London Health Sciences Centre Research Articles

Living with mild cognitive impairment

Mild Cognitive Impairment (MCI) refers to a decline in cognitive abilities which is greater than expected for normal aging but not severe enough to markedly interfere with a person's ability to manage their daily abilities. About 1 in 10 adults over the age of 65 years of age has MCI and recognizing MCI represents an opportunity for early intervention that could impact quality of life as well as prevent or delay the onset of dementia. In 2012 the Alzheimer Society London and Middlesex began facilitating a program to support individuals living with (MCI) entitled “Learning the Ropes.” This 6 week program, developed at Baycrest Hospital, aims to optimize cognitive health through lifestyle choices, memory training and psychosocial support. The content of this evidence based program includes formal instruction, interactive discussion and participation in training exercises. The program is delivered by Registered Social Workers at ASLM, tutored and trained by Dr. J. Fogarty, London Health Sciences Centre and Dr. Kelly Murphy, Baycrest Hospital. Since its inception 60 participants have completed the program, which includes the individual with a diagnosis of MCI and their family member or friend. The five ‘ROPES’ strategies are taught and emphasized throughout the 6 week session in addition to lifestyle and memory health education. As a result of the success of the MCI Program we have created an MCI Alumni Group to allow participants to obtain education and ongoing support. This group was in direct response to the participant's interest in continued opportunities to apply their new learning, to support one another and to obtain continued education on developments in the MCI community. Research shows that people with MCI can acquire new information and apply that learning to improve their performance on cognitive tasks and improvements in risk factors are associated with reduced dementia prevalence. Engaging in the Learning the Ropes program assists participants in making positive changes to promote their health and everyday memory to optimize their experience as a person living with MCI.

Incidence and natural history of intravenous immunoglobulin-induced aseptic meningitis: a retrospective review at a single tertiary care center.

Aseptic meningitis is a rare but significant complication of intravenous immunoglobulin (IVIG) therapy. The majority of literature is limited to case reports, so the true incidence of this complication is uncertain. A retrospective review of all cases of IVIG-associated adverse transfusion reactions was performed at London Health Sciences Centre (LHSC) from January 1, 2008, to December 31, 2013. All reported transfusion reactions were evaluated to identify cases of aseptic meningitis due to IVIG. All documented IVIG infusions and lumbar punctures performed during the study period were reviewed; patients with both interventions were identified and further chart review was performed to identify aseptic meningitis. During our study period, 1324 unique patients received a total of 11,907 IVIG infusions (554,566 g) for various conditions. Eight cases of aseptic meningitis were identified, suggesting an overall incidence of 0.60% for all patients and 0.067% for all IVIG infusions. Patients presented with symptoms within 24 to 48 hours of the infusion and were treated with antibiotics initially. The reactions were self-limited, as symptoms self-resolved within 5 to 7 days. Treatment was supportive, with subsequent IVIG infusions likely requiring preinfusion medication or possibly a switch in product formulation. This review of IVIG-induced aseptic meningitis over a 6-year period identifies a more robust estimate of incidence and risk of 0.60% and 0.067% for all patients and infusions, respectively. Given that this complication can mimic infectious meningitis and cause considerable morbidity, physicians need to be aware of this rare but important condition.

Effect of Day of the Week on Mortality and Cardiovascular Outcomes Following Elective AAA Repair and Lower Limb Revascularizations: A Population-Based Study

Effect of Day of the Week on Mortality and Cardiovascular Outcomes Following Elective AAA Repair and Lower Limb Revascularizations: A Population-Based Study Luc Dubois, Jennifer Winick-Ng, Andrew McClure, Kelly Vogt, Chris Vinden, Adam Power, Guy DeRose, Amit Garg. Western University, London, Ontario, Canada; Institute for Clinical Evaluative Sciences, London, Ontario, Canada; LHSC Victoria Hospital, London, Ontario, Canada; University of Western Ontario, London Health Science Centre, London, Ontario, Canada; Institure for Clinical Evaluative Sciences Western, London, Ontario, Canada

Intravenous Immunoglobulin (IVIg) Utilization in Immune Thrombocytopenia (ITP): A Multi-Center, Retrospective Review.

IntroductionIntravenous immunoglobulin (IVIg) is an immune thrombocytopenia (ITP) therapy, which is associated with toxicities, limited availability, increasing utilization, and high cost. This study aimed to assess short- and long-term IVIg utilization in patients with ITP at two tertiary care centers in Ontario, Canada, to determine the proportion of IVIg used in ITP compared with all usage, and to forecast IVIg demand in ITP.MethodsRecords from all adult ITP patients who received IVIg between January 1, 2003, and September 30, 2012, at Hamilton Health Sciences and London Health Sciences Centre were reviewed retrospectively.ResultsDuring the study period, 383 adult ITP patients (mean age 51.3 years) received a total of 2,098 IVIg infusions (London 547 infusions in 150 patients; Hamilton 1,551 infusions in 233 patients). ITP accounted for 5.6 and 9.1 % of all IVIg usage in London and Hamilton, respectively. The treatments included 264 (53.7 %) acute, 172 (35.0 %) short-term, and 56 (11.4 %) long-term treatments. The amounts of IVIg used for short- and long-term treatment of ITP are forecasted to be approximately 5,000 and 11,000 g per year, respectively, up to 2018. Together, these two centers represent 19.9 % of the provincial IVIg utilization. Assuming similar patient populations and practice patterns in Ontario, the overall provincial cost of IVIg use in ITP may be as high as $5 million annually.ConclusionShort- and long-term IVIg utilization for ITP will remain an expensive resource within the Ontario provincial health care system. Physicians and policy makers should reflect on the impact of treating ITP with IVIg and should consider alternatives, where appropriate, to improve patient quality of life and decrease economic costs.Electronic supplementary materialThe online version of this article (doi:10.1007/s40801-015-0009-6) contains supplementary material, which is available to authorized users.

