Is Non-Steroidal Anti-Inflammatory Therapy Non-Inferior to Antibiotic Therapy in Uncomplicated Urinary Tract Infections: a Systematic Review.

BACKGROUND: Amid growing antimicrobial resistance, there is an increasing focus on antibiotic stewardship efforts to reduce inappropriate antibiotic prescribing. In this context, novel approaches for treating infections without antibiotics are being explored. One such strategy is the use of non-steroidal anti-inflammatory drugs (NSAIDs) for uncomplicated urinary tract infections (UTIs). Therefore, we conducted a systematic review of randomized controlled trials to evaluate the rates of symptom resolution and infectious complications in adult women with uncomplicated UTIs treated with antibiotics versus NSAIDs. METHODS: We systematically searched PubMed, CINHAL, Scopus, Web of Science Core Collection, EMBASE, and ClinicalTrials.gov from inception until January 13, 2020, for randomized controlled trials comparing NSAIDs with antibiotics for treatment of uncomplicated UTIs in adult women. Studies comparing symptom resolution between groups were eligible. Two authors screened all studies independently and in duplicate; data were abstracted using a standardized template. Risk of bias was assessed using the Cochrane Collaboration tool. RESULTS: Five randomized trials that included 1309 women with uncomplicated UTI met inclusion criteria. Three studies (1130 patients) favored antibiotic therapy in terms of symptom resolution. Two studies (179 patients) found no difference between NSAIDs and antibiotics in terms of symptom resolution. Three studies reported rates of pyelonephritis, two of which found higher rates in patients treated with NSAIDs versus antibiotics. Between two studies that reported this outcome (747 patients), patients randomized to NSAIDs received fewer antibiotic prescriptions compared with those in the antibiotics group. Three studies were at low risk of bias, one had an unclear risk of bias, and one was at high risk of bias. DISCUSSION: For the outcomes of symptom resolution and complications in adult women with UTI, evidence favors antibiotics over NSAIDs. PROSPERO: CRD42018114133.

Exercise-induced myocardial dysfunction detected by cardiopulmonary exercise testing is associated with increased risk of mortality in major oncological colorectal surgery.

BACKGROUND: Cardiopulmonary exercise testing (CPET) identifies high-risk patients before major surgery. In addition to using oxygen uptake and ventilatory efficiency to assess functional capacity, CPET can be used to identify underlying myocardial dysfunction through the assessment of the oxygen uptake to heart rate response (oxygen pulse response). We examined the relationship of oxygen pulse response, in combination with other CPET variables and known cardiac risk factors, with mortality after colorectal cancer surgery. METHODS: This work focused on a retrospective cohort study of patients who had CPET and underwent colorectal cancer surgery. The primary outcome was a composite of in-hospital and 30-day mortality. Ventilatory inefficiency (Ve/Vco2>34) and exercise-induced myocardial dysfunction (abnormal oxygen pulse response) were investigated for an association with mortality using bivariable analysis and multivariable Cox regression. RESULTS: A total of 1214 patients who underwent colorectal cancer surgery were included, and the primary outcome occurred in 26 patients (2.1%). Multivariable Cox regression showed abnormal oxygen pulse response was independently associated with the primary outcome (odds ratio [OR]=2.75; 95% confidence interval [CI], 1.17-6.47). Bivariable analysis showed that Ve/Vco2 >34 was associated with the primary outcome (OR=3.43; 95% CI, 1.47-8.01). Combining Ve/Vco2 >34 and abnormal oxygen pulse response conferred an increased risk for the primary outcome (OR=4.47; 95% CI, 1.62-12.34), compared with Ve/Vco2 >34 and normal oxygen pulse response. CONCLUSION: Ventilatory inefficiency and an abnormal oxygen pulse response were independently associated with short- (30-day) and long-term (2-yr) mortality. Oxygen pulse response may provide additional information when considering perioperative risk stratification.

Interventions to reduce aggressive care at end of life among patients with cancer: a systematic review.

