increasing patient engagement in medical care. PHRs can be tethered to a patient's electronic health record (EHR). Tethered PHRs, also known as patient portals, allow patients to access relevant medical information from their provider. Despite recent policy efforts to promote the use of health information technology and increased availability of PHRs in the clinical setting, PHR adoption rates remain relatively low overall. This article examines physician characteristics of high vs. low PHR adopters. OBJECTIVE: The objectives of this study were to (1) examine PHR use patterns in the primary care setting, (2) identify physician characteristics affecting PHR adoption, and (3) explore physician perspectives encouraging and deterring use. METHODS: Information technology records provided data on primary care patient portal use at a large Midwestern academic medical center. Electronic surveys were administered to affiliated primary care physicians to measure their perceived use of patient portals. A focus group consisting of physician providers who completed the survey was used to further elucidate the trends and perceived utilization of the patient portal in the clinical setting. RESULTS: While they expended significant time communicating with patients using the portal, physicians generally overestimated the time spent per week on the system. Physicians who had been in practice longer estimated a higher average time spent on the system when compared to newer physicians. Patient portal activation rates and use decreased with increased years in practice. During the focus groups, physicians voiced motivation to use patient portals because they perceived improved patient communication and satisfaction with use. However, continued lack of reimbursement for time spent in portal communication was reported as a major barrier to providers' engagement with this technology. DISCUSSION: Physician endorsement and engagement is critical to achieve widespread adoption of PHRs. Such endorsement can be obtained through (1) providing rewards from health system employers for high use of PHRs, (2) providing financial reimbursement for time spent electronically communicating with patients via the PHR from federal initiatives incentivizing meaningful use of health information technology, (3) building robust support staff assistance for PHR communication into primary care workflows, and (4) integrating more PHR-specific education into providers' EHR training.