Large retroperitoneal lymphadenopathy as a predictor of venous thromboembolism in patients with disseminated germ cell tumors treated with chemotherapy.

Cisplatin-based chemotherapy, a mainstay of treatment for disseminated germ cell tumors (GCTs), is associated with venous thromboembolism (VTE). Many patients with disseminated GCTs have large retroperitoneal lymph node (RPLN) metastases that may cause venous stasis and increase the risk of VTE development. We hypothesized that there was an association between large RPLN and chemotherapy-associated VTE risk. The training cohort was composed of patients with disseminated GCT receiving first-line chemotherapy at Princess Margaret Cancer Centre between January 2000 and December 2010. Large RPLN was defined as more than 5 cm in maximal axial diameter. The predictive and discriminatory accuracies of a model using large RPLN in predicting VTE were compared with high-risk Khorana score (≥ 3) using logistic regression and area under receiver operator characteristic curves (AUROCs). The model was externally validated in a cohort of patients treated at the London Health Sciences Centre. The training cohort comprised 216 patients, 21 (10%) of whom developed VTE during chemotherapy. VTE was associated with large RPLN (odds ratio [OR], 5.26; P = .001), high-risk Khorana score (OR, 11.8; P < .001), intermediate-/poor-risk disease (OR, 3.76; P = .005), and hospitalization during chemotherapy (OR, 4.24; P = .002). Large RPLN showed higher discriminatory accuracy than high-risk Khorana score (AUROC, 0.71 v 0.67, respectively). Superior discriminatory accuracy of large RPLN over high-risk Khorana score was validated in the London cohort (AUROC, 0.61 v 0.57, respectively). Large RPLN is associated with VTE in patients with disseminated GCT and provides higher discriminatory accuracy than high-risk Khorana score. Results should be validated in larger, prospective studies. Prophylactic anticoagulation may be considered in high-risk patients.

PTHrP-related Hypercalcaemia in Infancy and Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).

BackgroundSevere hypercalcaemia is a rare but clinically significant condition in infancy and childhood. Parathyroid hormone-related peptide (PTHrP)-mediated hypercalcaemia resulting from a malignancy is rare and only a handful of case reports have outlined its incidence alongside a benign condition.ObjectivesTo describe the diagnostic workup and management of an infant with hypercalcaemia, renal dysplasia, and elevated PTHrP levels.DesignCase report.SettingThe Victoria Hospital campus of the London Health Sciences Centre in London, Ontario, Canada.PatientsA child with congenital anomalies of the kidneys and urinary tract (CAKUT), stage 2 chronic kidney disease (CKD), and renal dysplasia who presented with severe hypercalcaemia.MeasurementsWeight, renal ultrasound, creatinine, cystatin C, eGFR, calcium, urea, bicarbonate, serum sodium, fractional sodium excretion, urine calcium to creatinine ratio, PTH, TSH, Free T4, AM cortisol, HMA, VMA, 25-vitamin D, 1,25 dihydroxy-vitamin D, calcitriol, vitamin A, ACE levels, skull and chest x-rays, alkaline phosphatase, CBC, tumour lysis profile, catecholamine breakdown, whole-body MRI, PTHrP.MethodsFull diagnostic workup and patient management. Patient treated with intravenous hydration, furosemide, calcitonin and CalciLo.ResultsPTHrP was elevated and no evidence of a malignancy was found. Treatment consisting of a low-calcium CalciLo diet (in place of breast milk) adequately controlled the patient’s hypercalcaemia. Hypercalcaemia associated with CAKUT in infancy is not all that uncommon and was reported in 15/99 infants in another study, most of whom had a suppressed PTH similar to that of our patient. PTHrP was not measured in these cases and may have also been elevated.LimitationsThe study is limited in that it is a description of a single patient case. Future measurement of PTHrP in similar patients is necessary to confirm our results.ConclusionsThe possibility of elevated PTHrP levels must be considered in patients with known renal dysplasia who are differentially diagnosed with hypercalcaemia.

