Bilateral external iliac vein compression-An important consideration in implantation of leadless permanent pacemaker.

We report on an unusual case with asymptomatic bilateral external iliac vein non-thrombotic obstruction causing difficulty in delivery of the leadless permanent pacemaker and discuss on the strategies to overcome the problem.

Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized Trial.

BACKGROUND: The Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clinically measurable benefit with respect to risk of mortality or early complications with early dialysis initiation versus deferred dialysis start. After these findings, guidelines recommended an intent-to-defer approach to dialysis initiation, with the goal of deferring it until clinical symptoms arise. METHODS: To evaluate a four-component knowledge translation intervention aimed at promoting an intent-to-defer strategy for dialysis initiation, we conducted a cluster randomized trial in Canada between October 2014 and November 2015. We randomized 55 clinics, 27 to the intervention group and 28 to the control group. The educational intervention, using knowledge-translation tools, included telephone surveys from a knowledge-translation broker, a 1-year center-specific audit with feedback, delivery of a guidelines package, and an academic detailing visit. Participants included adults who had at least 3 months of predialysis care and who started dialysis in the first year after the intervention. The primary efficacy outcome was the proportion of patients who initiated dialysis early (at eGFR >10.5 ml/min per 1.73 m2). The secondary outcome was the proportion of patients who initiated in the acute inpatient setting. RESULTS: The analysis included 3424 patients initiating dialysis in the 1-year follow-up period. Of these, 509 of 1592 (32.0%) in the intervention arm and 605 of 1832 (33.0%) in the control arm started dialysis early. There was no difference in the proportion of individuals initiating dialysis early or in the proportion of individuals initiating dialysis as an acute inpatient. CONCLUSIONS: A multifaceted knowledge translation intervention failed to reduce the proportion of early dialysis starts in patients with CKD followed in multidisciplinary clinics. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov, NCT02183987. Available at: https://clinicaltrials.gov/ct2/show/NCT02183987.

Association Between the Publication of the Initiating Dialysis Early and Late Trial and the Timing of Dialysis Initiation in Canada.

Importance: Published in 2010, the Initiating Dialysis Early and Late (IDEAL) randomized clinical trial, which randomized patients with an estimated glomerular filtration rate (GFR) between 10 and 15 mL/min/1.73 m2 to planned initiation of dialysis with an estimated GFR between 10 and 14 mL/min/1.73 m2 (early start) or an estimated GFR between 5 and 7 mL/min/1.73 m2 (late start), concluded that early initiation was not associated with improved survival or clinical outcomes. Objective: To assess the association between the IDEAL trial results and the proportion of early dialysis starts over time. Design, Setting, and Participants: This interrupted time series analysis used data from the Canadian Organ Replacement Register to study adult (≥18 years of age) patients with incident chronic dialysis between January 1, 2006, and December 31, 2015, in Canada, which has a universal health care system. Patients from the province of Quebec were excluded because its privacy laws preclude submission of deidentified data without first-person consent. The patients included in the study (n = 28 468) had at least 90 days of nephrologist care before starting dialysis and a recorded estimated GFR at dialysis initiation. Data analyses were performed from November 2016 to January 2019. Main Outcomes and Measures: The primary outcome was the proportion of early dialysis starts (estimated GFR >10.5 mL/min/1.73 m2), and the secondary outcomes included the proportions of acute inpatient dialysis starts, patients who started dialysis using a home modality, and patients receiving hemodialysis who started with an arteriovenous access. Measures included the trend prior to the IDEAL trial publication, the change in this trend after publication, and the immediate consequence of publication. Results: The final cohort comprised 28 468 patients, of whom 17 342 (60.9%) were male and the mean (SD) age was 64.8 (14.6) years. Before the IDEAL trial, a statistically significant increasing trend was observed in the monthly proportion of early dialysis starts (adjusted rate ratio, 1.002; 95% CI, 1.001-1.004; P = .004). After the IDEAL trial, an immediate decrease was observed in the proportion of early dialysis starts (rate ratio, 0.874; 95% CI, 0.818-0.933; P < .001), along with a statistically significant change in trend between the pretrial and posttrial periods (rate ratio, 0.994; 95% CI, 0.992-0.996; P < .001). No statistically significant differences were found in acute inpatient dialysis initiations, the proportion of patients receiving home dialysis as the initial modality, or the proportion of arteriovenous access creation at hemodialysis initiation after the IDEAL trial publication. Conclusions and Relevance: The publication of the IDEAL trial appeared to be associated with an immediate and meaningful change in the timing of dialysis initiation in Canada.

Knowledge Translation Interventions to Improve the Timing of Dialysis Initiation: Protocol for a Cluster Randomized Trial.

