Psychological consequences of MRI-based screening among women with strong family histories of breast cancer.

PURPOSE: MRI-based screening in women with a ≥ 25% lifetime risk of breast cancer , but no identifiable genetic mutations may be associated with false positives. This study examined the psychological impact of abnormal screens and biopsies in non-mutation carriers participating in high-risk screening with no personal history of breast cancer. METHODS: Non-mutation carriers participating in the High-Risk Ontario Breast Screening Program at two sites were mailed demographic surveys, psychological scales, and chart review consent. Scales included the Consequences of Screening in Breast Cancer questionnaire, Lerman Breast Cancer Worry Scale, and Worry Interference Scale. Missing data were managed with multiple imputation. Multivariable regression was used to assess whether abnormal screens or biopsies were associated with adverse psychological effects. RESULTS: After contacting 465 participants, 169 non-mutation carriers were included. Median age was 46 years (range 30-65). Over a median 3 years of screening, 63.9% of women experienced at least one abnormal screen, and 24.9% underwent biopsies. Statements relating to cancer worry/anxiety scored highest, with 19.5% indicating they worried "a lot". Higher scores among anxiety-related statements were strongly associated with higher dejection scores. Overall, coping and daily functioning were preserved. Women indicated some positive reactions to screening, including improved existential values and reassurance they do not have breast cancer. Abnormal screens and biopsies were not significantly associated with any psychological scale, even after adjustment for patient characteristics. CONCLUSION: Non-mutation carriers undergoing MRI-based screening had considerable baseline anxiety and cancer worry, although daily functioning was not impaired. Abnormal screens and biopsies did not appear to have adverse psychological effects.

Body mass index impacts infection rates in immediate autogenous breast reconstruction.

PURPOSE: Risk of postoperative infection following breast cancer reconstruction warrants consideration of both classic and procedure-specific risk factors. We performed a retrospective chart review of patients with breast cancer over a 10-year period that underwent reconstructive surgery to identify factors that increase risk of postoperative infection. METHODS: Rates of postoperative infection were assessed in primary (immediate or delayed, alloplastic or autogenous) and secondary reconstructive procedures. Patient characteristics, surgical details, and cancer features were analyzed using two-sample t test and Fisher's exact test for continuous and categorical data, respectively. RESULTS: 456 procedures were performed on 264 patients with 29 cases of postoperative infection (6%). Infection was more likely to occur in earlier reconstructive procedures (p < 0.03). Overall, primary reconstructive procedures were associated with a higher infection rate (p = 0.005). Other associated risk factors included: autogenous reconstruction (p < 0.018), length of admission (p < 0.001) and immediate reconstruction (p = 0.01). Subgroup analysis revealed increased risk of infection with immediate autogenous reconstruction (p < 0.03). Furthermore, patients with greater body mass index (BMI) receiving immediate autogenous reconstruction had a greater risk of infection (p < 0.003). Factors unrelated to risk of infection included history of irradiation, smoking, cancer stage, tumor type and tumor size. CONCLUSIONS: Our findings suggest that risk of infection is higher in immediate autogenous reconstructions particularly when patients are overweight (BMI > 30). Our data do not support a relationship between infection and irradiation, features of cancer, or repeated reconstructive procedures. Prospective studies may be required to further validate these findings.

Mouse genetic background is associated with variation in secondary complications after subarachnoid hemorrhage.

Spontaneous subarachnoid hemorrhage (SAH) is a form of hemorrhagic stroke that accounts for approximately 7 % of all strokes worldwide and is associated with mortality in approximately 35 % of cases and morbidity in many of the survivors. Studies have suggested that genetic variations may affect the pathophysiology of SAH. The goal of this study was to investigate the effect of mouse genetic background on brain injury and large artery vasospasm after SAH. SAH was induced in seven inbred strains of mice, and the degree of large artery vasospasm and brain injury was assessed. After 48 h, SAH mice showed a significant reduction in middle cerebral artery diameter and increased neuronal injury in the cerebral cortex compared with sham-operated controls. Mouse strains also demonstrated variable degrees of vasospasm and brain injury. This data suggests that different genetic factors influence how much brain injury and vasospasm occur after SAH. Future investigations may provide insight into the causes of these differences between strains and into which genetic contributors may be responsible for vasospasm and brain injury after SAH.