Little is known about effective interventions to reduce aggressive end-of-life care in patients with cancer. We did a systematic review to assess what interventions are associated with reductions in aggressive end-of-life cancer care. We searched MEDLINE, CINAHL, Embase, Scopus, and PsychINFO for randomised control trials (RCTs), quasi-experimental, and observational studies published before Jan 19, 2018, which aimed to improve measures of aggressive end-of-life care for patients with cancer. We developed a taxonomy of interventions using the Systems Engineering Initiative for Patient Safety (SEIPS) model to summarise existing interventions that addressed aggressive care for patients with cancer. Of the 6451 studies identified by our search, five RCTs and 31 observational studies met the final inclusion criteria. Using the SEIPS framework, 16 subcategories of interventions were identified. With the exception of documentation of end-of-life discussions in the electronic medical record, no single intervention type or SEIPS domain led to consistent improvements in aggressive end-of-life care measures. The ability to discern the interventions' effectiveness was limited by inconsistent use of validated measures of aggressive care. Seven (23%) of 31 observational studies and no RCTs were at low risk of bias according to Cochrane's Risk of Bias tool. Evidence for improving aggressive end-of-life cancer care is limited by the absence of standardised measurements and poor study design. Policies and studies to address the gaps present in end-of-life care for cancer are necessary.

In situ synchrotron XRD analysis of the kinetics of spodumene phase transitions.

The phase transition by thermal activation of natural α-spodumene was followed by in situ synchrotron XRD in the temperature range 896 to 940 °C. We observed both ß- and γ-spodumene as primary products in approximately equal proportions. The rate of the α-spodumene inversion is first order and highly sensitive to temperature (apparent activation energy ∼800 kJ mol-1). The γ-spodumene product is itself metastable, forming ß-spodumene, with the total product mass fraction ratio fγ/fß decreasing as the conversion of α-spodumene continues. We found the relationship between the product yields and the degree of conversion of α-spodumene to be the same at all temperatures in the range studied. A model incorporating first order kinetics of the α- and γ-phase inversions with invariant rate constant ratio describes the results accurately. Theoretical phonon analysis of the three phases indicates that the γ phase contains crystallographic instabilities, whilst the α and ß phases do not.

Early Versus Delayed Feeding in Patients With Acute Pancreatitis: A Systematic Review.

BACKGROUND: Acute pancreatitis is among the most common and costly reasons for hospitalization in the United States. Bowel rest, pain control, and intravenous fluids are the cornerstones of treatment, but early feeding might also be beneficial. PURPOSE: To compare length of hospital stay, mortality, and readmission in adults hospitalized with pancreatitis who received early versus delayed feeding. DATA SOURCES: MEDLINE via Ovid, EMBASE, the Cochrane Library, CINAHL, and Web of Science through January 2017. STUDY SELECTION: Two authors independently reviewed and selected studies if they were randomized clinical trials, included adults hospitalized with acute pancreatitis, and compared early versus delayed feeding (≤48 vs. >48 hours after hospitalization). DATA EXTRACTION: Two investigators independently extracted study data and rated risk of bias using the Cochrane Collaboration tool. DATA SYNTHESIS: Eleven randomized trials (8 peer-reviewed publications, 3 abstract-only presentations) that included 948 patients were eligible. Seven trials (3 with low risk of bias) enrolled patients with mild to moderate pancreatitis. Four trials (1 with low risk of bias) included patients with predicted severe pancreatitis. Routes used for early feeding included oral (4 studies), nasogastric (2 studies), nasojejunal (4 studies), and oral or nasoenteric (1 study). Among patients with mild to moderate pancreatitis, early feeding was associated with reduced length of stay in 4 of 7 studies (including 2 of 3 with low risk of bias). Other outcomes were heterogeneous and variably reported, but no study showed an increase in adverse events with early feeding. Among patients with severe pancreatitis, limited evidence revealed no statistically significant difference in outcomes between early and delayed feeding. LIMITATION: Heterogeneity of feeding protocols and outcomes, scant data, and unclear or high risk of bias in several studies. CONCLUSION: Limited data suggest that early feeding in patients with acute pancreatitis does not seem to increase adverse events and, for patients with mild to moderate pancreatitis, may reduce length of hospital stay. PRIMARY FUNDING SOURCE: None. (PROSPERO: CRD42015016193).

Internet-Delivered Health Interventions That Work: Systematic Review of Meta-Analyses and Evaluation of Website Availability.