Neurofibromatosis

Neurofibromatosis type 1 (NF1) is an inherited tumor predisposition syndrome with multiple manifestations in children and adults. Due to the multisystemic nature of this syndrome there are multidisciplinary NF1 clinics in many major centres in the United States; however, this is not yet the trend in Canada. Our study seeks to gain understanding of the current state of health surveillance in children with NF1 in Southwestern Ontario, which medical disciplines are involved in their care and parental interest in a future multidisciplinary clinic at London Health Sciences Centre (LHSC).&#x0D; Methods: 50 parents or guardians of pediatric NF1 patients completed a 39-question telephone interview pertaining to diagnosis, aspects of yearly screening and willingness to attend a multidisciplinary clinic. Responses were then compared to the current screening guidelines for the pediatric NF1 population as suggested by the American Academy of Pediatrics.&#x0D; Results: Only 56% of patients receive an annual neurological exam, while over 87% are having yearly blood pressure screens. 40% of patients cite their medical geneticist as the main coordinator of their care, while 12% cite no coordination of care. 48% of families travel more than 50 km to LHSC, with the majority visiting &gt;3 times per year. 96% of participants are interested in participating in a multidisciplinary clinic.&#x0D; Conclusions: The results obtained from this study support the development of a multidisciplinary NF1 clinic at LHSC.

Incidence and Natural History of Ivig-Induced Aseptic Meningitis: A Retrospective Review at a Single Tertiary Care Centre

Background: Aseptic meningitis is a rare and significant complication of intravenous immunoglobulin (IVIg) therapy. The true incidence is unknown as there are a number of case reports and few thorough reviews. Some have suggested the incidence being 0-1% with one reported exception of 11% in the literature. It is important to recognize this condition clinically, as it often mimics infectious meningitis. To determine the true incidence and natural history of IVIg-induced aseptic meningitis, we conducted a retrospective review and case series at a single tertiary care centre by two separate methods. For this study, IVIg-induced aseptic meningitis was defined as: headache with meningismus or a deterioration in mental status after receiving IVIg, with or without accompanying fever, nausea, vomiting, pharyngitis, photophobia, and/or diarrhea (as per the Transfusion Transmitted Injuries Surveillance System of the Public Health Agency of Canada). IVIg headaches alone were not included in our review.Method: We performed a retrospective review of all cases of IVIg-induced aseptic meningitis at London Health Sciences Centre (LHSC) from January 1, 2008 to December 31, 2013. During the study period, the initial method was to evaluate all reported transfusion reactions (as per the Transfusion Reaction Course [TRAC] system for reporting) to identify possible or probable aseptic meningitis due to IVIg. Subsequently, in our second method, we reviewed and cross-referenced all documented IVIg infusions and all lumbar punctures performed at LHSC during the study period. All patients with both IVIg infusions and lumber punctures were identified and further chart review was performed to determine if these patients had aseptic meningitis due to IVIg. We report on our identified cases of IVIg-induced aseptic meningitis, identify the true incidence, and speculate on the natural history of this condition.Results: During our study period, a total of 1921 IVIg infusions (554,566 g) were administered, with major indications being: chronic inflammatory demyelinating polyneuropathy (25.7%), primary immune deficiency (14.1%), other (primarily rheumatologic indications – 13.9%), multifocal motor neuropathy (10.4%), and adult immune thrombocytopenia (7.4%). 8 cases of aseptic meningitis were reported to the transfusion laboratory by the first method, with no additional cases identified by the second method, which gave us an overall incidence of 0.42%. Indications included: aplastic anemia (1/8), immune thrombocytopenia (3/8), chronic inflammatory demyelinating polyneuropathy (1/8), autoimmune hemolytic anemia (1/8), primary immune deficiency (1/8), and myasthenia gravis (1/8). As per our case series, IVIg-induced aseptic meningitis is an uncommon complication of unknown etiology that seems to affect all ages, with no relation to the underlying indication for IVIg. The only predisposing factor seen in our cohort may be a prior exposure to blood products, but other risk factors such as migraines, immune dysregulation, and dose and rate of infusion have been reported in the literature. In this study, patients presented with symptoms within 24-48 hours of IVIg infusion, and were treated with antibiotics initially due to the clinical resemblance and suspicion of bacterial meningitis. However, symptoms self-resolved within 5-7 days. This condition appears to be non-fatal; therefore, treatment is purely supportive, with subsequent IVIg infusions likely requiring premedication or possibly a switch in formulation.Conclusion: In this review of IVIg-induced aseptic meningitis over a 6 year period in a tertiary care centre, we identify a more robust incidence of 0.42% for this condition (consistent with most previous reports). Though this condition can be under-recognized, all possible cases were identified with a rigorous TRAC system for reporting reactions and by using two different methods. Furthermore, we speculate on the natural history of this condition based on our 8 identified cases. Given that this complication can mimic infectious meningitis and cause considerable morbidity, we hope that physicians will be aware of, and recognize, this rare but important complication of IVIg therapy. DisclosuresNo relevant conflicts of interest to declare.