Resident Exposure and Involvement in Core Procedural Competencies within Pediatric Plastic Surgery.

Introduction: The implementation of competency-based residency training in plastic surgery is underway. Key competencies in plastic surgery have been previously identified, however, within the domain of pediatrics, data suggest limited exposure throughout training for Canadian graduates. This study aims to identify the exposure and involvement of residents in core pediatric cases. Methods: We performed a retrospective, multicenter review of plastic surgery resident case logs (T-Res, POWER, New Innovations) across 10 Canadian, English-speaking training programs between 2004 and 2014. Case logs were coded according to the 8 core pediatric competencies previously identified by a modified Delphi technique. Results: A total of 3061 of 59 405 cases (5.2%) logged by 55 graduating residents were core pediatric procedures with an average of 55.6 ± 23.0 cases logged per resident. The top 3 most commonly logged procedures were cleft lip repair, cleft palate repair, and setback otoplasty. The number of cases per program varied widely with the most at 731 and least at 85 logged cases. Roles across procedures have wide variation and residents are most commonly identified as the assistant rather than surgeon or co-surgeon. Conclusion: These findings highlight variability both within and across residency programs with a paucity of exposure and involvement in pediatric plastic surgery cases. This may present a conflict between current recommendations for residency-specific procedural competencies and true clinical exposure. Further curriculum development and simulation may be of benefit.

Introduction: La formation des résidents fondée sur les compétences est en voie d'être adoptée en chirurgie plastique. Les compétences clés sont d'ailleurs déjà établies, mais dans le domaine de la pédiatrie, les données indiquent que les diplômés canadiens y sont peu exposés pendant leur formation. La présente étude vise à déterminer l'exposition et la participation des résidents aux cas fondamentaux en pédiatrie. Méthodologie: Les chercheurs ont procédé à une analyse multicentrique rétrospective des registres de cas des résidents en chirurgie plastique (T-Res, POWER, New Innovations) de dix programmes de formation anglophones canadiens entre 2004 et 2014. Ils ont codé ces registres en fonction des huit compétences pédiatriques fondamentales préalablement déterminées par une technique Delphi modifiée. Résultats: Au total, 3 061 des 59 405 cas enregistrés (5,2 %) par 55 résidents de dernière année étaient des interventions pédiatriques fondamentales, et chaque résident a enregistré une moyenne de 55,6 ± 23,0 cas. Les trois interventions les plus enregistrées étaient la réparation de la fissure labiale, la réparation de la fissure palatine et l'otoplastie. Le nombre de cas enregistrés variait énormément d'un programme à l'autre, le plus élevé étant de 731 et le plus bas, de 85. Les rôles au cours des interventions étaient très variables, et les résidents étaient davantage qualifiés d'assistants que de chirurgiens ou de cochirurgiens. Conclusion: Ces observations font ressortir la variabilité des pratiques à la fois au sein des programmes de résidence et entre eux et démontrent le peu d'exposition et de participation des résidents aux cas de chirurgie plastique pédiatrique. Elles peuvent révéler un conflit entre les recommandations actuelles en matière de compétences interventionnelles des résidents et la véritable exposition clinique. Il pourrait être utile de voir à l'élaboration plus poussée du programme et des simulations.

Burn Infection and Burn Sepsis.

