Does active hepatitis C virus infection increase the risk for infection due to Staphylococcus aureus?

Infections with Staphylococcus aureus may be more frequent in subjects with active hepatitis C virus (HCV) infection. In this retrospective dual-cohort study, we sought to determine whether persons with active HCV infection (positive HCV antibody, detectable blood HCV RNA) were at greater risk of S. aureus infection than those with spontaneously resolved HCV infection (positive HCV antibody, negative blood HCV RNA). Based on prestudy power calculation, we included 231 subjects with active HCV and 116 subjects with resolved HCV infection. The two groups were well matched at baseline, except that subjects with active HCV had a higher mean Charlson's comorbidity index (2.2 vs. 1.3; p < 0.0001). Cohorts were followed for a mean of 3.67 years. Thirty-one of the 231 (13%) subjects with active HCV infection developed ≥1 S. aureus infection(s) as compared to 4/116 (3.4%) subjects with resolved HCV (p = 0.004), with a trend towards more recurrent S. aureus infections in subjects with active HCV infection. The S. aureus infections were mostly serious, necessitating hospitalization and intravenous antibiotics. In the logistic regression, factors that independently predicted S. aureus infection were active HCV and Charlson's comorbidity index. Our regression models confirmed that the enhanced susceptibility to S. aureus infections was related to active HCV infection and not attributable solely to the increased number of comorbidities [adjusted odds ratio (OR) = 3.3, 95% confidence interval (CI) 1.1-9.8; p = 0.03]. This study shows that subjects with active HCV infection have a significantly higher incidence of serious S. aureus infections than those with spontaneously resolved HCV, even after adjustment for comorbidities.

Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer.

BACKGROUND: Pain is associated with shorter survival in non-small cell lung cancer (NSCLC). Lung cancer cells express opioid receptors. Opioids promote angiogenesis, tumour growth, and metastases, and shorten survival in animal models. METHODS: We examined retrospectively if long-term opioid requirement, independently of chronic pain, is associated with reduced survival in 209 patients with stage IIIB/IV NSCLC. Opioid doses were converted to average oral morphine equivalents (OME). Patients were stratified by proportion of time they reported severe pain, and required <5 or ≥5 mg day-1 OME. Effects of pain, opioid requirement, and known prognostic variables on overall survival were analysed. RESULTS: Severe pain before chemotherapy initiation was associated with shorter survival (hazards ratio 1.39, 95% confidence interval, 1.02-1.87, P=0.035). The magnitude of pain and opioid requirement during first 90 days of chemotherapy were predictive of shorter survival: patients with no/mild pain and requiring <5 mg day-1 OME had 12 months longer median survival compared with those requiring more opioids, experiencing more pain, or both (18 compared with 4.2-7.7 months, P≤0.002). Survival differences (16 compared with 5.5-7.8 months, P<0.001) were similar when chronic pain and opioid requirement were assessed until death or last follow-up. In multivariable models, opioid requirement and chronic pain remained independent predictors of survival, after adjustment for age, stage, and performance status. CONCLUSIONS: The severity of chronic cancer-related pain or greater opioid requirement is associated with shorter survival in advanced NSCLC, independently of known prognostic factors. While pain adversely influences prognosis, controlling it with opioids does not improve survival. Prospective studies should determine if pain control using equi-analgesic opioid-sparing approaches can improve outcomes.

Association of stressful life events with accelerated bone loss in older men: the osteoporotic fractures in men (MrOS) study.