BACKGROUND: Early initiation of chronic dialysis (starting dialysis with higher vs lower kidney function) has risen rapidly in the past 2 decades in Canada and internationally, despite absence of established health benefits and higher costs. In 2014, a Canadian guideline on the timing of dialysis initiation, recommending an intent-to-defer approach, was published. OBJECTIVE: The objective of this study is to evaluate the efficacy and safety of a knowledge translation intervention to promote the intent-to-defer approach in clinical practice. DESIGN: This study is a multicenter, 2-arm parallel, cluster randomized trial. SETTING: The study involves 55 advanced chronic kidney disease clinics across Canada. PATIENTS: Patients older than 18 years who are managed by nephrologists for more than 3 months, and initiate dialysis in the follow-up period are included in the study. MEASUREMENTS: Outcomes will be measured at the patient-level and enumerated within a cluster. Data on characteristics of each dialysis start will be determined by linkages with the Canadian Organ Replacement Register. Primary outcomes include the proportion of patients who start dialysis early with an estimated glomerular filtration rate greater than 10.5 mL/min/1.73 m2 and start dialysis in hospital as inpatients or in an emergency room setting. Secondary outcomes include the rate of change in early dialysis starts; rates of hospitalizations, deaths, and cost of predialysis care (wherever available); quarterly proportion of new starts; and acceptability of the knowledge translation materials. METHODS: We randomized 55 multidisciplinary chronic disease clinics (clusters) in Canada to receive either an active knowledge translation intervention or no intervention for the uptake of the guideline on the timing of dialysis initiation. The active knowledge translation intervention consists of audit and feedback as well as patient- and provider-directed educational tools delivered at a comprehensive in-person medical detailing visit. Control clinics are only exposed to guideline release without active dissemination. We hypothesize that the clinics randomized to the intervention group will have a lower proportion of early dialysis starts. LIMITATIONS: Limitations include passive dissemination of the guideline through publication, and lead-time and survivor bias, which favors delayed dialysis initiation. CONCLUSIONS: If successful, this active knowledge translation intervention will reduce early dialysis starts, lead to health and economic benefits, and provide a successful framework for evaluating and disseminating future guidelines. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02183987.

MISE EN CONTEXTE: Malgré l'absence d'avantages probants pour la santé des patients et en dépit de coûts plus élevés liés à la dialyse, la décision d'amorcer un tel traitement au moment où la fonction rénale du patient est encore relativement élevée (dialyse hâtive) est en forte hausse depuis une vingtaine d'années au Canada et partout dans le monde. Toutefois, les lignes directrices canadiennes publiées en 2014 à ce sujet recommandent plutôt de retarder le démarrage de la dialyse. OBJECTIFS DE L'ÉTUDE: Cette étude a pour but d'évaluer l'efficacité et la sécurité d'une intervention au niveau de l'application des connaissances qui favoriserait le démarrage tardif de la dialyse chronique dans la pratique. CADRE ET TYPE D'ÉTUDE: Il s'agit d'un essai clinique randomisé en deux groupes parallèles avec échantillonnage par grappes (clusters). Cinquante-cinq cliniques multidisciplinaires traitant des patients en insuffisance rénale chronique et provenant de partout au Canada participent à l'étude. PATIENTS: L'étude porte sur des patients adultes suivis par un néphrologue depuis plus de trois mois et ayant démarré la dialyse au cours de la période de suivi. MESURES: Les données recueillies seront mesurées au niveau des patients et analysées par regroupement (clusters). Les paramètres de démarrage pour chaque début de dialyse seront établis par la consultation du registre canadien des insuffisances et des transplantations d'organes (RCITO). Les issues primaires sont i) la proportion de patients qui auront démarré la dialyse avec un débit de filtration glomérulaire estimé de plus de 10,5 mL/min/1,73 m2 (dialyse hâtive); ii) la proportion de patients pour lesquels l'amorce aura été faite au cours d'une hospitalisation ou lors d'une admission aux urgences. Les issues secondaires qui seront mesurées incluent : le taux de variation dans le moment du démarrage de la dialyse, le taux d'hospitalisations, le nombre de décès et les coûts associés aux soins prédialyse (lorsque l'évaluation est possible). On voudra également établir un rapport trimestriel des nouveaux cas de démarrages de dialyses, et savoir à quel point les éléments de transmission des connaissances seront acceptés dans la pratique. MÉTHODOLOGIE: Nous avons randomisé 55 cliniques multidisciplinaires en traitement de l'insuffisance rénale (clusters) au Canada à recevoir, ou non, une intervention de transmission des connaissances portant sur les lignes directrices Canadiennes du démarrage de la dialyse. L'intervention consiste en une visite médicale individuelle où l'information pertinente et des outils pédagogiques, tant pour le patient que pour le médecin traitant, sont distribués. Le suivi est assuré par rétroaction et par des vérifications ponctuelles (audits). Les groupes contrôles sont quant à eux mis au fait des nouvelles recommandations sans toutefois recevoir d'outils pédagogiques ni être soumis à la diffusion active de l'information. Nous émettons l'hypothèse que la proportion de dialyses hâtives diminuera au sein des cliniques ayant été randomisées dans le groupe où une intervention sera effectuée. LIMITES DE L'ÉTUDE: La première limite consiste en la possible diffusion passive des nouvelles lignes directrices uniquement par voie de publication. En outre, les biais liés à la survie et au délai d'exécution favorisent les démarrages tardifs de dialyse. CONCLUSION: Une intervention réussie au niveau de la transmission des connaissances contribuera à réduire le nombre d'amorces de dialyse hâtives. Dès lors, on peut penser que cela aura une incidence sur les coûts reliés à cette procédure et des avantages pour la santé des patients. Enfin, cette étude pourrait constituer un cadre favorable pour procéder à l'évaluation et à la diffusion de futures lignes directrices.

