Does DCD Donor Time-to-Death Affect Recipient Outcomes? Implications of Time-to-Death at a High-Volume Center in the United States.

For donation after circulatory death (DCD), many centers allow 1 h after treatment withdrawal to donor death for kidneys. Our center has consistently allowed 2 h. We hypothesized that waiting longer would be associated with worse outcome. A single-center, retrospective analysis of DCD kidneys transplanted between 2008 and 2013 as well as a nationwide survey of organ procurement organization DCD practices were conducted. We identified 296 DCD kidneys, of which 247 (83.4%) were transplanted and 49 (16.6%) were discarded. Of the 247 recipients, 225 (group 1; 91.1%) received kidneys with a time to death (TTD) of 0-1 h; 22 (group 2; 8.9%) received grafts with a TTD of 1-2 h. Five-year patient survival was 88.8% for group 1, and 83.9% for group 2 (p = 0.667); Graft survival was also similar, with 5-year survival of 74.1% for group 1, and 83.9% for group 2 (p = 0.507). The delayed graft function rate was the same in both groups (50.2% vs. 50.0%, p = 0.984). TTD was not predictive of graft failure. Nationally, the average maximum wait-time for DCD kidneys was 77.2 min. By waiting 2 h for DCD kidneys, we performed 9.8% more transplants without worse outcomes. Nationally, this practice would allow for hundreds of additional kidney transplants, annually.

A survey of Canadian public health personnel regarding knowledge, practice and education of zoonotic diseases.

Zoonoses, diseases that can spread under natural conditions between humans and other animals, are become a major public health concern in many countries including Canada. In Canada, investigations of zoonotic disease incidents are often conducted by public health inspectors (PHIs). However, little is known about PHIs' knowledge of transmission of zoonotic pathogens, their perceptions of zoonotic disease importance or their education regarding zoonotic diseases. The objective of this study was therefore to assess the knowledge, perceptions and education of Canadian PHIs regarding zoonotic diseases. Data were collected from December 2008-January 2009 using an internet-based survey distributed to members of the Canadian Institute of Public Health Inspectors national listserv. Responses were received from 229 PHIs in four provinces, with a response rate of approximately 20%. The majority of respondents reported at least 10 years of experience in the public health sector, 80% (181/225) were in frontline positions, and 62% (137/222) were routinely involved in investigations of infectious diseases. Two-thirds believed that the importance of zoonotic diseases with regards to public health would increase in the next 5 years. Whilst most respondents were able to correctly identify animals capable of directly transmitting common zoonotic pathogens, there were gaps in knowledge, particularly with regard to rabies and transmission of gastrointestinal pathogens by companion animals. PHIs tended to feel that their training on zoonotic diseases prior to working as PHIs was deficient in some areas, or left some room for improvement. Their responses also suggested that there is a need for improvement in both the quantity and the quality of continuing education on zoonotic diseases. In particular, less than one-third of PHIs received ongoing continuing education regarding zoonotic diseases, and of those that did, nearly two-thirds rated the quantity and quality as only fair.

Applications of accelerator MS in pediatric drug evaluation.

Accelerator MS (AMS) provides a novel method for obtaining and analyzing pharmacokinetics and pharmacodynamics in children. This paper reviews the scientific and ethical rationale for AMS in pediatric trials, the regulatory framework and general considerations with some specific examples of pediatric clinical trials using AMS. Microdosing in the context of this article refers to studies using a negligible amount (nanocuries) of (14)C as tracer, and AMS as a quantitative technique. The technology is by no means a panacea for the deficiency in pediatric clinical research; however, it lessens the challenges and provides the most quantitative tool for pediatric pharmacology studies.

Video observation of hand hygiene practices at a petting zoo and the impact of hand hygiene interventions.

Petting zoos are popular attractions, but can also be associated with zoonotic disease outbreaks. Hand hygiene is critical to reducing disease risks; however, compliance can be poor. Video observation of petting zoo visitors was used to assess animal and environmental contact and hand hygiene compliance. Compliance was also compared over five hand hygiene intervention periods. Descriptive statistics and multivariable logistic regression were used for analysis. Overall hand hygiene compliance was 58% (340/583). Two interventions had a significant positive association with hand hygiene compliance [improved signage with offering hand sanitizer, odds ratio (OR) 3·38, P<0·001; verbal hand hygiene reminders, OR 1·73, P=0·037]. There is clearly a need to improve hand hygiene compliance at this and other animal exhibits. This preliminary study was the first to demonstrate a positive impact of a hand hygiene intervention at a petting zoo. The findings suggest that active, rather than passive, interventions are more effective for increasing compliance.