Detection of Paroxysmal Nocturnal Hemoglobinuria Clones in Patients with Idiopathic Venous Thromboembolism

Background. Paroxsymal Nocturnal Hemoglobinuria (PNH) is an uncommon disease with an estimated population prevalence of 0.002%, however the estimated prevalence of venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) or pulmonary embolism (PE), in PNH patients is 25 to 33%. Small PNH clones have been identified in patients with unexplained splanchnic vein thrombosis and in people with apparently normal blood counts and might predispose these patients to thrombosis. Furthermore, only about 40-50% of idiopathic VTE patients are affected by one or more thrombophilias. The presence of PNH clones as a contributing factor to a hypercoagulable state has never been examined in this population.Patients and Methods. In order to determine the prevalence of PNH clones in patients with prevalent idiopathic DVT/PE we conducted a cross-sectional study at the Thrombosis Clinic of the London Health Sciences Centre in London, Ontario, Canada, between May 2011 and June 2014. We included patients with at least one episode of objectively demonstrated DVT or PE according to previously published criteria. Patients were excluded if they had: a) a previous diagnosis of PNH, b) well established predisposing risk factors for VTE in the 3 months preceding the VTE, c) active cancer other than non-melanoma skin cancer within 6 months of VTE, or if they were unable to provide written informed consent. Clinical and laboratory information was abstracted from the patient charts. Patients were screened for PNH using a high sensitivity flow cytometric assay which can detect at least 0.01% GPI deficient erythrocytes using CD235a and CD59 in a 2 color assay. Additionally, a modification of our previously developed fluorescent aerolysin (FLAER) assay was used to detect GPI deficient neutrophils using FLAER, the GPI linked protein CD24, CD45 and CD15 (a mature neutrophil marker) in a 4 color flow cytometric assay. A control group of 30 normal donors was used to standardize, determine and validate the level of sensitivity of both the red and white cell assays. The primary outcome of the study was the presence of a PNH clone >0.02% in erythrocytes or neutrophils. Secondary outcome was the presence a PNH clone of any size. Assuming an underlying PNH proportion in the population of 0.002%, we estimated that a sample size of 402 patients achieved 80% power to detect a proportion of 0.4%. Confidence intervals for proportions were calculated using the Wilson score method.ResultsWe included 394 patients of which 388 had samples available for flow cytometry. The characteristics of the included patients are shown in Table 1. One patient (0.26%; 95% CI 0.05 to 1.45) had a detectable PNH clone in the neutrophil population (0.02%) whereas another patient had a detectable PNH clone below the positivity threshold (<0.01%). Neither patient had evidence of hemolysis or cytopenias.ConclusionVery small PNH clones can be detected in a small proportion of patients with unexplained VTE but without clinical manifestations of hemolytic PNH. Their relation with the development of VTE is yet to be determined.Table 1Patients’ characteristicsDemographics [n/N (%; 95% CI)]Age (years) [Mean (SD)]57(16.6)Body Mass Index [Mean (SD)]31.5 (8.5)Male Gender216/388 (55.7;50.7-60.5)Caucasian ethnicity365/388 (94.1;91.3-96.0)Family History of VTE102/370 (27.6;23.3-32.3)Comorbidities [n/N (%; 95% CI)]Hypertension125/386 (32.4;27.9-37.2)Diabetes48/386 (12.4;9.5-16.1)Coronary artery disease33/381 (8.7;6.2-11.9)Stroke / TIA33/381 (8.7;6.2-11.9)Dyslipidemia104/340 (30.6;25.9-35.7)COPD22/380 (5.8;3.9-8.6)Peripheral vascular disease35/310 (11.3;8.2-15.3)Inflamatory bowel disease13/383 (3.4;2.0-5.7)Rheumatic disease100/362 (27.6;23.3-32.4)Risk factors for VTE [n/N (%; 95% CI)]Oral contraceptive use43/171 (25.1;19.2-32.1)Hormone replacement therapy14/171 (8.2;4.9-13.3)Thrombophilia127/388 (32.7;28.3-37.6)Diagnosis [n/N (%; 95% CI)]DVT175/388 (45.1;40.2-50.1)PE148/388 (38.1;33.4-43.1)DVT + PE63/388 (16.2;12.9-20.2)Upper extremity DVT2/388 (0.5;0.1-1.9)n, Number of patients with risk factor; N, number of patients with valid information;SD standard deviation; CI confidence interval DisclosuresLazo-Langner:Alexion Pharmaceuticals: Research Funding. Keeney:Alexion Pharmaceuticals: Research Funding. Chin-Yee:Alexion Pharmaceuticals: Research Funding.

Can we improve the morbidity and mortality associated with the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure in the management of colorectal liver metastases?

Meticulous selection of patients who can undergo the associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) procedure safely will be paramount to minimize the associated morbidity and mortality. We collected data prospectively on 14 consecutive patients who underwent the ALPPS procedure for planned resection of colorectal liver metastases at London Health Sciences Centre, Canada, between April 2012 and November 2013. The median relative increase of the standardized future liver remnant after the ALPPS procedure was 93 ± 28%. The standardized future liver remnant rate of volume increase was 35 ± 13 mL/day. Biopsies of the FLR were taken during stage 1 and 2. These biopsies showed a mean preregeneration Ki-67 index of 0% and a postregeneration index of 14 ± 3%. All 14 ALPPS patients completed the 2-stage hepatectomy. No complications occurred after ALPPS stage 1. After ALPPS stage 2, 5 patients had complications (36%), with 2 patients (14%) having a severe complication (Clavien-Dindo ≥ IIIB). Median follow-up was 9 months. Overall survival at the time of follow-up was 100%. Recurrence developed in 2 patients. One patient had recurrence in the liver and lungs 5 months after stage 2 and was offered more chemotherapy. The other patient developed recurrence in the liver remnant 9 months after stage 2 and underwent additional chemotherapy with a possible future resection of the recurrence. Low morbidity and negligible mortality can be achieved with the ALPPS procedure, and the high rates published in previous reports can be improved with refinements in technique and patient selection. The ALPPS approach may be a valid option to enable resection in selected patients with colorectal liver metastases considered unresectable previously by standard techniques.