UNLABELLED: Prior studies suggest an association between stressful life events and fractures that may be mediated by BMD. In the current study, risk of accelerated hip BMD loss was higher in older men with any type of stressful life event and increased with the number of types of stressful life events. INTRODUCTION: Prior studies suggest that stressful life events may increase adverse health outcomes, including falls and possibly fractures. The current study builds on these findings and examines whether stressful life events are associated with increased bone loss. METHODS: Four thousand three hundred eighty-eight men aged ≥65 years in the Osteoporotic Fractures in Men study completed total hip bone mineral density (BMD) measures at baseline and visit 2, approximately 4.6 years later, and self-reported stressful life events data mid-way between baseline and visit 2, and at visit 2. We used linear regression to model the association of stressful life events with concurrent annualized total hip BMD loss, and log binomial regression or Poisson regression to model risk of concurrent accelerated BMD loss (>1 SD more than mean annualized change). RESULTS: Men (75.3 %) reported ≥1 type of stressful life event, including 43.3 % with ≥2 types of stressful life events. Mean annualized BMD loss was -0.36 % (SD 0.88), and 13.9 % of men were categorized with accelerated BMD loss (about 5.7 % or more total loss). Rate of annualized BMD loss increased with the number of types of stressful life events after adjustment for age (p < 0.001), but not after multivariable adjustment (p = 0.07). Multivariable-adjusted risk of accelerated BMD loss increased with the number of types of stressful life events (RR, 1.10 [95 % confidence interval (CI), 1.04-1.16]) per increase of one type of stressful life event). Fracture risk was not significantly different between stressful life event-accelerated bone loss subgroups (p = 0.08). CONCLUSIONS: In these older men, stressful life events were associated with a small, dose-related increase in risk of concurrent accelerated hip bone loss. Low frequency of fractures limited assessment of whether rapid bone loss mediates any association of stressful life events with incident fractures. Future studies are needed to confirm these findings and to investigate the mechanism that may underlie this association.

Spontaneous physical activity protects against fat mass gain.

OBJECTIVE: It is unclear whether elevated spontaneous physical activity (SPA, very low-intensity physical activity) positively influences body composition long term. We determined whether SPA and caloric intake were differentially related to the growth curve trajectories of body weight, fat mass (FM) and fat-free mass (FFM) between obesity resistant and Sprague-Dawley rats at specific age intervals. DESIGN AND SUBJECTS: Body composition, SPA and caloric intake were measured in selectively-bred obesity-resistant and out-bred Sprague-Dawley rats from 1 to 18 months. Data from development throughout maturation were analyzed by longitudinal growth curve modeling to determine the rate and acceleration of body weight, FM- and FFM-gain. RESULTS: Obesity-resistant rats had a lower rate of FM gain overall, a lower acceleration in body weight early in life, significantly greater SPA and lower cumulative caloric intake. Greater SPA in obesity-resistant rats was significantly associated with a lower rate of FM gain overall and lower acceleration in body weight early in life. Obesity resistant rats lost less FFM compared with Sprague-Dawley rats despite that obesity-resistant rats had a lower acceleration in FFM gain early in life. Obesity-resistant rats gained less FM and more FFM per gram body weight and were less energy efficient than Sprague-Dawley rats. Caloric intake was significantly and positively related to body weight, FM and FFM gain in both groups. Circadian patterns of caloric intake were group and age-dependent. Our data demonstrate that elevated and sustained SPA during development and over the lifespan are related to the reduced the rate of FM gain and may preserve FFM. CONCLUSION: These data support the idea that SPA level is a reproducible marker that reliably predicts propensity for obesity in rats, and that elevated levels of SPA maintained during the lifespan promote a lean phenotype.

Effects of butorphanol on feeding and neuropeptide Y in the rat.

Butorphanol ([BT] an opioid receptor agonist/antagonist) is different from other opioid agonists in that a single dose of BT can elicit up to 12 g of chow intake in a satiated rat whereas most opioid agonists induce a mild feeding response (2-3 g). Here, we first examined whether the effectiveness of BT to elicit feeding was affected by dose, method of infusion and possible tachyphylaxis following administration. Secondly, we examined whether BT administration influenced hypothalamic NPY gene expression and peptide levels. A single dose administration of BT (4 mg/kg) significantly increased food intake at 2, 3 and 6 h after administration. However following repeated injections of BT at 4 mg/kg, the cumulative long-term intake of BT-treated rats did not differ from that of controls, indicating that the animals compensate for the increased feeding following BT injection by decreased feeding at a later time. An ascending dose schedule of repeated BT injections resulted in additional feeding. NPY gene expression in the ARC was influenced by how much food had been consumed, but not by BT. The amount of food consumed and the level of NPY mRNA were inversely correlated. This is consistent with NPY's role in normal feeding. BT treatment did not affect either NPY or leptin RIA levels. We conclude that the feeding produced by BT is sensitive to dose and dosing paradigm. Further, its mechanism of action does not appear to be mediated by NPY or leptin pathways.

