Short-term outcome of adrenalectomy in dogs with adrenal gland tumours that did not receive pre-operative medical management.

OBJECTIVE: Review medical records of dogs that underwent adrenalectomy without pre-operative medical management, to examine the peri-operative morbidity and mortality. DESIGN: Case series of 65 dogs. METHODS: Medical records were reviewed. Features recorded included the histologic diagnosis, intra-operative hypertension or tachycardia, requirement for cavotomy, administration of intra- and post-operative corticosteroids, performance of additional surgery and the occurrence of peri-operative complications. Dogs requiring emergency surgery were excluded. RESULTS: Of the 65 dogs, 49 had adrenocortical tumours (11 bilateral), 13 had pheochromocytomas (one bilateral) and three dogs had tumours in both adrenal glands of a different tumour type. Five dogs had caudal vena cava invasion and 33 had additional procedures performed at the same time. Mortality occurred in 1/65 dogs (1.5%; 95% CI 0.03%-8.2%), major complications were identified in 1/65 dogs (1.5%; 95% CI 0.03%-8.2%) and minor complications occurred in 10/53 dogs (15%; 95% CI 8.6%-26%). CONCLUSION: Based on the limited peri-operative complications and low mortality in this pre-operatively untreated cohort, and based on critique of the available literature, the added value afforded by pre-operative treatment is questioned. With appropriate management, adrenal tumours can be removed with few peri-operative complications and low mortality.

Rate of dyslipidemia higher among women living with HIV: A comparison of metabolic and cardiovascular health in a cohort to study aging in HIV.

OBJECTIVES: Combination antiretroviral therapy has largely restored the lifespan of persons living with HIV. Data suggest early comorbidities of aging in this population. Past studies focused on men; limited data exist regarding the prevalence of dyslipidaemia in women living with HIV (WLWH). We investigated the prevalence of cardiometabolic abnormalities among WLWH and HIV-negative women in the Children and Women: Antiretrovirals and Markers of Aging (CARMA) cohort, and their relationships to cellular aging markers. METHODS: We conducted a cross-sectional analysis of nonpregnant female patients (156 WLWH and 133 HIV-negative controls, aged 12-69 years) enrolled in CARMA between 2013 and 2017. The Framingham risk score (FRS) and the prevalences of hypertension, diabetes, metabolic syndrome and dyslipideamia were determined using self-report, anthropometrics, chart review and laboratory data. Cellular aging was determined by assessing leukocyte telomere length and blood mitochondrial DNA content. Diagnoses were based on current Canadian guidelines and definitions. RESULTS: HIV-infected status was associated with dyslipidaemia [odds ratio (OR) 2.89; 95% confidence interval (CI) 1.69-5.01], but not diabetes, higher FRS, hypertension or metabolic syndrome. The median age was 43.5 [interquartile range (IQR) 36.8-50.9] years in WLWH and 46.2 (IQR 30.3-54.9) years in HIV-negative controls. WLWH were less likely to be menopausal or use alcohol, and more often had hepatitis C virus infection or a current or past smoking history. Lower mitochondrial DNA content was associated with metabolic syndrome; no other associations were noted between cardiometabolic abnormalities and markers of cellular aging. CONCLUSIONS: Despite their relatively young age, almost two-thirds of WLWH had dyslipidaemia, a significantly greater proportion than in controls. Strategies to address dyslipidaemia and decrease smoking rates may improve long-term outcomes among WLWH.

MED13L-related intellectual disability: involvement of missense variants and delineation of the phenotype.

Molecular anomalies in MED13L, leading to haploinsufficiency, have been reported in patients with moderate to severe intellectual disability (ID) and distinct facial features, with or without congenital heart defects. Phenotype of the patients was referred to "MED13L haploinsufficiency syndrome." Missense variants in MED13L were already previously described to cause the MED13L-related syndrome, but only in a limited number of patients. Here we report 36 patients with MED13L molecular anomaly, recruited through an international collaboration between centers of expertise for developmental anomalies. All patients presented with intellectual disability and severe language impairment. Hypotonia, ataxia, and recognizable facial gestalt were frequent findings, but not congenital heart defects. We identified seven de novo missense variations, in addition to protein-truncating variants and intragenic deletions. Missense variants clustered in two mutation hot-spots, i.e., exons 15-17 and 25-31. We found that patients carrying missense mutations had more frequently epilepsy and showed a more severe phenotype. This study ascertains missense variations in MED13L as a cause for MED13L-related intellectual disability and improves the clinical delineation of the condition.

Do contamination of and exposure to chicken meat and water drive the temporal dynamics of Campylobacter cases?