Background: Infection is the most common complication and cause of death in patients suffering burn injuries. These patients are susceptible to infection and burn wound sepsis secondary to the alterations in their physiology. Diagnosis and management of infections rely on physical examination, cultures, and the pathology of the burn wound. Method: We performed an electronic search for articles in the Google Scholar and PubMed databases using the search terms "burn sepsis," "burn infection," and "burn critical care." Results: Multiple factors increase burn patients' risk of invasive infection and sepsis, including underlying factors and co-morbidities, the percent total body surface area of the burn, delays in burn wound excision, and microbial virulence/bacterial count. Organisms causing burn wound infection differ, depending on the time since injury and its location; and diagnosis is multi-factorial. The most common pathogens remain Staphylococcus and Pseudomonas spp. Conclusion: Overall, the recognition of burn sepsis is based on clinical findings. Treatment consists of a combination of local dressings, early burn excision, and systemic antimicrobial therapy. The mortality rate has decreased significantly over the past 10 years, but continued efforts at timely management and infection prevention are essential.

Gene expression profiling of brain endothelial cells after experimental subarachnoid haemorrhage.

Subarachnoid haemorrhage (SAH) is a type of hemorrhagic stroke that is associated with high morbidity and mortality. New effective treatments are needed to improve outcomes. The pathophysiology of SAH is complex and includes early brain injury and delayed cerebral ischemia, both of which are characterized by blood-brain barrier (BBB) impairment. We isolated brain endothelial cells (BECs) from mice subjected to SAH by injection of blood into the prechiasmatic cistern. We used gene expression profiling to identify 707 unique genes (2.8% of transcripts, 403 upregulated, 304 downregulated, 24,865 interrogated probe sets) that were significantly differentially expressed in mouse BECs after SAH. The pathway involving prostaglandin synthesis and regulation was significantly upregulated after SAH, including increased expression of the Ptgs2 gene and its corresponding COX-2 protein. Celecoxib, a selective COX-2 inhibitor, limited upregulation of Ptgs2 in BECs. In this study, we have defined the gene expression profiling of BECs after experimental SAH and provide further insight into BBB pathophysiology, which may be relevant to other neurological diseases such as traumatic brain injury, brain tumours, ischaemic stroke, multiple sclerosis, and neurodegenerative disorders.

Concurrent Prophylactic Mastectomy, Immediate Reconstruction, and Salpingo-Oophorectomy in High-Risk Patients: A Case Series.

PURPOSE: There are limited data on coordinated breast and gynecological risk-reduction surgery for high-risk patients in Canada. Therefore, this study aims to evaluate the patient demographics, surgical details, and outcomes of prophylactic mastectomy (PM) with immediate reconstruction and bilateral salpingo-oophorectomy (BSO) in high-risk patients. METHODS: We conducted a retrospective chart review at an academic center of patients who concurrently underwent PM with immediate reconstruction and laparoscopic BSO over a 7-year period (March 2010-February 2017) were identified. RESULTS: A total of 16 patients underwent PM with immediate reconstruction and concurrent BSO. The mean age at the time of surgery was 46.2 ± 6.6 years. Thirteen (81%) patients were carriers of the BRCA1 or BRCA2 mutation. Two patients had prophylactic surgical therapy for BRCA1 mutation and 14 (87.5%) patients had prior oncological treatment. The most common type of procedures performed were skin-sparing, nipple-sparing mastectomy (56.2%) and reconstruction with acellular dermal matrix and implants (43.8%). All patients underwent laparoscopic BSO. The average combined case time was 282.5 ± 81.3 minutes with an average postoperative hospital stay of 1.3 ± 0.5 days. Six (37.5%) patients presented with 30-day postoperative complications, with higher rates in the alloplastic group. There were no gynecological complications. CONCLUSIONS: In conclusion, our results demonstrate that a combined multidisciplinary surgical approach did not increase length of stay or 30-day complication rates. Furthermore, concurrent risk-reducing strategies are an effective option for patients at high risk of breast or ovarian cancer.