BACKGROUND: Due to easy access and low cost, Internet-delivered therapies offer an attractive alternative to improving health. Although numerous websites contain health-related information, finding evidence-based programs (as demonstrated through randomized controlled trials, RCTs) can be challenging. We sought to bridge the divide between the knowledge gained from RCTs and communication of the results by conducting a global systematic review and analyzing the availability of evidence-based Internet health programs. OBJECTIVES: The study aimed to (1) discover the range of health-related topics that are addressed through Internet-delivered interventions, (2) generate a list of current websites used in the trials which demonstrate a health benefit, and (3) identify gaps in the research that may have hindered dissemination. Our focus was on Internet-delivered self-guided health interventions that did not require real-time clinical support. METHODS: A systematic review of meta-analyses was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO Registration Number CRD42016041258). MEDLINE via Ovid, PsycINFO, Embase, Cochrane Database of Systematic Reviews, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) were searched. Inclusion criteria included (1) meta-analyses of RCTs, (2) at least one Internet-delivered intervention that measured a health-related outcome, and (3) use of at least one self-guided intervention. We excluded group-based therapies. There were no language restrictions. RESULTS: Of the 363 records identified through the search, 71 meta-analyses met inclusion criteria. Within the 71 meta-analyses, there were 1733 studies that contained 268 unique RCTs which tested self-help interventions. On review of the 268 studies, 21.3% (57/268) had functional websites. These included evidence-based Web programs on substance abuse (alcohol, tobacco, cannabis), mental health (depression, anxiety, post-traumatic stress disorder [PTSD], phobias, panic disorders, obsessive compulsive disorder [OCD]), and on diet and physical activity. There were also evidence-based programs on insomnia, chronic pain, cardiovascular risk, and childhood health problems. These programs tended to be intensive, requiring weeks to months of engagement by the user, often including interaction, personalized and normative feedback, and self-monitoring. English was the most common language, although some were available in Spanish, French, Portuguese, Dutch, German, Norwegian, Finnish, Swedish, and Mandarin. There were several interventions with numbers needed to treat of <5; these included painACTION, Mental Health Online for panic disorders, Deprexis, Triple P Online (TPOL), and U Can POOP Too. Hyperlinks of the sites have been listed. CONCLUSIONS: A wide range of evidence-based Internet programs are currently available for health-related behaviors, as well as disease prevention and treatment. However, the majority of Internet-delivered health interventions found to be efficacious in RCTs do not have websites for general use. Increased efforts to provide mechanisms to host "interventions that work" on the Web and to assist the public in locating these sites are necessary.

Bone marrow-derived and resident liver macrophages display unique transcriptomic signatures but similar biological functions.

BACKGROUND & AIMS: Kupffer cells (KCs), the resident tissue macrophages of the liver, play a crucial role in the clearance of pathogens and other particulate materials that reach the systemic circulation. Recent studies have identified KCs as a yolk sac-derived resident macrophage population that is replenished independently of monocytes in the steady state. Although it is now established that following local tissue injury, bone marrow derived monocytes may infiltrate the tissue and differentiate into macrophages, the extent to which newly differentiated macrophages functionally resemble the KCs they have replaced has not been extensively studied. METHODS: We studied the two populations of KCs using intravital microscopy, morphometric analysis and gene expression profiling. An ion homeostasis gene signature, including genes associated with scavenger receptor function and extracellular matrix deposition, allowed discrimination between these two KC sub-types. RESULTS: Bone marrow derived "KCs" accumulating as a result of genotoxic injury, resemble but are not identical to their yolk sac counterparts. Reflecting the differential expression of scavenger receptors, yolk sac-derived KCs were more effective at accumulating acetylated low density lipoprotein, whereas surprisingly, they were poorer than bone marrow-derived KCs when assessed for uptake of a range of bacterial pathogens. The two KC populations were almost indistinguishable in regard to i) response to lipopolysaccharide challenge, ii) phagocytosis of effete red blood cells and iii) their ability to contain infection and direct granuloma formation against Leishmania donovani, a KC-tropic intracellular parasite. CONCLUSIONS: Bone marrow-derived KCs differentiate locally to resemble yolk sac-derived KC in most but not all respects, with implications for models of infectious diseases, liver injury and bone marrow transplantation. In addition, the gene signature we describe adds to the tools available for distinguishing KC subpopulations based on their ontology. LAY SUMMARY: Liver macrophages play a major role in the control of infections in the liver and in the pathology associated with chronic liver diseases. It was recently shown that liver macrophages can have two different origins, however, the extent to which these populations are functionally distinct remains to be fully addressed. Our study demonstrates that whilst liver macrophages share many features in common, regardless of their origin, some subtle differences in function exist. DATA REPOSITORY: Gene expression data are available from the European Bioinformatics Institute ArrayExpress data repository (accession number E-MTAB-4954).