Blockade of nerve sprouting and neuroma formation markedly attenuates the development of late stage cancer pain.

For many patients, pain is the first sign of cancer and, while pain can be present at any time, the frequency and intensity of pain tend to increase with advancing stages of the disease. Thus, between 75 and 90% of patients with metastatic or advanced-stage cancer will experience significant cancer-induced pain. One major unanswered question is why cancer pain increases and frequently becomes more difficult to fully control with disease progression. To gain insight into this question we used a mouse model of bone cancer pain to demonstrate that as tumor growth progresses within bone, tropomyosin receptor kinase A (TrkA)-expressing sensory and sympathetic nerve fibers undergo profuse sprouting and form neuroma-like structures. To address what is driving the pathological nerve reorganization we administered an antibody to nerve growth factor (anti-NGF). Early sustained administration of anti-NGF, whose cognate receptor is TrkA, blocks the pathological sprouting of sensory and sympathetic nerve fibers, the formation of neuroma-like structures, and inhibits the development of cancer pain. These results suggest that cancer cells and their associated stromal cells release nerve growth factor (NGF), which induces a pathological remodeling of sensory and sympathetic nerve fibers. This pathological remodeling of the peripheral nervous system then participates in driving cancer pain. Similar to therapies that target the cancer itself, the data presented here suggest that, the earlier therapies blocking this pathological nerve remodeling are initiated, the more effective the control of cancer pain.

Evaluation of speech misattribution bias in schizophrenia.

BACKGROUND: The attribution of self-generated speech to others could explain the experience of verbal hallucinations. To test this hypothesis, we developed a task to simultaneously evaluate (A) operations of self-other distinction and (B) operations that have the same cognitive demands as in A apart from self-other distinction. By adjusting A to B, operations of self-other distinction were specifically evaluated. METHOD: Thirty-nine schizophrenia patients and 26 matched healthy controls were required to distinguish between self-generated, other-generated and non-generated (self or other) sentences. The sentences were in the first, second or third person and were read in a male or female voice in equal proportions. Mixed multi-level logistic regression models were used to investigate the effect of group, sentence source, pronoun and gender of the heard sentences on response accuracy. RESULTS: Patients differed from controls in the recognition of self-generated and other-generated sentences but not in general recognition ability. Pronoun was a significant predictor of response accuracy but without any significant interaction with group. Differences in the gender of heard sentences were not significant. Misattribution bias differentiated groups only in the self-other direction. CONCLUSIONS: These data support the theory that misattribution of self-generated speech to others could result in verbal hallucinations. The syntactic (pronoun) factor could impact self-other distinction in subtypes of verbal hallucinations that are phenomenologically defined whereas the acoustic factor (gender of heard speech) is unlikely to affect self-other distinction.

Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial.

OBJECTIVE: This phase 1 trial set out to examine the safety of a bacteriophage-based preparation for difficult-to-treat wounds. METHOD: The intention-to-treat sample comprised 42 patients with chronic venous leg ulcers (VLUs); 39 patients completed the trial. The ulcers were treated for 12 weeks with either a saline control or bacteriophages targeted against Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. Follow-up continued until week 24. RESULTS: No adverse events were attributed to the study product. No significant difference (p>0.05) was determined between the test and control groups for frequency of adverse events, rate of healing, or frequency of healing. CONCLUSION: This study found no safety concerns with the bacteriophage treatment. Efficacy of the preparation will need to be evaluated in a phase II efficacy study. DECLARATION OF INTEREST: One of the authors (AS) holds an equity interest in Intralytix. The other authors do not have any interest in commercial activities.