Campylobacteriosis, the most frequent bacterial enteric disease, shows a clear yet unexplained seasonality. The study purpose was to explore the influence of seasonal fluctuation in the contamination of and in the behaviour exposures to two important sources of Campylobacter on the seasonality of campylobacteriosis. Time series analyses were applied to data collected through an integrated surveillance system in Canada in 2005-2010. Data included sporadic, domestically-acquired cases of Campylobacter jejuni infection, contamination of retail chicken meat and of surface water by C. jejuni, and exposure to each source through barbequing and swimming in natural waters. Seasonal patterns were evident for all variables with a peak in summer for human cases and for both exposures, in fall for chicken meat contamination, and in late fall for water contamination. Time series analyses showed that the observed campylobacteriosis summer peak could only be significantly linked to behaviour exposures rather than sources contamination (swimming rather than water contamination and barbequing rather than chicken meat contamination). The results indicate that the observed summer increase in human cases may be more the result of amplification through more frequent risky exposures rather than the result of an increase of the Campylobacter source contamination.

Hospitalizations associated with salmonellosis among seniors in Canada, 2000-2010.

Salmonella is one of the most prevalent bacteria associated with enteric illness in Canada and seniors are considered a vulnerable population more likely to develop severe illness. In the coming decades, hospitalizations and deaths associated with Salmonella in seniors could represent a challenge due to an aging population in Canada. The numbers of non-typhoidal (NT) Salmonella-related hospitalizations from the Canadian Hospitalization Morbidity Database were analysed for a period of 10 years for seniors. Hospitalization rate calculations and descriptive analyses were performed on variables associated with the burden of hospitalization and compared with the adult age group. Estimates of hospitalizations and deaths associated with domestically acquired Salmonella (accounting for under-reporting) were also calculated. This study found that 50% of the NT Salmonella-related hospitalization and 82% of the deaths recorded in the Canadian adult population occurred in seniors. The length of hospitalization stay was also longer in seniors (7 days) than other adults (4 days). We estimated that each year, 535 hospitalizations and 27 deaths are related to domestically acquired Salmonella in seniors. Senior populations represent a substantial percentage of Salmonella-related hospitalizations and deaths in Canada and the burden associated with those hospitalizations is also greater. This should be considered when developing estimates of medical costs and implementing prevention activities.

Campylobacter spp. Prevalence and Levels in Raw Milk: A Systematic Review and Meta-Analysis.

Campylobacteriosis is the leading bacterial gastrointestinal disease internationally, contributing significantly to the enteric illness burden. Cases have been associated with the consumption of raw milk, a behavior that has garnered attention recently. Estimates of the prevalence and levels of Campylobacter spp. in raw milk are lacking, which hinders risk assessment attempts. This article is a systematic review and meta-analysis of reported prevalence and levels of zoonotic Campylobacter spp. in the raw milk of cows, goats, and sheep in Canada, the United States, Europe, Australia, and New Zealand. The relevant literature was reviewed, and trained reviewers examined the results for inclusion of articles in the meta-analysis. Relevant data (prevalence and/or level of Campylobacter in raw milk, country of origin, animal species, sample source, Campylobacter species identified, etc.) were extracted, and a meta-analysis was performed in Stata v. 12 (Metaprop command). The weighted mean prevalence of Campylobacter spp. in raw milk samples was 1.18%. Subgroup analyses were conducted to examine how prevalence varied by study characteristics, with the highest prevalence values in studies from the United Kingdom (by country, 6.4%), about cows (by animal species, 1.3%), and including samples taken from inline filters (by sample source, 1.75%) and in studies that included species that are not pathogenic to humans (by Campylobacter species, 1.14%). Two articles each included a single Campylobacter level, 0.16 ± 0.3 and approximately 0.047 most probable number per ml. Despite a relatively low prevalence, consumption of raw milk is inherently risky because no treatment has been used to inactivate pathogens. This potential risk further supports maintaining regulations to limit the sales of raw milk.