Marked serum procalcitonin level in response to isolated anaphylactic shock.

The objective of this study was to present a case report that highlights the limitation of serum procalcitonin levels greater than 10 ng/mL as being almost exclusively secondary to septic shock. Data source was a medical intensive care unit patient at the University of Louisville. Anaphylactic shock may cause elevations of serum procalcitonin to levels greater than 10 ng/mL.

IL-10-producing Th1 cells and disease progression are regulated by distinct CD11c⁺ cell populations during visceral leishmaniasis.

IL-10 is a critical regulatory cytokine involved in the pathogenesis of visceral leishmaniasis caused by Leishmania donovani and clinical and experimental data indicate that disease progression is associated with expanded numbers of CD4⁺ IFNγ⁺ T cells committed to IL-10 production. Here, combining conditional cell-specific depletion with adoptive transfer, we demonstrate that only conventional CD11c(hi) DCs that produce both IL-10 and IL-27 are capable of inducing IL-10-producing Th1 cells in vivo. In contrast, CD11c(hi) as well as CD11c(int/lo) cells isolated from infected mice were capable of reversing the host protective effect of diphtheria toxin-mediated CD11c⁺ cell depletion. This was reflected by increased splenomegaly, inhibition of NO production and increased parasite burden. Thus during chronic infection, multiple CD11c⁺ cell populations can actively suppress host resistance and enhance immunopathology, through mechanisms that do not necessarily involve IL-10-producing Th1 cells.

Control of the graphene-protein interface is required to preserve adsorbed protein function.

Graphene's suite of useful properties makes it of interest for use in biosensors. However, graphene interacts strongly with hydrophobic components of biomolecules, potentially altering their conformation and disrupting their biological activity. We have immobilized the protein Concanavalin A onto a self-assembled monolayer of multivalent tripodal molecules on single-layer graphene. We used a quartz crystal microbalance (QCM) to show that tripod-bound Concanavalin A retains its affinity for polysaccharides containing α-D-glucopyrannosyl groups as well as for the α-D-mannopyranosyl groups located on the cell wall of Bacillus subtilis. QCM measurements on unfunctionalized graphene indicate that adsorption of Concanavalin A onto graphene is accompanied by near-complete loss of these functions, suggesting that interactions with the graphene surface induce deleterious structural changes to the protein. Given that Concanavalin A's tertiary structure is thought to be relatively robust, these results suggest that other proteins might also be denatured upon adsorption onto graphene, such that the graphene-biomolecule interface must be considered carefully. Multivalent tripodal binding groups address this challenge by anchoring proteins without loss of function and without disrupting graphene's desirable electronic structure.

Quantification of the surface diffusion of tripodal binding motifs on graphene using scanning electrochemical microscopy.

The surface diffusion of a cobalt bis-terpyridine, Co(tpy)(2)-containing tripodal compound (1·2PF(6)), designed to noncovalently adsorb to graphene through three pyrene moieties, has been studied by scanning electrochemical microscopy (SECM) on single-layer graphene (SLG). An initial boundary approach was designed in which picoliter droplets (radii ~15-50 µm) of the tripodal compound were deposited on an SLG electrode, yielding microspots in which a monolayer of the tripodal molecules is initially confined. The time evolution of the electrochemical activity of these spots was detected at the aqueous phosphate buffer/SLG interface by SECM, in both generation/collection (G/C) and feedback modes. The tripodal compound microspots exhibit differential reactivity with respect to the underlying graphene substrate in two different electrochemical processes. For example, during the oxygen reduction reaction, adsorbed 1·2PF(6) tripodal molecules generate more H(2)O(2) than the bare graphene surface. This product was detected with spatial and temporal resolution using the SECM tip. The tripodal compound also mediates the oxidation of a Fe(II) species, generated at the SECM tip, under conditions in which SLG shows slow interfacial charge transfer. In each case, SECM images, obtained at increasing times, show a gradual decrease in the electrochemical response due to radial diffusion of the adsorbed molecules outward from the microspots onto the unfunctionalized areas of the SLG surface. This response was fit to a simple surface diffusion model, which yielded excellent agreement between the two experiments for the effective diffusion coefficients: D(eff) = 1.6 (±0.9) × 10(-9) cm(2)/s and D(eff) = 1.5 (±0.6) × 10(-9) cm(2)/s for G/C and feedback modes, respectively. Control experiments ruled out alternative explanations for the observed behavior, such as deactivation of the Co(II/III) species or of the SLG, and verified that the molecules do not diffuse when confined to obstructed areas. The noncovalent nature of the surface functionalization, together with the surface reactivity and mobility of these molecules, provides a means to couple the superior electronic properties of graphene to compounds with enhanced electrochemical performance, a key step toward developing dynamic electrode surfaces for sensing, electrocatalysis, and electronic applications.