Capsaicin-sensitive sensory nerve fibers contribute to the generation and maintenance of skeletal fracture pain.

Although skeletal pain can have a marked impact on a patient's functional status and quality of life, relatively little is known about the specific populations of peripheral nerve fibers that drive non-malignant bone pain. In the present report, neonatal male Sprague-Dawley rats were treated with capsaicin or vehicle and femoral fracture was produced when the animals were young adults (15-16 weeks old). Capsaicin treatment, but not vehicle, resulted in a significant (>70%) depletion in the density of calcitonin-gene related peptide positive (CGRP(+)) sensory nerve fibers, but not 200 kDa neurofilament H positive (NF200(+)) sensory nerve fibers in the periosteum. The periosteum is a thin, cellular and fibrous tissue that tightly adheres to the outer surface of all but the articulated surface of bone and appears to play a pivotal role in driving fracture pain. In animals treated with capsaicin, but not vehicle, there was a 50% reduction in the severity, but no change in the time course, of fracture-induced skeletal pain-related behaviors as measured by spontaneous flinching, guarding and weight bearing. These results suggest that both capsaicin-sensitive (primarily CGRP(+) C-fibers) and capsaicin-insensitive (primarily NF200(+) A-delta fibers) sensory nerve fibers participate in driving skeletal fracture pain. Skeletal pain can be a significant impediment to functional recovery following trauma-induced fracture, osteoporosis-induced fracture and orthopedic surgery procedures such as knee and hip replacement. Understanding the specific populations of sensory nerve fibers that need to be targeted to inhibit the generation and maintenance of skeletal pain may allow the development of more specific mechanism-based therapies that can effectively attenuate acute and chronic skeletal pain.

Association of Parkinson's disease with accelerated bone loss, fractures and mortality in older men: the Osteoporotic Fractures in Men (MrOS) study.

UNLABELLED: Among community-dwelling older men, compared to those without Parkinson's disease (PD), over approximately 5 years, those with baseline PD had a significantly greater rate of annualized total hip bone loss (-1.1% vs. 0.4%), proportion of incident non-spine fractures (14.9% vs. 7.2%) and mortality (34.8% vs. 9.5%). INTRODUCTION: The objective of this study was to examine the association of Parkinson's disease (PD) with bone loss and fractures in older men. METHODS: This prospective cohort study analyzed data from 5,937 community dwelling men aged >or=65 years at six clinical centers of the Osteoporotic Fractures in Men (MrOS) Study. At baseline and visit two (mean interval 4.6 +/-0.4 SD years), community-diagnosed PD was ascertained by self-report and hip bone mineral density (BMD) was measured using dual energy x-ray absorptiometry (DXA). Incident fractures were self-reported. Fractures and deaths were centrally adjudicated. RESULTS: At baseline, 46 (0.8%) men had PD. Age-adjusted mean annualized total hip bone loss was greater in men with vs. those without PD (-1.08% vs. -0.36%, p < 0.001). 15.2% of men with PD and 7.2% of men without PD experienced an incident non-spine fracture (age-adjusted HR 2.4, 95%CI 1.1-5.0). 34.8% of men with PD and 9.5% of men without PD died during follow-up (age-adjusted HR 3.5, 95%CI 2.2-5.5). Associations of PD with bone loss, fractures and mortality were modestly altered by additional individual adjustment for possible confounders. CONCLUSIONS: In community-dwelling older men, PD was associated with increased bone loss, fractures and mortality. In addition to implementing fall prevention measures, clinicians should consider osteoporosis screening in older men with PD.

Weight loss during chronic, cervical vagus nerve stimulation in depressed patients with obesity: an observation.