What we still do not know about adrenal vein sampling for primary aldosteronism.

During the last two decades, primary aldosteronism has emerged as the most common cause of secondary hypertension, and advances in the diagnosis and treatment of this condition have improved patient care substantially. A major stumbling block in the evaluation and management of these patients, which ultimately guides treatment and prognosis, is answering the question, "Which adrenal gland(s) produce aldosterone?" Adrenal vein sampling has emerged as the only reliable method to determine the answer to this question; however, the methodology and criteria for lateralization have been determined empirically with little prospective data. The major remaining controversies surrounding adrenal vein sampling include: who should perform and who should undergo the procedure; what criteria should be used to define a successful study and lateralization of aldosterone production; whether cosyntropin should be infused during the procedure and how; and what to do when results are ambiguous? This article reviews some of the advances in the execution of this procedure, the variations in procedure, the data that fuel the controversies, and the issues that need to be resolved in the future.

Successful kidney transplantation from a donation after cardiac death donor with an ileal conduit.

Kidney transplantation is the treatment of choice for those affected by end-stage renal disease. Consent for organ donation continues to be one of the greatest challenges to transplanting more patients waiting for a life-saving transplant. In an attempt to increase the donor pool for patients on kidney transplant waiting lists, transplant surgeons and physicians have expanded their acceptance criteria to include expanded criteria donors, donation after cardiac death donors, as well as those donors who present unique technical challenges to organ recovery. Here we report a successful kidney transplant from a kidney donor who died from cardiac causes and who previously underwent an ileal conduit for a neurogenic urinary bladder secondary to a spinal cord injury.

Impaired PTPN13 phosphatase activity in spontaneous or HPV-induced squamous cell carcinomas potentiates oncogene signaling through the MAP kinase pathway.

Human papillomaviruses (HPVs) are a causative factor in over 90% of cervical and 25% of head and neck squamous cell carcinomas (HNSCCs). The C terminus of the high-risk HPV 16 E6 oncoprotein physically associates with and degrades a non-receptor protein tyrosine phosphatase (PTPN13), and PTPN13 loss synergizes with H-Ras(V12) or ErbB2 for invasive growth in vivo. Oral keratinocytes that have lost PTPN13 and express H-Ras(V12) or ErbB2 show enhanced Ras/RAF/MEK/Erk signaling. In co-transfection studies, wild-type PTPN13 inhibited Ras/RAF/MEK/Erk signaling in HEK 293 cells that overexpress ErbB2, EGFR or H-Ras(V12), whereas an enzymatically inactive PTPN13 did not. Twenty percent of HPV-negative HNSCCs had PTPN13 phosphatase mutations that did not inhibit Ras/RAF/MEK/Erk signaling. Inhibition of Ras/RAF/MEK/Erk signaling using MEK inhibitor U0126 blocked anchorage-independent growth in cells lacking PTPN13. These findings show that PTPN13 phosphatase activity has a physiologically significant role in regulating MAP kinase signaling.

Retrospective multicentre study of methicillin-resistant Staphylococcus aureus infections in 115 horses.

REASONS FOR PERFORMING STUDY: Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging veterinary and zoonotic pathogen, associated with increasing reports of disease in horses. OBJECTIVES: To provide an overview of the characteristics of clinical MRSA infections in horses. METHODS: A retrospective case study was performed on 115 horses admitted to 6 participating veterinary teaching hospitals in Canada and the United States between 2000 and 2006, and diagnosed with clinical MRSA infection. Descriptive statistics, univariate and multivariable analyses for community- (CA) vs. hospital-associated (HA) MRSA infections, and survival vs. nonsurvival at discharge were performed. RESULTS: The age range of MRSA-infected horses was zero (born in hospital) to 31 years. HA (58/114, 50.9%) and CA infections (56/114, 49.1%) were equally common. Infection of surgical incisions was most frequently reported (44/115, 38.0%). Overall 93/111 (83.8%) cases survived to discharge. Previous hospitalisation and treatment with gentamicin were associated significantly with CA-MRSA, whereas infected incision sites were associated significantly with HA-MRSA. Factors significantly associated with nonsurvival included i.v. catheterisation, CA-MRSA infection and dissemination of infection to other body sites. CONCLUSIONS: Equine MRSA infections have a broad range of clinical presentations, appear to be primarily opportunistic and the overall prognosis for survival to discharge is good. POTENTIAL RELEVANCE: These results should help direct future research with regard to investigation of risk factors for equine MRSA infection in community and hospital populations.