Methodology for AACT evidence-based recommendations on the use of intravenous lipid emulsion therapy in poisoning

Intravenous lipid emulsion (ILE) therapy is a novel treatment that was discovered in the last decade. Despite unclear understanding of its mechanisms of action, numerous and diverse publications attested to its clinical use. However, current evidence supporting its use is unclear and recommendations are inconsistent. To assist clinicians in decision-making, the American Academy of Clinical Toxicology created a workgroup composed of international experts from various clinical specialties, which includes representatives of major clinical toxicology associations. Rigorous methodology using the Appraisal of Guidelines for Research and Evaluation or AGREE II instrument was developed to provide a framework for the systematic reviews for this project and to formulate evidence-based recommendations on the use of ILE in poisoning. Systematic reviews on the efficacy of ILE in local anesthetic toxicity and non-local anesthetic poisonings as well as adverse effects of ILE are planned. A comprehensive review of lipid analytical interferences and a survey of ILE costs will be developed. The evidence will be appraised using the GRADE system. A thorough and transparent process for consensus statements will be performed to provide recommendations, using a modified Delphi method with two rounds of voting. This process will allow for the production of useful practice recommendations for this therapy.(AU)

Stool submission data to help inform population-level incidence rates of enteric disease in a Canadian community.

Laboratory-based surveillance data is essential for monitoring trends in the incidence of enteric disease. Current Canadian human enteric surveillance systems report only confirmed cases of human enteric disease and are often unable to capture the number of negative test results. Data from 9116 hospital stool specimens from the Waterloo Region in Canada, with a mixed urban and rural population of about 500 000 were analysed to investigate the use of stool submission data and its role in reporting bias when determining the incidence of enteric disease. The proportion of stool specimens positive for Campylobacter spp. was highest in the 15-29 years age group, and in the 5-14 years age group for Salmonella spp. and E. coli O157:H7. By contrast, the age-specific incidence rates were highest for all three pathogens in the 0-4 years age group which also had the highest stool submission rate. This suggests that variations in age-specific stool submission rates are influencing current interpretation of surveillance data.

Age-related variation in limb bone diaphyseal structure among Inuit foragers from Point Hope, northern Alaska.

UNLABELLED: Age-related deterioration of limb bone diaphyseal structure is documented among precontact Inuit foragers from northern Alaska. These findings challenge the concept that bone loss and fracture susceptibility among modern Inuit stem from their transition away from a physically demanding traditional lifestyle toward a more sedentary Western lifestyle. INTRODUCTION: Skeletal fragility is rare among foragers and other traditional-living societies, likely due to their high physical activity levels. Among modern Inuit, however, severe bone loss and fractures are apparently common. This is possibly because of recent Western influences and increasing sedentism. To determine whether compromised bone structure and strength among the Inuit are indeed aberrant for a traditional-living group, data were collected on age-related variation in limb bone diaphyseal structure from a group predating Western influences. METHODS: Skeletons of 184 adults were analyzed from the Point Hope archaeological site. Mid-diaphyseal structure was measured in the humerus, radius, ulna, femur, and tibia using CT. Structural differences were assessed between young, middle-aged, and old individuals. RESULTS: In all bones examined, both females and males exhibited significant age-related reductions in bone quantity. With few exceptions, total bone (periosteal) area did not significantly increase between young and old age in either sex, nor did geometric components of bending rigidity (second moments of area). CONCLUSIONS: While the physically demanding lifestyles of certain traditional-living groups may protect against bone loss and fracture susceptibility, this is not the case among the Inuit. It remains possible, however, that Western characteristics of the modern Inuit lifestyle exacerbate age-related skeletal deterioration.

Assessing multiple foodborne, waterborne and environmental exposures of healthy people to potential enteric pathogen sources: effect of age, gender, season, and recall period.

Information is lacking in Canada on the frequency of exposures of healthy people to enteric pathogen sources (i.e. water, food, animal contact) at the community level. This information is critical to develop more robust risk assessments and prioritize control measures. A 12-month-long cross-sectional telephone survey of 1200 healthy individuals in a sentinel community was performed. Survey respondents were divided into three recall period groups (3, 7, 14 days). The occurrence of 46 exposures (including water, animal contact, environmental contact and high-risk foods) was assessed per recall period. Effect of age, gender, and season on exposures was modelled and frequencies of exposure were extrapolated. Thirty-five exposures had similar occurrences across recall periods. Age was significant for 23 exposures, season for 18, and gender for three. Exposures that vary by age and season (i.e. bottled water, swimming, etc.) warrant consideration when investigating and analysing cases of enteric illness.

Epidemiological and clinical description of the top three reportable parasitic diseases in a Canadian community.

This study provides a comprehensive epidemio-clinical picture of sporadic, domestically acquired cases of amoebiasis, cryptosporidiosis and giardiasis in one Canadian community based on patient symptom, outcome and exposure data from an enhanced surveillance system. It yields valuable data for estimating the burden of those diseases including the proportion of bloody diarrhoea, hospitalization, and disease duration. Age differences were observed by incidence rate and for some clinical information and exposures to risk factors. For each of the three diseases, the animal/environment-to-person route was the most common possible main transmission route according to the exposure reported, whereas the person-to-person route was the least common. Exposure was higher for the 10-24 years age group of giardiasis cases for swimming in recreational waters (79%) and attending a barbeque (50%). Therefore, comparisons between groups of cases or extrapolation of results when estimating the burden of illness should be adjusted for age.