Fourteen patients were treated over 2 years with cervical vagus nerve stimulation (VNS) for adjunctive therapy of severe, treatment-resistant depression. Here, we report the serendipitous observation that this treatment was associated with highly significant, gradual weight loss despite the patients' report of not dieting or exercising. The weight loss was proportional to the initial BMI, that is, the more severe the obesity, the greater the weight loss. Weight loss did not correlate with changes in mood symptoms. The vagus nerve carries visceral information to and from the brain; modulation of its activity may alter eating behavior. Chronic cervical VNS may merit controlled study for the treatment of severe obesity.

Elevated hypothalamic orexin signaling, sensitivity to orexin A, and spontaneous physical activity in obesity-resistant rats.

Selectively-bred obesity-resistant [diet resistant (DR)] rats weigh less than obesity-prone [diet-induced obese (DIO)] rats, despite comparable daily caloric intake, suggesting phenotypic energy expenditure differences. Human data suggest that obesity is maintained by reduced ambulatory or spontaneous physical activity (SPA). The neuropeptide orexin A robustly stimulates SPA. We hypothesized that DR rats have greater: 1) basal SPA, 2) orexin A-induced SPA, and 3) preproorexin, orexin 1 and 2 receptor (OX1R and OX2R) mRNA, compared with DIO rats. A group of age-matched out-bred Sprague-Dawley rats were used as additional controls for the behavioral studies. DIO, DR, and Sprague-Dawley rats with dorsal-rostral lateral hypothalamic (rLHa) cannulas were injected with orexin A (0, 31.25, 62.5, 125, 250, and 500 pmol/0.5 microl). SPA and food intake were measured for 2 h after injection. Preproorexin, OX1R and OX2R mRNA in the rLHa, and whole hypothalamus were measured by real-time RT-PCR. Orexin A significantly stimulated feeding in all rats. Orexin A-induced SPA was significantly greater in DR and Sprague-Dawley rats than in DIO rats. Two-mo-old DR rats had significantly greater rLHa OX1R and OX2R mRNA than DIO rats but comparable preproorexin levels. Eight-mo-old DR rats had elevated OX1R and OX2R mRNA compared with DIO rats, although this increase was significant for OX2R only at this age. Thus DR rats show elevated basal and orexin A-induced SPA associated with increased OX1R and OX2R gene expression, suggesting that differences in orexin A signaling through OX1R and OX2R may mediate DIO and DR phenotypes.

Effect of aerobic exercise training on blood pressure sensitivity to dietary sodium in older hypertensives.

Although aerobic exercise training has been shown to lower blood pressure (BP) in older adults, its effect on BP sensitivity to dietary sodium (Na(+)) is unknown. Therefore, the present study was undertaken to examine the effect of aerobic exercise training on BP sensitivity to dietary Na(+) in older hypertensive individuals. Blood pressure was measured after 8 days of low (20 mEq) and high (200 mEq) Na(+) diets in 31 older (63+/-7 years, mean+/-standard deviation), hypertensive (152+/-11/88+/-5 mm Hg) individuals at baseline and following 6 months of aerobic exercise training (at 75% VO(2)max, 3 times/week, 40 min/session). Subjects were grouped on the basis of the difference in mean arterial BP (MAP) between diets (Na(+) sensitive: >or=5 mm Hg increase in MAP on high Na(+), n=20; Na(+) resistant: <5 mm Hg increase in MAP on the high Na(+) diet, n=11). Following 6 months of aerobic exercise training, there was a significant increase in maximal aerobic capacity (VO(2)max: 18.3+/-3.8 vs 20.7+/-4.2 ml/kg/min, P<0.017). Aerobic exercise training had a significant (P=0.02) effect on Na(+) sensitivity status, with the proportion of Na(+)-resistant individuals increasing from 35% at baseline to 61% following the 6-month aerobic exercise training programme. This study demonstrates the importance of physical activity on BP sensitivity to dietary Na(+).

A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas.