PROSTHESIS-PATIENT MISMATCH IN VALVULAR HEART DISEASE: AN EVALUATION OF ECHOCARDIOGRAPHIC FINDINGS

Guidelines for reporting echocardiographic studies in prosthetic heart valve patients have recently been published. Prothesis-patient mismatch (PPM) was first described in 1978 and is present when the effective orifice area (EOA) of an implanted surgical prosthetic valve is too small in relation to a patient’s body surface area (BSA). PPM remains a common occurrence and has been reported in the literature in up to 20-70% of AVR patients. This is concerning, since undersized prostheses relative to body size may result in higher transprosthetic gradients, worse hemodynamic function and adverse patient outcomes. We examined reporting trends in patients with prosthetic aortic and mitral valves at London Health Sciences Centre (LHSC)and St Joseph's Health Care, with particular focus on PPM in these patient populations. Patients with prosthetic aortic valve replacement (AVR) and/or mitral valve replacement (MVR) undergoing echocardiography between September 2003 and August 2013 were identified. Studies with complete patient data for whom PPM could be measured were included for further analysis. PPM was defined as EOA/BSA ≤ 0.85 cm2/m2 in the aortic position (0.65-0.85 cm2/m2 moderate, <0.65 cm2/m2 severe), and as ≤ 1.3 cm2/m2 in the mitral position. Demographic and echocardiographic parameters were evaluated. Overall 8901 studies from 3378 patients were identified (61% male; mean age 68 ± 13 years). Echocardiographic studies (mean 2.6 studies/patient) were performed in patients with AVR (6290, 71%), MVR (1904, 21%) or both (707, 8%). Complete data sets were obtained for 2391 AVR studies. PPM was present in 44% of AVR studies (severe in 3%). AVR patients with PPM were older at the time of valve replacement (71 vs. 63 years) and at follow-up (73 vs. 65 years), had greater body weight (86 vs. 81kg), larger BSA (1.97 vs. 1.92kg/m2), smaller left ventricular dimensions (47 vs. 49mm), LVOT (19 vs. 20mm) and aortic roots (30 vs. 32mm), with higher transprosthetic gradients (34 vs. 26mmHg) and lower Doppler velocity index (0.41 vs. 0.44) in comparison to patients without PPM (p<0.001 for all). PPM was more common in females (48% vs. 41%, p=0.002), in those with bioprosthetic AVR (56% vs. 9%, p<0.001), with concurrent CABG (52% vs. 39%, p<0.001) and without concurrent aortic root enlargement surgery (46% vs. 32%, p<0.001). The presence of PPM in AVR patients in our study population was common. Our data analysis identified patient subsets with a higher prevalence of PPM, which co-localized with indices of impaired cardiac performance.

IMPACT OF A WHOLE BODY PERFUSION STRATEGY DURING CIRCULATORY ARREST FOR AORTIC ARCH RECONSTRUCTIVE SURGERY

During aortic arch reconstructive surgery, continuous coronary and antegrade cerebral perfusion (ACP) has been shown to provide optimal myocardial and cerebral protection. However, hypothermia alone without perfusion is frequently trusted for lower body protection. When prolonged, visceral and lower body ischemia can result in metabolic debt, leading to significant lactic acidosis and end organ dysfunction. Between January 2008 and April 2014 a single surgeon at London Health Sciences Centre performed 83 consecutive proximal aortic arch reconstructive surgeries requiring hypothermic circulatory arrest (HCA). All operations were performed using ACP and moderate hypothermia (21°C to 28°C). Forty-two patients had their surgery using only ACP and HCA. Forty-one patients had their surgery using a whole body perfusion (WBP) strategy (ACP, HCA, and additional lower body perfusion through femoral artery cannulation or direct descending aorta cannulation). Baseline characteristics, clinical outcomes, and metabolic data were analyzed. There were no significant differences in patient demographics or comorbidities between the 2 groups. The WBP group contained a significantly higher number of patients undergoing total arch reconstruction (56% versus 19%, p<0.01) with a concomitant need for significantly longer bypass time (268±79 versus 205±55 minutes, p<0.01), cross clamp time (203±60 versus 131±57 minutes, p<0.01), and HCA time (43±29 versus 30±15 minutes, p=0.01). Both groups contained a similar proportion of aortic dissections and emergent cases. Despite the complexity of surgeries performed in the WBP group, there was not a significant increase in intraoperative or postoperative peak lactate levels. Similarly, there were no differences in bicarbonate levels; however intra-operative pH values were significantly lower in the WBP group but recovered within hours of ICU admission (see figure). Use of platelets (39% versus 59%, p=0.06) and FFP (37% versus 69%, p<0.01) was less in the WBP group, as was ICU length of stay (mean 5 days versus 8 days p=0.01). There were no differences between the groups in terms of postoperative outcomes including death (4.9% versus 7.1%, p=0.67) and any of 10 major postoperative complications (27% versus 31%, p=0.68). Aortic arch reconstructive surgery can be safely performed using a WBP strategy that combines moderate HCA and ACP with additional lower body perfusion. The technique may reduce metabolic debt in more complex arch cases and may be contributory to a reduction in the use of blood products and ICU length of stay. Further study is warranted.