The effects of microporosity on osteoinduction of calcium phosphate bone graft substitute biomaterials.

The effect of increasing strut porosity on the osteoinductive ability of silicate substituted calcium phosphate (SiCaP) biomaterials was investigated in an ectopic ovine model. Implants with strut porosities of 22.5%, 32.0% and 46.0% were inserted into the parapsinalis muscle. At 8, 12 and 24 weeks histological sections were prepared. Sections were examined using backscattered scanning electron microscopy and un-decalcified histology. Bone area, implant area and bone-implant contact were quantified. At 8 weeks there was no significant difference between the groups in terms of bone area and implant area. However at 12 weeks, the amount of bone formation observed was significantly greater in SiCaP-46 (6.17 ± 1.51%) when compared with SiCaP-22.5 (1.33 ± 0.84%) p=0.035. Results also showed significantly increased amounts of bone-implant contact to the SiCaP-46 scaffold (3.30 ± 1.17%) compared with SiCaP-22.5 (0.67 ± 0.52%, p=0.043) at 8 weeks and 12 weeks; (SiCaP-46 (21.82 ± 5.59%) vs SiCaP-22.5 (3.06 ± 1.89%), p=0.012). At 24 weeks, bone formation and graft resorption had significantly increased in all groups so that the level of bone formation in the SiCaP-46 group had increased 75-fold to 30.05 ± 8.38%. Bone formation was observed in pores <10 µm. Results suggest that bone graft substitute materials with greater strut porosity are more osteoinductive.

Integrated surveillance and potential sources of Salmonella enteritidis in human cases in Canada from 2003 to 2009.

Salmonella enteritidis has emerged as the most prevalent cause of human salmonellosis in Canada. Recent trends of S. enteritidis subtypes and their potential sources were described by integrating Salmonella data from several Canadian surveillance and monitoring programmes. A threefold increase in S. enteritidis cases from 2003 to 2009 was identified to be primarily associated with phage types 13, 8 and 13a. Other common phage types (4, 1, 6a) showed winter seasonality and were more likely to be associated with cases linked to international travel. Conversely, phage types 13, 8 and 13a had summer seasonal peaks and were associated with cases of domestically acquired infections. During agri-food surveillance, S. enteritidis was detected in various commodities, most frequently in chicken (with PT13, PT8 and PT13a predominating). Antimicrobial resistance was low in human and non-human isolates. Continued integrated surveillance and collaborative prevention and control efforts are required to mitigate future illness.

A modified case-control study of cryptosporidiosis (using non-Cryptosporidium-infected enteric cases as controls) in a community setting.

Data from the first sentinel site (Waterloo Region, Ontario) of the Canadian Integrated Enteric Disease Surveillance System (C-EnterNet) were used in a secondary-based case-control study of laboratory-confirmed Cryptosporidium infections to study the role of various exposure factors. The incidence of cryptosporidiosis in Waterloo Region was almost double both the provincial and national rates. Persons ill with one of nine other enteric infections (amoebiasis, campylobacteriosis, cyclosporiasis, giardiasis, listeriosis, salmonellosis, shigellosis, verotoxigenic E. coli infections, yersiniosis) captured by the surveillance system were used as the control group. Of 1204 cases of enteric illness in the sentinel area between April 2005 and December 2007, 36 cases and 803 controls were selected after excluding outbreak and international travel-related cases. Univariable analyses (Pearson chi2 and Fisher's exact tests) and multivariable logistic regression were performed. Results of the multivariable analysis found that cryptosporidiosis was associated with swimming in a lake or river (OR 2.9, 95% CI 1.2-7.4), drinking municipal water (a potential surrogate for urban respondents vs. rural) (OR 2.4, 95% CI 1.04-5.7), and having a family member with a diarrhoeal illness (OR 2.9, 95% CI 1.3-6.4).

Water consumption habits of a south-western Ontario community.