A spuriously 'normal' haemoglobin A1c result.

We report a case of spuriously 'normal' haemoglobin A1c (HbA1c) result due to misidentification of HbG Taipei as HbAo by the Variant II built-in retention time algorithm. The defect was circumvented effectively by the implementation of a chromatographic system specific internal quality control mechanism for peak identity verification. HbA1c and estimated average glucose results were corrected from 4.7% to 8.2%, and 4.9 to 10.5 mmol/L, respectively. The results were consistent with the patient's concurrent and previous fasting blood glucose concentrations and existence of diabetes mellitus dermopathy, indicating poor glycaemic control. A review of currently available analytical systems showed that other than mass spectrometry, HbA1c measurements by these systems were generally affected by the presence of haemoglobin variants. The same haemoglobin variant may affect different analytical systems differently, resulting in the deviation of HbA1c results from the true value to different extents. Including the analytical principle of HbA1c measurement in the laboratory report can avoid inappropriate comparison of results obtained by different analytical systems. Moreover, since individual haemoglobinopathy may affect the degree of glucose binding to haemoglobin in a different way, this uncertainty limits the general application of same decision cut-off of established guidelines for glycaemic control monitoring. Adoption of an individualized monitoring system based on the critical difference or reference change value of HbA1c can be considered.

Recent developments in immune activation by uric acid crystals.

Uric acid crystals, the causative agent of gout, have recently gained widespread attention due to their role as a natural endogenous adjuvant. Uric acid crystals, first sensed extracellularly by membrane lipid alterations, are internalized and subsequently activate the NLRP3 inflammasome. Currently, various aspects of this particular novel pathway are poorly defined. This short review will focus on some recent discoveries regarding this simple crystalline structure and address areas requiring further investigation. The fact that uric acid crystals activate innate host defense mechanisms, triggering robust inflammation and immune activation, may lead to engineering potent adjuvants for future vaccines. Furthermore, the elucidation of uric acid's mechanism of inflammation may lay the foundation for other solid inflammatory structures such as silica, asbestos, and alum.

Isolated left ventricular non-compaction: an unusual indication for heart transplantation.

We report a patient with isolated left ventricular non-compaction diagnosed by echocardiography and cardiac magnetic resonance imaging. She developed refractory congestive heart failure and subsequently underwent successful heart transplantation. This type of cardiomyopathy is thought to be caused by the arrest of normal embryogenesis of the endocardium and myocardium. The spectrum of clinical, radiological, and pathological abnormalities is discussed.

Adenosine primes resting stage dendritic cells before their activation.

The effect of adenosine mediated suppression of immune cell activation has long been an important topic of study. While the protective benefits of such a signaling mechanism are well recognized, there remains a question as to how dendritic cells (DCs) bypass the high levels of adenosine during tissue stress and infection, and become fully activated. We report here that adenosine receptors on resting stage DCs, both in vivo and in vitro, are functionally desensitized after ligand binding. This desensitization lasts several hours during which DCs are "blind" to adenosine and are stimulated without this negative feedback. This effect is mediated by cAMP signaling. Our report suggests that there is a specific regulatory mechanism used by DCs to overcome adenosine mediated inhibition to become fully activated despite a general suppressive state.

Spontaneous atraumatic rupture of a normal-sized spleen due to AL amyloid angiopathy.

We report an unusual cause of hemoperitoneum in an AL amyloid patient on peritoneal dialysis due to spontaneous rupture of a normal-sized spleen not related to any trauma. The rupture was not due to amyloid deposition within the spleen pulp but rather due to amyloid angiopathy causing hemorrhage within the spleen and capsular tear.