OBJECTIFS: Les données sur la coordination des opérations mammaire et gynécologique de réduction des risques sont limitées chez les patientes à haut risque au Canada. La présente étude vise donc à évaluer la démographie des patientes, les détails de l'opération et les résultats cliniques d'une mastectomie prophylactique (MP) suivie d'une reconstruction immédiate et d'une salpingoovariectomie bilatérale (SOB) chez des patientes à haut risque. MÉTHODOLOGIE: Dans un centre universitaire, les chercheurs ont réalisé une analyse rétrospective des dossiers des patientes qui ont subi une MP coordonnée avec une reconstruction immédiate et une SOB par laparoscopie, et ce, sur une période de sept ans (de mars 2010 à février 2017). RÉSULTATS: Au total, 16 patientes, d'un âge moyen de 46,2 ± 6,6 ans au moment de l'opération, ont subi une MP coordonnée avec une reconstruction immédiate et une SOB. Treize d'entre elles (81 %) étaient porteuses de la mutation du gène BRCA1 ou BRCA2. Deux patientes ont subi un traitement chirurgical prophylactique à cause de la mutation du gène BRCA1 et 14 patientes (87,5 %) avaient subi un traitement oncologique auparavant. Les interventions les plus pratiquées étaient une mastectomie avec conservation de la peau et des mamelons (56,2 %) et une reconstruction par implants avec matrice dermique acellulaire (43,8 %). Toutes les patientes ont subi une SOB par laparoscopie. Les cas combinés ont duré 282,5 ± 81,3 minutes en moyenne et ont été associés à une hospitalisation postopératoire moyenne de 1,3 ± 0,5 jour. Six patientes (37,5 %) ont souffert de complications dans les 30 jours suivant l'opération, et le taux était plus élevé dans le groupe alloplastique. Aucune complication gynécologique n'a été observée. CONCLUSIONS: Les résultats démontrent qu'une approche chirurgicale multidisciplinaire combinée n'ont accru ni la durée de l'hospitalisation ni le taux de complications au bout de 30 jours. De plus, les stratégies coordonnées de réduction du risque constituent une option efficace pour les patientes à haut risque de cancer du sein ou des ovaires.

Robust effects of genetic background on responses to subarachnoid hemorrhage in mice.

Outcome varies among patients with subarachnoid hemorrhage but known prognostic factors explain only a small portion of the variation in outcome. We hypothesized that individual genetic variations influence brain and vascular responses to subarachnoid hemorrhage and investigated this using inbred strains of mice.Subarachnoid hemorrhage was induced in seven inbred and a chromosome 7 substitution strain of mouse. Cerebral blood flow, vasospasm of the middle cerebral artery, and brain injury were assessed. After 48 h of subarachnoid hemorrhage, mice showed significant middle cerebral artery vasospasm that correlated positively with reduction in cerebral blood flow at 45 min. Mice also had increased neuronal injury compared to sham controls; A/J and C57BL/6 J strains represented the most and least severe, respectively. However, brain injury did not correlate with cerebral blood flow reduction at 45 min or with vasospasm at 48 h. Chromosome 7 substitution did not influence the degree of vasospasm or brain injury.Our data suggested that mouse genetic background influences outcome of subarachnoid hemorrhage. Investigations into the genetic factors causing these inter-strain differences may provide insight into the etiology of the brain damage following subarachnoid hemorrhage. These findings also have implications for animal modeling of disease and suggest that genetic differences may also modulate outcome in other cardiovascular diseases.

Experimental models of chronic subdural hematoma.