Passive cooling to initiate hypothermia for transported encephalopathic newborns.

Two newborns at high risk for severe encephalopathy were passively cooled by discontinuing the supplied heat from a radiant warmer. Cooling was attempted in both babies (successfully in one) before the arrival of the neonatal transport team. Both infants had core temperatures of approximately 34 degrees C on arrival at the NICU. Passive cooling may be an effective method to initiate cooling very early in the course of encephalopathy.

The 'distal-dorsal difference': a thermographic parameter by which to differentiate between primary and secondary Raynaud's phenomenon.

OBJECTIVE: To test the hypothesis that in a patient with Raynaud's phenomenon (RP), a difference of >1 degrees C between the fingertips and the dorsum of the hand ['distal-dorsal difference' (DDD), fingers cooler] is specific for underlying structural vascular disease as occurs in systemic sclerosis (SSc), and to evaluate other thermographic parameters in the separation of secondary from primary RP. METHODS: A retrospective analysis of the case notes and thermography results of patients attending thermography, primarily over a 2-yr period. Multinomial logistic regression was used to ascertain whether thermography variables differed between groups with primary RP (56 patients), undifferentiated connective tissue disease (21 patients) and SSc (45 patients), with adjustment for age, sex and smoking. RESULTS: A DDD >1 degrees C in any finger at 30 degrees C had a positive predictive value of 70%, and a negative predictive value of 82%, in identifying the patient with RP secondary to SSc. From the results of the multinomial logistic regression, a score was derived incorporating age, number of fingers with DDD >1 degrees C at 30 degrees C and maximum rewarming gradient. This score (with a suitable cut-off) was 82% sensitive and 82% specific in identifying RP secondary to SSc, with a positive predictive value of 73% and a negative predictive value of 89%. CONCLUSION: Parameters derived from thermography (incorporating both a heat and cold challenge) aid in the prediction of SSc in patients with RP.

Methicillin-resistant staphylococcal colonization in clinically normal dogs and horses in the community.

AIMS: To evaluate the prevalence of methicillin-resistant staphylococcal (MRS) colonization in clinically normal dogs and horses in the community. METHODS AND RESULTS: Three hundred clinically normal horses and 200 clinically normal dogs were enrolled. One nasal swab was collected from each horse. Two swabs were taken from each dog: (i) from an anterior nare, and (ii) a combination of the perineal area and 0.5 cm into the anus. Enrichment cultures were performed. Methicillin-resistant Staphylococcus aureus (MRSA) was not identified. Methicillin-resistant Staphylococcus intermedius (MRSI) was isolated from the nasal swab from three dogs. Methicillin-resistant coagulase negative staphylococci (MRCoNS) were isolated from 126/300 (42%) horses and 26/200 (13%) dogs. CONCLUSIONS: At present MRSI is not considered to be a significant zoonotic concern; however, it may become an important pathogen in dogs. MRCoNS mostly cause disease in compromised human or animal hosts. However, these bacteria can serve as reservoirs of resistance determinants in the community, which could lead to the emergence of novel MRSA strains. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of the prevalence of MRS colonization in clinically normal dogs in a community setting. Continued surveillance is indicated to determine whether MRSA will emerge in the animal population and become a concern for animal disease and zoonotic infection.

Detection and occurrence of antimicrobially resistant E. coli in groundwater on or near swine farms in eastern North Carolina.

The use of antibiotics for growth promotion and disease treatment by the commercial swine industry has led to high proportions of multiple antibiotic-resistant enteric bacteria being shed by these animals and concerns about the environmental spread of these bacteria. A study was conducted to quantify the extent of release of antibiotic-resistant E. coli from swine farms into groundwater. Four study sites, two swine farms and two reference sites (crop farms), with known groundwater flow paths were screened for E. coli four times over the course of one and a half years. A total of 100 biochemically-confirmed E. coli were collected from the four sites. There were statistically significantly higher E. coli levels at the two swine farm sites than at the reference sites. The bacterial isolates were tested for antibiotic resistance using a panel of 17 drugs that are typical of human and veterinary use. There were 19 and 71 E. coli isolates from swine farms #1 and #2, respectively, with most (68%) being resistant to 1 -6 antimicrobials. Only one E. coli isolate from each of the reference sites showed antimicrobial resistance traits. The results of this study demonstrate that antibiotic-resistant E. coli strains are present in groundwaters of swine farms with a typical lagoon and land application system for waste management.