A cross-sectional telephone survey (n = 2,332) was performed to better understand the drinking water consumption patterns among residents in Waterloo Region, Ontario, Canada. We investigated the daily volume of water consumed (including tap and bottled) and factors related to that consumption. In addition, we investigated the daily volume of cold tap water consumed by those respondents who consumed no bottled water and the factors that influence this consumption. Among study respondents, 51% exclusively drank tap water, 34% exclusively drank bottled water and 14.5% drank both, with 10 to 75% of all cold water consumed in the previous day being bottled. The mean volume of water consumed in a day (including bottled and tap water) was 1.39 l. Among those who reported to exclusively consume tap water, the mean daily volume of tap water consumed was 1.45 l. The daily amount of cold water consumed in a day was lower for older respondents, more markedly for men than women. More educated respondents consumed more water during the day. Roughly 45% of households reported that they used a carbon filter to treat their water. Roughly 5% of respondents used advanced home treatment devices, including ultraviolet light, reverse osmosis, ozonation or distillation.

Symptomatic venous sinus thrombosis following bone wax application to emissary veins.

A retrosigmoid craniectomy was performed for acoustic neuroma during which bone wax was used to control emissary vein bleeding. Postoperatively the patient developed an extensive venous thrombosis due to wax in the sigmoid sinus from which she recovered. We discuss this rare complication of posterior fossa surgery.

Pericardial effusions in children with severe protein energy malnutrition resolve with therapeutic feeding: a prospective cohort study.

BACKGROUND: Malnutrition underlies 50% of paediatric morbidity and mortality in sub-Saharan Africa. It is important to look for the underlying causes of the malnutrition, and some clinicians have assumed that the presence of a pericardial effusion indicates underlying tuberculosis (TB). We wished to see how common pericardial effusions are in malnourished children and how their presence or size is related to peripheral oedema or the type of malnutrition of the child, HIV status or to underlying TB. METHODS: We prospectively studied a cohort of children at a regional nutritional rehabilitation unit in Malawi. Echocardiography on admission and follow-up 4 weeks later was performed. During this interval children received therapeutic feeding and any other required medical care. The children were grouped into group 1 (marasmus), group 2 (marasmus with TB), group 3 (marasmic kwashiorkor), group 4 (marasmic kwashiorkor with TB), group 5 (kwashiorkor) and group 6 (kwashiorkor with TB). RESULTS: Of the 89 children who were enrolled, 28 were marasmic (eight also had TB), 29 had marasmic kwashiorkor (six with TB) and 32 had kwashiorkor (four with TB). In all the children who had a pericardial effusion, its size was greatest at presentation. The overall reduction in pericardial effusion size after 4 weeks of nutritional therapy was significant (2.9 mm change, range 0 to 8.4 mm, p = 0.002). The greatest change in pericardial effusion size was in the children with most peripheral oedema compared with those with no oedema (2.7 mm versus 1.0 mm, p = 0.017). CONCLUSIONS: In severely malnourished children pericardial effusions are common, larger in children with peripheral oedema and respond to nutritional therapy alone.

Formatting antibody fragments to mediate specific therapeutic functions.

Monoclonal antibodies are increasingly being used as therapeutic agents in a wide range of indications, including oncology, inflammation and infectious disease. In most cases the basis of the therapeutic function is the high degree of specificity and affinity the antibody-based drug has for its target antigen. However, the mechanism of action (MOA), the way the drug takes advantage of this specificity to mediate a therapeutic effect, varies considerably from drug to drug. Three basic potential categories of MOAs exist: antagonists, agonists and specific delivery mechanisms to target an active function to a particular cell type. The latter functions include selective cell killing, based on Fc-mediated events, recruitment of effector cells, and drug or radioisotope delivery. The majority of these mechanisms are not necessarily optimally mediated by an IgG structure; clearly, in the case of antibody-dependent cellular cytotoxicity or complement-mediated lysis, Fc is required. However, Fab fragments (the fragment comprising one antigen-binding arm of the Y-shaped IgG molecule) can be formatted to mediate most mechanisms and have the advantage that valency and half-life can be controlled to simplify the drug and address only the mechanism required. Moreover, Fab fragments can be produced in microbial expression systems which address manufacturing issues such as scale of supply and cost of goods.

Prolonged in vivo residence times of antibody fragments associated with albumin.

Antibody fragments can be expressed at a high level in microbial systems, but they may have limited therapeutic value because they are rapidly eliminated from the body. We demonstrate here that site-specific conjugation or binding of bacterially derived Fab' to the long-lived protein serum albumin allows full retention of the antibody's binding characteristics while imparting the albumin's longevity in vivo. In rats the area under the curve for Fab' conjugated to rat serum albumin was 17-fold greater than for the control of Fab' conjugated to cysteine. Again, a bispecific F(ab')(2) with specificity for rat serum albumin showed an area under the curve about 8-fold greater than did a F(ab')(2) without specificity to albumin. Genetic fusions of scFv to albumin were similarly long-lived and could be expressed in yeast to provide the basis of a cost-effective production system.