OBJECTIVES: Chronic subdural hematoma (CSDH) is a common neurosurgical problem. Most studies of pathogenesis and treatment involve humans. Advances in understanding of human diseases may be made using animal models. We reviewed all animal models of CSDH and report here their results, conclusions and limitations in order to set a baseline upon which further advanced experimental work related to this disease can be made. METHODS: PubMed, Medline, Embase and ISI Web of Knowledge were searched with no time limits using the keyword 'chronic subdural hematoma' and MeSH term 'hematoma, subdural, chronic'. The authors reviewed all papers written related to this disease and selected all publications involving animals. There were no other restrictions. The findings and conclusions of the papers are summarized here. No formal analysis was done because of the variation in species used, methods for induction of CSDH, times of assessment and reporting of results. RESULTS: Attempts to create CSDH have been made in mice, rats, cats, dogs and monkeys. Methods include injection or surgical implantation of clotted blood or various other blood products and mixtures into the potential subdural space or the subcutaneous space. No intracranial model produced a progressively expanding CSDH. Transient hematoma expansion with liquification could be produced by subcutaneous injections in some models. Spontaneous subdural blood collections were found after creation of hydrocephalus in mice by systemic injection of the neurotoxin, 6-aminonicotinamide. The histology of the hematoma membranes in several models resembles the appearance in humans. None of the models has been replicated since its first description. DISCUSSION: We did not find a report of a reproducible, well-described animal model of human CSDH.

Bilirubin and its oxidation products damage brain white matter.

Brain injury after intracerebral hemorrhage (ICH) occurs in cortex and white matter and may be mediated by blood breakdown products, including hemoglobin and heme. Effects of blood breakdown products, bilirubin and bilirubin oxidation products, have not been widely investigated in adult brain. Here, we first determined the effect of bilirubin and its oxidation products on the structure and function of white matter in vitro using brain slices. Subsequently, we determined whether these compounds have an effect on the structure and function of white matter in vivo. In all, 0.5 mmol/L bilirubin treatment significantly damaged both the function and the structure of myelinated axons but not the unmyelinated axons in brain slices. Toxicity of bilirubin in vitro was prevented by dimethyl sulfoxide. Bilirubin oxidation products (BOXes) may be responsible for the toxicity of bilirubin. In in vivo experiments, unmyelinated axons were found more susceptible to damage from bilirubin injection. These results suggest that unmyelinated axons may have a major role in white-matter damage in vivo. Since bilirubin and BOXes appear in a delayed manner after ICH, preventing their toxic effects may be worth investigating therapeutically. Dimethyl sulfoxide or its structurally related derivatives may have a potential therapeutic value at antagonizing axonal damage after hemorrhagic stroke.

Molecular alterations in the hippocampus after experimental subarachnoid hemorrhage.

Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.

Genetic elimination of eNOS reduces secondary complications of experimental subarachnoid hemorrhage.

Delayed complications of subarachnoid hemorrhage (SAH) such as angiographic vasospasm, cortical spreading ischemia, microcirculatory dysfunction, and microthrombosis are reported in both patients and animal models of SAH. We demonstrated previously that SAH is associated with increased oxidative stress in the brain parenchyma, and that this correlates with dysfunction of endothelial nitric oxide synthase (eNOS) (homodimeric uncoupling). Uncoupling of eNOS exacerbated oxidative stress and enhanced nitric oxide (NO) depletion, and was associated with multiple secondary complications such as microthrombosis, neuronal apoptosis, and release of reactive oxygen species. Thus, we hypothesized that genetic abbrogation of eNOS would confer a beneficial effect on the brain after SAH. Using a prechiasmatic injection model of SAH, we show here that eNOS knockout (KO) significantly alleviates vasospasm of the middle cerebral artery and reduces superoxide production. Endothelial nitric oxide synthase KO also affected other nitric oxide synthase isoforms. It significantly increases neuron nitric oxide synthase expression but has no effect on inducible nitric oxide synthase. Endothelial nitric oxide synthase KO decreases Zn(2+) release after SAH, reduces microthrombi formation, and prevent neuronal degeneration. This work is consistent with our findings where, after SAH, increased oxidative stress can uncouple eNOS via Zn(2+) thiolate oxidation, or theoretically by depletion or oxidation of tetrahydrobiopterin, resulting in a paradoxical release of superoxide anion radical, further exacerbating oxidative stress and microvascular damage.