Pain from pancreatitis or pancreatic cancer can be both chronic and severe although little is known about the mechanisms that generate and maintain this pain. To define the peripheral sensory and sympathetic fibers involved in transmitting and modulating pancreatic pain, immunohistochemistry and confocal microscopy were used to examine the sensory and sympathetic innervation of the head, body and tail of the normal mouse pancreas. Myelinated sensory fibers were labeled with an antibody raised against 200 kD neurofilament H (clone RT97), thinly myelinated and unmyelinated peptidergic sensory fibers were labeled with antibodies raised against calcitonin gene-related peptide (CGRP) and post-ganglionic sympathetic fibers were labeled with an antibody raised against tyrosine hydroxylase (TH). RT97, CGRP, and TH immunoreactive fibers were present in parenchyma of the head, body and tail of the pancreas with the relative density of both RT97 and CGRP expressing fibers being head>body>tail, whereas for TH, a relatively even distribution was observed. In all three regions of the pancreas, RT97 fibers were associated mainly with large blood vessels, the CGRP fibers were associated with the large- and medium-sized blood vessels and the TH were associated with the large- and medium-sized blood vessels as well as capillaries. In addition to this extensive set of sensory and sympathetic nerve fibers that terminate in the pancreas, there were large bundles of en passant nerve fibers in the dorsal region of the pancreas that expressed RT97 or CGRP and were associated with the superior mesenteric plexus. These data suggest the pancreas receives a significant sensory and sympathetic innervation. Understanding the factors and disease states that sensitize and/or directly excite the nerve fibers that terminate in the pancreas as well as those that are en passant may aid in the development of therapies that more effectively modulate the pain that frequently accompanies diseases of the pancreas, such as pancreatitis and pancreatic cancer.

Antenatal psychiatric illness and adequacy of prenatal care in an ethnically diverse inner-city obstetric population.

OBJECTIVE: This study assessed the prevalence of antenatal psychiatric illness in low-income, ethnically diverse patients in an urban obstetric clinic and examined associations between positive psychiatric screens and inadequate utilization of prenatal care. METHODS: Bilingual research assistants administered the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire and the Mood Disorder Questionnaire to 154 English- and Spanish-speaking pregnant patients attending routine prenatal visits. We assessed associations between patient characteristics, current and past psychiatric diagnoses, and utilization of prenatal care. RESULTS: Forty-five (29%) women screened positive for criteria for current psychiatric disorders with the highest rates for major or minor depression (26%) and anxiety disorders (10%). Inadequate prenatal care utilization was significantly associated with past psychiatric history and domestic abuse in the last year, but not with current psychiatric diagnosis, alcohol abuse, age, primiparity, marital status, receipt of government assistance, or unplanned pregnancy. Even after adjustment for possible confounding risk factors (e.g. past substance abuse, single marital status, unstable housing, education less than high school, and having other children), past psychiatric history was still significantly associated with inadequate prenatal care utilization and delayed initiation of care. CONCLUSIONS: A high percentage of disadvantaged pregnant women meet screening criteria for psychiatric disorders when screened during routine prenatal visits. Screening for past psychiatric history in routine prenatal visits could identify patients at risk for inadequate utilization of prenatal care.

Tau suppression in a neurodegenerative mouse model improves memory function.

Neurofibrillary tangles (NFTs) are the most common intraneuronal inclusion in the brains of patients with neurodegenerative diseases and have been implicated in mediating neuronal death and cognitive deficits. Here, we found that mice expressing a repressible human tau variant developed progressive age-related NFTs, neuronal loss, and behavioral impairments. After the suppression of transgenic tau, memory function recovered, and neuron numbers stabilized, but to our surprise, NFTs continued to accumulate. Thus, NFTs are not sufficient to cause cognitive decline or neuronal death in this model of tauopathy.

Ongoing horizontal and vertical transmission of virulence genes and papA alleles among Escherichia coli blood isolates from patients with diverse-source bacteremia.