Multivalent binding motifs for the noncovalent functionalization of graphene.

Single-layer graphene is a newly available conductive material ideally suited for forming well-defined interfaces with electroactive compounds. Aromatic moieties typically interact with the graphene surface to maximize van der Waals interactions, predisposing most compounds to lie flat on its basal plane. Here we describe a tripodal motif that binds multivalently to graphene through three pyrene moieties and projects easily varied functionality away from the surface. The thermodynamic and kinetic binding parameters of a tripod bearing a redox-active Co(II) bis-terpyridyl complex were investigated electrochemically. The complex binds strongly to graphene and forms monolayers with a molecular footprint of 2.3 nm(2) and a ΔG(ads) = -38.8 ± 0.2 kJ mol(-1). Its monolayers are stable in fresh electrolyte for more than 12 h and desorb from graphene 1000 times more slowly than model compounds bearing a single aromatic binding group. Differences in the heterogeneous rate constants of electron transfer between the two compounds suggest that the tripod projects its redox couple away from the graphene surface.

Primary and Specialty Outpatient Visits for Older Women With Urinary Incontinence: A Comparison of Nurses to the General Population.

OBJECTIVE: We evaluated patterns of outpatient visits seen for urinary incontinence (UI) among women 65 years or older in the Nurses' Health Study and the general Medicare population. We were interested in understanding whether nurses, with high health literacy, may receive more care for UI than the general population. METHODS: Medicare Fee for Service claims data for women aged 66-91 years were compared for Nurses' Health Study participants (n = 3,213) and a propensity-matched sample from general Medicare Fee for Service beneficiaries (n = 3,213) with 1 or more outpatient evaluation and management visits for UI in 2012. We examined the mean number of outpatient visits for UI and the type of provider seen, using t tests and χ2 tests. Providers were categorized as specialist and nonspecialist providers using taxonomy codes. RESULTS: The percentage of women 65 years or older who had an outpatient visits for UI over 12 months was 6.4% in the Nurses' Health Study cohort and 5.4% in the general population. The mean number of office visits for UI in 2012 was similar between nurses and the matched general population (mean = 1.8 vs 1.8; P = 0.3). A small percentage of women saw both nonspecialists and specialists for UI (9.3% in the Nurses' Health Study and 10.0% in the Center for Medicare Services cohorts). CONCLUSIONS: We found that less than 7% of older women had outpatient evaluation of UI symptoms during a 12-month period, despite UI being very common in this age group. This was similar in nurses and the general population, suggesting that even high health care literacy does not increase UI care seeking.

High versus low mean arterial pressures in hepatorenal syndrome: A randomized controlled pilot trial.

There is controversy regarding the mean arterial pressure (MAP) goals that should be targeted in the treatment of hepatorenal syndrome (HRS.) We conducted a study to assess different MAP targets in HRS in the intensive care unit (ICU). MATERIALS AND METHODS: This is a prospective randomized controlled pilot trial. ICU patients had target mean arterial pressure (MAP) ≥ 85 mmHg (control arm) or 65-70 mmHg (study arm). Urine output and serum creatinine were trended and recorded. RESULTS: A total of 18 patients were enrolled. The day four urine output in the high and low MAP group was 1194 (SD = 1249) mL/24 h and 920 (SD = 812) mL/24 h, respectively. The difference in day four - day one urine output was -689 (SD = 1684) mL/24 h and 272 (SD = 582) mL/24 h for the high and low MAP groups. The difference in serum creatinine at day four - day one was -0.54 (SD = 0.63) mg/dL and - 0.77 (SD = 1.14) mg/dL in the high and low MAP groups, respectively. CONCLUSION: In this study, we failed to prove non-inferiority between a low and high target MAP in patients with HRS. TRIAL REGISTRATION: This trial was registered with and approved by the University of Louisville Internal Review Board and hospital research review committees (IRB # 14.1190). The trial was registered with ClinicalTrials.gov (ID # NCT02789150). The IRB committee roster 7/21/2014-2/26/2015 is registered with IORG (IORG # IORG0000147; OMB # 0990-0279) and is available at http://louisville.edu/research/humansubjects/about-the-irb/rosters/RosterEffective20140721thru20150226.pdf.