Variable expression of the forgotten oncogene E5 in HPV-positive oropharyngeal cancer

BackgroundThe role of the HPV E6/E7 oncogenes in head and neck squamous cell cancer (HNSCC) has been studied extensively, but the role of the viral E5 protein remains poorly understood. Studies in cervical cancer indicate that E5 increases epidermal growth factor receptor (EGFR) recycling to the cell surface and enhances growth factor signal transduction. ObjectiveThis study was designed to examine the relationship between HPV E5, EGFR, and survival in HPV-positive HNSCC. Study designA retrospective search of the London Health Sciences Centre pathology database was performed to identify oropharyngeal cancer samples. HPV E5 and EGFR expression was measured by reverse transcriptase real-time PCR. ResultsThe majority of oropharyngeal tumor samples (59/82, 72%) were HPV-16 positive. Among the HPV-positive tumors, highly variable E5 expression was detected from early polycistronic transcripts. Tumors with high E5 expression levels had significantly higher EGFR levels (p=0.03). High E5 levels were correlated with improved recurrence-free survival, but not overall survival (p=0.02 and 0.71, respectively), whereas high EGFR was strongly associated with decreased recurrence-free and overall survival (p<0.001 and 0.006 respectively). Multivariate analysis revealed E5 and EGFR to be the strongest predictors of recurrence-free survival (p<0.01). ConclusionsHPV E5-encoded transcripts are variably expressed in HPV-positive HNSCC and this is correlated with EGFR expression in HPV-positive OPC. However, E5 and EGFR independently predict recurrence-free survival in opposing manners. These findings require further validation to determine if E5 and EGFR are useful biomarkers to stratify treatment intensity for patients with HPV-positive HNSCC.

Management Issues During Pregnancy in Women With Bipolar Disorder

Back to table of contents Previous article Next article Communications and UpdatesFull AccessManagement Issues During Pregnancy in Women With Bipolar DisorderVerinder Sharma, M.B.B.S., and Christina Sommerdyk, M.Sc.Verinder SharmaSearch for more papers by this author, M.B.B.S., and Christina SommerdykSearch for more papers by this author, M.Sc.Published Online:1 Mar 2014https://doi.org/10.1176/appi.ajp.2014.13111493AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: We read with interest the article by Clark et al. (1) on lamotrigine dosing in pregnant patients with bipolar I disorder. The authors report on the use of lamotrigine in eight patients with bipolar disorder, six of whom received concomitant psychotropic drugs including four women who were taking antidepressant drugs. Dosage adjustments of lamotrigine were made in response to hypomanic, manic, or depressive symptoms. It is not clear whether the dosages of concomitant psychotropic drugs remained the same during pregnancy. Of the three women requiring a dosage increase to manage symptoms, two were also taking antidepressants that can increase the recurrence of bipolar mood episodes both during and after pregnancy (2). There are no data suggesting that monitoring serum levels with corresponding adjustments to lamotrigine dosing will protect against antidepressant-led mood instability. Interestingly, the authors did not report a correlation between lamotrigine concentration and scores on rating scales for depression and mania. Thus, the conclusion that women with bipolar disorder who are treated with lamotrigine experience an increase in symptoms as a result of declining concentrations of this drug is not justified.While lamotrigine has a role in the management of bipolar disorder during pregnancy, no data on its effectiveness in the prevention of postpartum mood episodes are currently available. Moreover, lamotrigine is generally not recommended for the acute treatment of mania (3).Finally, the statement that pregnancy is a vulnerable period for recurrence of mood episodes is true for women treated at tertiary care centers with complex and often comorbid disorders and women who discontinue mood-stabilizing drugs. However, evidence from studies using nonclinical samples, retrospective studies, and studies on psychiatric hospitalization rates is suggestive of a positive effect of pregnancy on bipolar disorder (4).From the Departments of Psychiatry and Obstetrics & Gynecology, University of Western Ontario, London, Ontario, Canada; the Perinatal Clinic, London Health Sciences Centre, London, Ontario; and Regional Mental Health Care, London, Ontario.Professor Sharma has received grant support from, participated on scientific advisory boards for, or served on the speakers’ bureaus of AstraZeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, Janssen, Lundbeck, the Ontario Mental Health Foundation, Pfizer, Servier, and the Stanley Foundation. Ms. Sommerdyk reports no financial relationships with commercial interests.References1 Clark CT, Klein AM, Perel JM, Helsel J, Wisner KL: Lamotrigine dosing for pregnant patients with bipolar disorder. Am J Psychiatry 2013; 170:1240–1247Link, Google Scholar2 Viguera AC, Whitfield T, Baldessarini RJ, Newport DJ, Stowe Z, Reminick A, Zurick A, Cohen LS: Risk of recurrence in women with bipolar disorder during pregnancy: prospective study of mood stabilizer discontinuation. Am J Psychiatry 2007; 164:1817–1824Link, Google Scholar3 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O’Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M: Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013. Bipolar Disord 2013; 15:1–44Crossref, Medline, Google Scholar4 Sharma V, Pope CJ: Pregnancy and bipolar disorder: a systematic review. J Clin Psychiatry 2012; 73:1447–1455Crossref, Medline, Google Scholar FiguresReferencesCited byDetailsCited byRisk of Medication Exposures in Pregnancy and Lactation26 May 2021 Volume 171Issue 3 March 2014Pages 370-371 Metrics PDF download History Accepted 1 January 2014 Published online 1 March 2014 Published in print 1 March 2014