The phylogenetic distributions of multiple putative virulence factors (VFs) and papA (P fimbrial structural subunit) alleles among 182 Escherichia coli blood isolates from patients with diverse-source bacteremia were defined. Phylogenetic correspondence among these strains, the E. coli Reference (ECOR) collection, and other collections of extraintestinal pathogenic E. coli (ExPEC) was assessed. Although among the 182 bacteremia isolates phylogenetic group B2 predominated, exhibited the greatest concentration of individual VFs, and contained the largest number of familiar virulent clones, other phylogenetic groups exhibited greater concentrations of certain VFs than did group B2 and included several additional virulent clones. Certain of the newly detected VF genes, e.g., fyuA (yersiniabactin; 76%) and focG (F1C fimbriae; 25%), were as prevalent or more prevalent than their more familiar traditional counterparts, e.g., iut (aerobactin; 57%) and sfaS (S fimbriae; 14%), thus possibly offering additional useful targets for preventive interventions. Considerable diversity of VF profiles was observed at every level within the phylogenetic tree, including even within individual lineages. This suggested that many different pathways can lead to extraintestinal virulence in E. coli and that the evolution of ExPEC, which involves extensive horizontal transmission of VFs and continuous remodeling of pathogenicity-associated islands, is a highly active, ongoing process.

Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with a first or recurrent episode of cystitis.

To identify bacterial predictors of recurrence and/or persistence in acute cystitis, extended virulence genotypes were compared with clonal background and epidemiologic status among 74 Escherichia coli urine isolates from women with first or recurrent episodes of urinary tract infection (UTI). Sequential isolates from patients with recurrent UTI were classified, using macrorestriction analysis, as having caused an isolated recurrence versus a single or multiple same-strain recurrences. papA, papG allele II, iha, and iutA predicted multiple same-strain recurrences, whereas nfaE and the absence of sfaS or fyuA predicted isolated recurrences. Phylogenetic group B2 accounted for 70% of isolates and for most of the putative virulence factors (VFs) studied. The meningitis-associated O18:K1:H7 clonal group comprised 18% of isolates, exhibited multiple VFs, and caused "once-only" recurrences less commonly than did other strains. These findings identify specific VFs and clonal groups against which preventive interventions might be beneficial and illustrate the importance of delineating pathogenetically relevant subgroups within the "recurrent cystitis" population.

Phylogenetic and pathotypic similarities between Escherichia coli isolates from urinary tract infections in dogs and extraintestinal infections in humans.

Seventeen Escherichia coli isolates from dogs with urinary tract infection (UTI) were characterized with respect to phylogenetic background and virulence genotype and were compared with the E. coli reference (ECOR) collection and with human clinical isolates with similar serotypes from patients with diverse extraintestinal infections. Most of the canine urine isolates were from (virulence-associated) E. coli phylogenetic groups B2 or D, expressed papG allele III, and exhibited numerous other putative virulence genes that are characteristic of human extraintestinal pathogenic E. coli (ExPEC). Close phylogenetic and pathotypic correspondence was documented within 5 clonal groups among individual canine and human isolates, including archetypal human ExPEC strains CFT073 (O6:K2:H1), 536 (O6:K15:H31), and J96 (O4:K-:H5). These findings suggest that canine UTI isolates, rather than being dog-specific pathogens, as previously suspected, may pose an infectious threat to humans. Commonality between canine and human ExPEC has potentially important implications for disease prevention, antibiotic resistance avoidance, and studies of pathogenesis.

Revascularization and quality of life for patients with limb-threatening ischemia.

Traditional outcomes following revascularization for chronic critical limb ischemia consider limb retention and hemodynamic results. Health-related quality of life is not measured. This study was undertaken to determine if surgery for chronic critical limb ischemia improves health-related quality of life. Forty-six patients undergoing revascularization (anklebrachial index <0.4 for nondiabetics, ankle-brachial index <0.6 for diabetics and rest pain or nonhealing ischemic ulcers) completed pre- and postoperative Short-Form 36 questionnaires, which were used to assess health-related quality of life in patients undergoing arterial reconstruction for chronic critical limb ischemia. Patients reported a mild improvement in functional status postoperatively, and overall low health-related quality of life. Health-related quality of life is slow to show progress following revascularization. Health-related quality of life should become an important outcomes end point.