Proarrhythmia.

The concept that antiarrhythmic drugs can exacerbate the cardiac rhythm disturbance being treated, or generate entirely new clinical arrhythmia syndromes, is not new. Abnormal cardiac rhythms due to digitalis or quinidine have been recognized for decades. This phenomenon, termed "proarrhythmia," was generally viewed as a clinical curiosity, since it was thought to be rare and unpredictable. However, the past 20 years have seen the recognition that proarrhythmia is more common than previously appreciated in certain populations, and can in fact lead to substantially increased mortality during long-term antiarrhythmic therapy. These findings, in turn, have moved proarrhythmia from a clinical curiosity to the centerpiece of antiarrhythmic drug pharmacology in at least two important respects. First, clinicians now select antiarrhythmic drug therapy in a particular patient not simply to maximize efficacy, but very frequently to minimize the likelihood of proarrhythmia. Second, avoiding proarrhythmia has become a key element of contemporary new antiarrhythmic drug development. Further, recognition of the magnitude of the problem has led to important advances in understanding basic mechanisms. While the phenomenon of proarrhythmia remains unpredictable in an individual patient, it can no longer be viewed as "idiosyncratic." Rather, gradations of risk can be assigned based on the current understanding of mechanisms, and these will doubtless improve with ongoing research at the genetic, molecular, cellular, whole heart, and clinical levels.

QT interval prolongation and arrhythmia: an unbreakable connection?

QT interval prolongation is incontrovertibly linked to increased risk of arrhythmias but, paradoxically, QT interval prolongation can also be an effective antiarrhythmic strategy and is in fact the goal of class III antiarrhythmic drugs. This discussion examines the cellular effects of QT interval prolongation and proposes that calmodulin kinase II (CaMKII) is a specific cellular proarrhythmic signal that is activated downstream to QT interval prolongation. Inhibition of CaMKII can prevent cellular arrhythmia surrogates and in vivo arrhythmias linked to excessive action potential prolongation, suggesting that QT interval prolongation alone does not fully account for proarrhythmia. This reasoning points to the conclusion that QT interval modulation and prolongation not only grades cellular Ca2+ entry for cardiac contraction but also has the potential to recruit Ca2+-activated signalling molecules. CaMKII is one of these molecules and CaMKII activity is at least partially responsible for the proarrhythmic consequences of excessive QT interval prolongation.

Digital iontophoresis of vasoactive substances as measured by laser Doppler imaging--a non-invasive technique by which to measure microvascular dysfunction in Raynaud's phenomenon.

OBJECTIVE: To test the hypothesis that microvascular vasodilation is impaired in patients with systemic sclerosis (SSc) compared with patients with primary Raynaud's phenomenon (PRP) and healthy controls, using the technique of laser Doppler imaging to quantify blood flow responses to iontophoresis of vasoactive agents. METHODS: Microvascular blood flow was measured by laser Doppler imaging before, during and after 120 s iontophoresis (30 microA) of 1% acetylcholine chloride (ACh, endothelium-dependent) and 1% sodium nitroprusside (NaNP, endothelium-independent). Two adjacent fingers of the left hand were studied, and the procedure then repeated on the right. Ten patients with limited cutaneous SSc (LCSSc), 10 patients with PRP and 11 healthy control subjects were studied. RESULTS: Vasodilation in response to both ACh and NaNP iontophoresis, as measured by 'area under the blood flow.time curve' (AUC), normalized for baseline flux, was similar in the control and PRP groups, but was diminished in the LCSSc group compared with both control and PRP groups (ACh results: control vs LCSSc P = 0.028, PRP vs LCSSc P = 0.005; NaNP results: control vs LCSSc P = 0.004, PRP vs LCSSc P = 0.005). There were no differences between groups in baseline flux values nor in voltages required to drive the 30 microA current. CONCLUSIONS: Both endothelium-dependent and endothelium-independent vasodilation are impaired in patients with LCSSc. Vasodilatory responses in patients with PRP are similar to those in controls. If reproducibility is confirmed to be satisfactory, then these techniques could be used to examine disease progression over time and responsiveness to vasoactive treatment, thus facilitating clinical trials.