Childhood-onset nonprogressive chronic encephalitis

PurposeThe purpose of this study was to describe a series of patients with pathologically proven chronic encephalitis who had a nonprogressive course during a long follow-up, suggestive of a “benign” variant of Rasmussen's encephalitis (RE). MethodsFour patients who were referred to our Comprehensive Epilepsy Program at London Health Science Centre in London, Ontario, were diagnosed with chronic encephalitis on a pathological basis after epilepsy surgery to treat their partial-onset seizures. ResultsNone of our four cases followed the typical course of RE despite their childhood-onset seizures between ages 2 and 12years. One was preceded by a mild head trauma and fever at onset. None had epilepsia partialis continua (EPC). Their long-term follow-up revealed a nonprogressive form of the syndrome with respect to the neurological examination, EEG, MRI, and neuropsychological findings. ConclusionThese cases extend the spectrum of childhood-onset intractable epilepsy with chronic encephalitis to include nonprogressive variants of RE. The absence of EPC may be a prognostic indicator of a nonprogressive course.

Analgesia in the management of paediatric and adolescent trauma during the resuscitative phase: The role of the pediatric trauma centre

BackgroundThe objective of this study was to evaluate the use of analgesia in the resuscitative phase of severely injured children and adolescents. MethodsA retrospective cohort of paediatric (age<18 years), severely injured (ISS≥12) patients were identified from the London Health Sciences Centre's Trauma Registry from 2007 to 2010. Variables were compared between Analgesia and Non-analgesia groups with Pearson Chi-square and Mann–Whitney U tests. Resuscitative analgesia use was assessed through multivariable logistic regression controlling for age, gender, mechanism, arrival and Trauma Team Activation (TTA). ResultsAnalgesia was used in 32% of cases. Univariate analysis did not reveal any differences in gender, age, injury type, injury profile and arrival patterns. Significant differences were found with analgesia used more frequently in patients injured in a motor vehicle collision (58% vs. 42%, p=0.026) and having parents in the resuscitation room (17% vs. 6%, p=0.01). Analgesia patients were more injured (median ISS 22 vs. 17, p=0.027) and had 2.25 times more TTA (39% vs. 17%). Logistic regression revealed patients arriving directly to a trauma centre had a higher incidence of receiving analgesia (OR 2.01, 95% CI: 1.03–3.93), as did TTA (OR 2.18, 95% CI: 1.01–4.73) and having parents in resuscitation room (3.56, 95% CI: 1.23–10.33). Narcotics were most commonly used (85%), followed by benzodiazepines (16%), with 66% given during the primary survey. ConclusionUse of analgesia is important in the acute management of paediatric trauma. Direct presentation to a level I trauma centre, TTA and the presence of parents lead to higher appropriate use of analgesia in paediatric trauma resuscitation.

Prognosis of delirium in hospitalized elderly: worse than we thought

Despite treatment of the associated condition, delirious persons do not always recover for unknown reasons. We sought to determine early prognostic indicators of poor recovery following an episode of delirium in older medical in-patients. Between October 2009 and July 2011, consecutively admitted older (≥70 years old) medical in-patients at the London Health Sciences Centre (Ontario) were screened for delirium. Delirious patients were followed. The primary outcome was poor recovery, in delirious patients, defined by death, long-term institutionalization, or functional decline (decreased activities of daily living), at discharge or 3 months after discharge, elicited from the medical chart or post-discharge caregiver telephone interviews. One thousand two hundred thirty-five in-patients (mean age 82.6 years, 42% men) were screened, delirium occurred in 355 (29%). Follow-up data was known on 342 (96%), and 237 (69%) had poor recovery: 55 died (54 in hospital and one after discharge), 136 were permanently institutionalized (86 directly from hospital and 50 after discharge), and 46 had functional decline (at a median of 103 days after discharge). Poor recovery was associated in the derivation sample with advanced age, lower baseline function, hypoxia, higher delirium severity scores, and acute renal failure; this was predictive of poor recovery in the validation sample (receiver operating characteristic area 0.68, 95% confidence interval: 0.57-0.79); however, even individuals with "low" risk had high (50%) poor recovery rates. Poor recovery after delirium is common and associated with certain characteristics. However, even "lower risk" delirious individuals do poorly. More research is needed to understand prognostic factors in delirium.