Catheter management after benign transurethral prostate surgery: RAND/UCLA Appropriateness Criteria.

OBJECTIVES: To formally assess the appropriateness of different timings of urethral catheter removal after transurethral prostate resection or ablation. Although urethral catheter placement is routine after this common treatment for benign prostatic hyperplasia (BPH), no guidelines inform duration of catheter use. STUDY DESIGN: RAND/UCLA Appropriateness Methodology. METHODS: Using a standardized, multiround rating process (ie, the RAND/UCLA Appropriateness Methodology), an 11-member multidisciplinary panel reviewed a literature summary and rated clinical scenarios for urethral catheter duration after transurethral prostate surgery for BPH as appropriate (ie, benefits outweigh risks), inappropriate, or of uncertain appropriateness. We examined appropriateness across 4 clinical scenarios (no preexisting catheter, preexisting catheter [including intermittent], difficult catheter placement, significant perforation) and 5 durations (postoperative day [POD] 0, 1, 2, 3-6, or ≥7). RESULTS: Urethral catheter removal and first trial of void on POD 1 was rated appropriate for all scenarios except clinically significant perforations. In this case, waiting until POD 3 was deemed the earliest appropriate timing. Waiting 3 or more days to remove the catheter for patients with or without preexisting catheter needs, or for those with difficult catheter placement in the operating room, was rated as inappropriate. CONCLUSIONS: We defined clinically relevant guidance statements for the appropriateness of urethral catheter duration after transurethral prostate surgery. Given the lack of guidelines and this robust expert panel approach, these ratings may help clinicians and healthcare systems improve the consistency and quality of care for patients undergoing transurethral surgery for BPH.

Michigan Appropriate Perioperative (MAP) criteria for urinary catheter use in common general and orthopaedic surgeries: results obtained using the RAND/UCLA Appropriateness Method.

BACKGROUND: Indwelling urinary catheters are commonly used for patients undergoing general and orthopaedic surgery. Despite infectious and non-infectious harms of urinary catheters, there is limited guidance available to surgery teams regarding appropriate perioperative catheter use. OBJECTIVE: Using the RAND Corporation/University of California Los Angeles (RAND/UCLA) Appropriateness Method, we assessed the appropriateness of indwelling urinary catheter placement and different timings of catheter removal for routine general and orthopaedic surgery procedures. METHODS: Two multidisciplinary panels consisting of 13 and 11 members (physicians and nurses) for general and orthopaedic surgery, respectively, reviewed the available literature regarding the impact of different perioperative catheter use strategies. Using a standardised, multiround rating process, the panels independently rated clinical scenarios (91 general surgery, 36 orthopaedic surgery) for urinary catheter placement and postoperative duration of use as appropriate (ie, benefits outweigh risks), inappropriate or of uncertain appropriateness. RESULTS: Appropriateness of catheter use varied by procedure, accounting for procedure-specific risks as well as expected procedure time and intravenous fluids. Procedural appropriateness ratings for catheters were summarised for clinical use into three groups: (1) can perform surgery without catheter; (2) use intraoperatively only, ideally remove before leaving the operating room; and (3) use intraoperatively and keep catheter until postoperative days 1-4. Specific recommendations were provided by procedure, with postoperative day 1 being appropriate for catheter removal for first voiding trial for many procedures. CONCLUSION: We defined the appropriateness of indwelling urinary catheter use during and after common general and orthopaedic surgical procedures. These ratings may help reduce catheter-associated complications for patients undergoing these procedures.

How often are health care personnel hands colonized with multidrug- resistant organisms? A systematic review and meta-analysis.