Screening of the equine intestinal microflora for potential probiotic organisms.

REASONS FOR PERFORMING STUDY: Probiotics have not been demonstrated to provide any beneficial health effects in horses, possibly because of improper selection of probiotic organisms. This study was designed to identify lactic acid bacteria of equine origin with predetermined beneficial properties which might make them useful as therapeutic probiotics. HYPOTHESIS: A small percentage of lactic acid bacteria that are native to the intestinal tract of horses possess properties that may be useful in the treatment and/or prevention of gastrointestinal disease in horses. METHODS: Faecal samples were collected from healthy mature horses and foals. Lactic acid bacteria were isolated and tested for the ability to grow in acid and bile environments, aerotolerance and in vitro inhibition of enteropathogens. One isolate that possessed these properties was administered orally to healthy mature horses and foals and gastrointestinal survival was assessed. RESULTS: Of the 47 tested organisms, 18 were deemed to be adequately acid- and bile-tolerant. All were aerotolerant. Four organisms markedly inhibited Salmonella spp. One isolate, Lactobacillus pentosus WE7, was subjectively superior and chosen for further study. It was also inhibitory against E. coli, moderately inhibitory against S. zooepidemicus and C. difficile and mildly inhibitory against C. perfringens. After oral administration, this isolate was recovered from the faeces of 8/9 (89%) foals and 7/8 (87.5%) mature horses. CONCLUSIONS: Lactobacillus pentosus WE7 possesses in vitro and in vivo properties that may be useful for the prevention and treatment of enteric disease in horses. POTENTIAL RELEVANCE: The beneficial in vitro and in vivo properties that L. pentosus WE7 possesses indicate that randomised, blinded, placebo-controlled efficacy studies are warranted.

Determining effects of freezing on pasta filata and non-pasta filata mozzarella cheeses by nuclear magnetic resonance imaging.

The formation of ice during freezing of pasta filata and non-pasta filata Mozzarella cheeses, and the spatial redistribution of water T2 relaxation time and the changes of water self-diffusion coefficient (D) within the unfrozen and frozen-stored cheese samples were observed by nuclear magnetic resonance imaging. Images of water spin number density and water T2 relaxation time were obtained using spin-echo imaging pulse sequence. The water self-diffusion coefficient was measured by pulsed-field gradient spin-echo technique. The ice formation was accompanied by loss of signal intensity in the affected areas of the cheese sample. There was a significant change in T2 and D values of water following freezing-thawing, which can be used to characterize the effect of freezing on cheeses. The D values of the frozen-stored pasta filata Mozzarella cheese samples were higher than those for the unfrozen samples. Such a difference was not observed for the non-pasta filata Mozzarella cheese samples. The T2 distributions of frozen-stored pasta filata Mozzarella cheese samples were narrower, and those for the non-pasta filata Mozzarella cheese samples were broader T2. This may be attributed to the microstructure differences between the two cheeses.

Seventeen-point dermal ultrasound scoring system--a reliable measure of skin thickness in patients with systemic sclerosis.

OBJECTIVE: Our objective was to develop a 17-site ultrasound method of measuring skin thickness in patients with systemic sclerosis (SSc) and to assess its inter- and intra-observer variability. METHODS: Dermal thickness (using a 22 MHz ultrasound probe) was measured at 17 sites (corresponding to those assessed in the modified Rodnan skin score) in 39 patients with SSc (26 limited cutaneous, 13 diffuse) and 34 healthy controls. The sum of the thicknesses (at the 17 sites) and the maximal thickness were also documented. Because skin thickness varies between sites, each measurement was converted to a z-score. Inter- and intra-observer variability were assessed in 35 patients/33 controls, and 20 patients/15 controls respectively. RESULTS: Measurement precision was good for the dermal measurements-intraclass correlation coefficients at the 17 sites ranged from 0.65 to 0.94 for the inter-observer variability (0.86 for maximum thickness) and from 0.55 to 0.96 for the intra-observer variability (0.92 for maximum thickness). CONCLUSION: Our results suggest that the 17-point dermal ultrasound scoring system is extremely reliable and may therefore be a useful measure of outcome, including in clinical trials.