Endolymphatic Sac Surgery Versus Intratympanic Gentamicin for the Treatment of Intractable Ménière’s Disease

1) To review a 10-year experience of endolymphatic sac surgery (ESS) and intratympanic gentamicin (ITG) for intractable Ménière's disease (MD), and 2) to compare preoperative and postoperative outcomes. Retrospective chart review and survey. Tertiary care center. Patients treated with ESS or ITG between 1997 and 2007 at London Health Sciences Centre were eligible for recruitment. ESS or ITG. 1) 1995 American Academy of Otolaryngology-Head and Neck Surgery hearing stage, vertigo class, and functional level; and 2) a 40-item validated quality-of-life questionnaire (MD Outcome Questionnaire). Chi-squared and t tests. Sixty-seven patients were recruited (n = 30 ESS; n = 37 ITG). Preoperatively, the ITG group had poorer hearing stage (p = 0.03). There were no differences between groups on preoperative functional level and QOL measures. Postoperatively, ESS patients reported more tinnitus (p = 0.003) and aural fullness (p = 0.01). There were no differences in posttreatment vertigo class. Secondary treatment was required for 27% of patients in the ESS compared with 3% in the ITG. Posttreatment hearing remained unchanged for the ITG and was overall decreased in the ESS group (p = 0.03). Participants in the ITG reported better postoperative functional levels (p = 0.02) and higher global (p = 0.04), social (p = 0.001), and overall QOL scores (p = 0.03). ITG, compared with ESS, reveals better posttreatment functional levels, and superior global, social, and overall QOL scores. Although no statistical difference in vertigo class, a clinical difference is observed.

Socioeconomic and Geographic Disparities in Access to Endovascular Abdominal Aortic Aneurysm Repair

Within Southwestern Ontario, abdominal aortic aneurysm (AAA) surgery has been centralized to a single university-affiliated medical center. The referral area serves 1.9 million people and includes community hospitals with limited vascular surgery capabilities. We reviewed the role of patients' travel distance, geographic location, and socioeconomic status (SES) to determine if centralization of endovascular programs results in disparity in access to endovascular surgery. We hypothesized that patients would travel a longer distance to specifically seek elective endovascular surgery while having open and emergent surgery closer to home. All patients who underwent AAA repair (July 2005-June 2010) at London Health Science Centre were identified from the vascular surgery database. Method of repair, clinical presentation, and in-hospital mortality were recorded. Travel distance from each patient's home to our hospital and rural versus urban status was determined for each patient. SES was determined by using a previously validated, locally developed deprivation index. During this 5-year period, 1,243 patients were included in our analysis; 46.8% (n=581) underwent endovascular repair (EVAR) and 53.2% (n=662) underwent open repair. For elective cases, the in-hospital mortality rate was 2.0% (n=11) for EVAR and 3.6% (n=20) for open repair (P=0.1). There was no difference in clinical presentation between SES groups, but open repair was more frequently used in patients of lower SES compared to higher SES (odds ratio=1.32; 95% confidence interval: 1.02-1.72). Travel distance and rural/urban status were not associated with increased odds of EVAR. When ruptured aneurysms were excluded, elective patients of lower SES continued to have a higher rate of open surgery. Despite the centralization of endovascular programs in Canada, patients do not appear to be traveling a longer distance for EVAR while having open repairs closer to home as we expected. We did note that higher SES was associated with increased odds of EVAR, which may suggest a health care access bias for EVAR for patients of higher SES. Larger, population-based studies at the provincial or national level could confirm these initial findings.

Fournier’s gangrene of the penis caused by Streptococcus dysgalactiae subspecies equisimilis: case report and incidence study in a tertiary-care hospital

BackgroundFournier’s gangrene is a rare necrotizing soft tissue infection of the scrotum and penis. We report, to our knowledge, the first case of Fournier’s gangrene caused by Streptococcus dysgalactiae subsp. equisimilis (SDSE), a strain of pyogenic β-hemolytic streptococci that is increasingly being recognized as an important human pathogen.Case presentationWe describe a healthy 59 year-old Caucasian male who presented to the emergency department with Fournier’s gangrene of the penis and scrotum, with extension to the anterior abdominal wall. He underwent urgent surgical debridement of his scrotum, penis, and anterior abdomen. Swabs from the scrotum grew Gram-positive cocci, which were initially identified as Streptococcus anginosus group by matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). However, polymerase chain reaction (PCR) amplification and sequencing of the 16S rRNA gene identified the isolate as Streptococcus dysgalatiae subspecies equisimilis (SDSE). The incidences of invasive S. anginosus group and SDSE infections at the London Health Sciences Centre, a tertiary-care institution in southwestern Ontario, were determined between August 1, 2011 and August 31, 2012, revealing a slightly lower rate of SDSE (3.2 cases per 100,000 population) than other studies.ConclusionsThis case highlights a unique disease manifestation of the emerging human pathogen Streptococcus dysgalatiae subspecies equisimilis that has not been previously reported. This case also underscores the limitations of MALDI-TOF MS in differentiating between closely-related streptococcal species which may have different pathogenic profiles.