BACKGROUND: Hands of health care personnel (HCP) can transmit multidrug-resistant organisms (MDROs), resulting in infections. Our aim was to determine MDRO prevalence on HCP hands in adult acute care and nursing facility settings. METHODS: A systematic search of PubMed/MEDLINE, Web of Science, CINAHL, Embase, and Cochrane CENTRAL was performed. Studies were included if they reported microbiologic culture results following HCP hands sampling; included prevalent MDROs, such as methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus, Clostridium difficile, Acinetobacter baumannii, or Pseudomonas aeruginosa, and were conducted in acute care or nursing facility settings. RESULTS: Fifty-nine articles comprising 6,840 hand cultures were included. Pooled prevalence for MRSA, P aeruginosa, A baumannii, and vancomycin-resistant Enterococcus were 4.26%, 4.59%, 6.18%, and 9.03%, respectively. Substantial heterogeneity in rates of pathogen isolation were observed across studies (I2 = 81%-95%). Only 4 of 59 studies sampled for C difficile, with 2 of 4 finding no growth. Subgroup analysis of MRSA revealed the highest HCP hand contamination rates in North America (8.28%). Sample collection methods used were comparable for MRSA isolation (4%-7%) except for agar direct contact (1.55%). CONCLUSIONS: Prevalence of common MDROs on HCP hands vary by pathogen, care setting, culture acquisition method, study design, and geography. When obtained at an institutional level, these prevalence data can be utilized to enhance knowledge, practice, and research to prevent health care-associated infections.

Repression of prostaglandin dehydrogenase by epidermal growth factor and snail increases prostaglandin E2 and promotes cancer progression.

Prostaglandin E(2) (PGE(2)), a proinflammatory bioactive lipid, promotes cancer progression by modulating proliferation, apoptosis, and angiogenesis. PGE(2) is a downstream product of cyclooxygenase (COX) and is biochemically inactivated by prostaglandin dehydrogenase (PGDH). In the present study, we investigated the mechanisms by which PGDH is down-regulated in cancer. We show that epidermal growth factor (EGF) represses PGDH expression in colorectal cancer cells. EGF receptor (EGFR) signaling induces Snail, which binds conserved E-box elements in the PGDH promoter to repress transcription. Induction of PGE(2) catabolism through inhibition of EGFR signaling blocks cancer growth in vivo. In human colon cancers, elevated Snail expression correlates well with down-regulation of PGDH. These data indicate that PGDH may serve a tumor suppressor function in colorectal cancer and provide a possible COX-2-independent way to target PGE(2) to inhibit cancer progression.

Oncogenic function of a novel WD-domain protein, STRAP, in human carcinogenesis.

The development and progression of malignancies is a complex multistage process that involves the contribution of a number of genes giving growth advantage to cells when transformed. The role of transforming growth factor-beta (TGF-beta) in carcinogenesis is complex with tumor-suppressor or prooncogenic activities depending on the cell type and the stage of the disease. We have previously reported the identification of a novel WD-domain protein, STRAP, that associates with both TGF-beta receptors and that synergizes with the inhibitory Smad, Smad7, in the negative regulation of TGF-beta-induced transcription. Here, we show that STRAP is ubiquitously expressed and is localized in both cytoplasm and nucleus. STRAP is up-regulated in 60% colon and in 78% lung carcinomas. Stable expression of STRAP results in activation of mitogen-activated protein kinase/extracellular signal-regulated kinase pathway and in down-regulation of the cyclin-dependent kinase inhibitor p21(Cip1), which results in retinoblastoma protein hyperphosphorylation. In addition, we have observed that Smad2/3 phosphorylation, TGF-beta-mediated transcription, and growth inhibition are induced in STRAP-knockout mouse embryonic fibroblasts compared with wild-type cells. Ectopic expression of STRAP in A549 lung adenocarcinoma cell line inhibits TGF-beta-induced growth inhibition and enhances anchorage-independent growth of these cells. Moreover, overexpression of STRAP increases tumorigenicity in athymic nude mice. Knockdown of endogenous STRAP by small interfering RNA increases TGF-beta signaling, reduces ERK activity, increases p21(Cip1) expression, and decreases tumorigenicity. Taken together, these results suggest that up-regulation of STRAP in human cancers may provide growth advantage to tumor cells via TGF-beta-dependent and TGF-beta-independent mechanisms, thus demonstrating the oncogenic function of STRAP.