Cardiac amyloidosis - experience in a tertiary cardiac referral centre.

Amyloidosis is an uncommon systemic disease characterized by deposition of insoluble fibrillar protein in different organs and the prognosis is poor if the heart is involved. Experience with management of cardiac amyloidosis is difficult because of its rare occurrence, late presentation and ineffective treatment. Since 1995, we have encountered and prospectively followed up 16 cases of cardiac amyloidosis in our cardiac centre. We believe this is the largest series of cardiac amyloidosis reported in Chinese patients. The 1-year, 3-year and 5-year survival rates were 40%, 25% and 17%, respectively. The major cause of death was cardiac-related. Those patients with overt heart failure or with untreated amyloidosis had a dismal prognosis (mean survival of 2.2 months and 3.5 months, respectively). Those who received specific treatment for the underlying amyloidosis had a better outcome with an average survival of 33.4 months.

Atrial septal defect with ascites and pleural effusion.

A case of a lady referred for repair of an atrial septal defect is described. She presented with an insidious onset of recurrent ascites and pleural effusion. Cardiac catheterization showed constrictive physiology. The patient subsequently underwent surgical closure of the atrial septal defect and pericardiectomy.

Aortitis.

Inflammatory or noninfectious aortitis may be idiopathic or it may be part of a systemic autoimmune disease, such as Takayasu's arteritis, Behçet's disease, or giant cell arteritis. At the acute stage, there is thickening of the aortic wall with dilatation of the aorta, more commonly in the thoracic aorta. If it involves the aortic root, there may be annuloaortic ectasia or aortic regurgitation. At a later stage, there may be aneurysmal dilatation of the aorta and rarely dissection or rupture of the aorta. In Takayasu's arteritis, stenosing lesions can occur as well as aneurysmal dilatation of the aorta or arteries. Stenosing lesions may be treated with angioplasty with or without stenting, whereas aneurysmal dilatation of the aorta is treated by aneurys-mectomy with arterial reconstruction or conduit. Severe aortic regurgitation may require aortic valve surgery with or without replacement of the ascending aorta. Irrespective of the interventional procedure undertaken as appropriate for the lesion, control of inflammation with steroid therapy with or without other immunosuppressive agents is of paramount importance. Otherwise, prosthetic valve or graft dehiscence may occur after aortic surgery, and restenosis rate is also higher after percutaneous transluminal angioplasty or stenting.

Effects of chronic sildenafil in patients with Eisenmenger syndrome versus idiopathic pulmonary arterial hypertension.

BACKGROUND: To test the hypothesis that chronic sildenafil treatment has similar functional and hemodynamic effects in patients with severe pulmonary arterial hypertension due to Eisenmenger syndrome as those due to idiopathic pulmonary arterial hypertension without intracardiac shunts. METHODS: A prospective open-label study was carried out to compare the effects of sildenafil on the pulmonary hemodynamics between two groups of patients with severe pulmonary hypertension and similar baseline functional capacity--Eisenmenger syndrome (ES group) (n=7) versus idiopathic pulmonary arterial hypertension (IPAH group) (n=6). RESULTS: After 6 months of sildenafil, there was a significant improvement in the functional capacity, the arterial saturation and the pulmonary hemodynamics in the ES group, as shown by significant reduction in the systolic and mean pulmonary artery pressures and the pulmonary vascular resistance. CONCLUSION: Sildenafil increases pulmonary blood flow and improves cyanosis in patients with Eisenmenger syndrome. Efficacy of sildenafil as treatment for idiopathic pulmonary arterial hypertension may be extended to patients with Eisenmenger syndrome.

Stability of green fluorescent protein (GFP) in chlorine solutions of varying pH.

Green fluorescent protein (GFP) is an excellent biosensor as a result of its ability to be easily monitored in a wide variety of applications. Enzymes and proteins have been used as biological indicators to evaluate the immediate efficacy of industrial procedures, such as blanching, pasteurization, and disinfection treatments, as well as to monitor the satisfactory preservation of a product subjected to disinfection or sterilization. The purpose of this work was to study GFP stability in chlorinated water for injection (WFI) and chlorinated buffered solutions at various pH ranges, with and without agitation, to evaluate the exposure time required for chlorine to decrease 90% of its fluorescence intensity (decimal reduction time, D-value, min, 25 degrees C). Fluorescence intensity (Ex/Emmax = 394/509 nm) was measured immediately after the addition of GFP (8.0-9.0 microg/mL) into buffered or unbuffered chlorine solutions with or without constant stirring. With solutions constantly stirred, GFP fluorescence decreased abruptly on contact with chlorine in concentrations greater than 150 ppm, with D-values between 1.3 min (147 ppm chlorine) and 1.7 min (183 ppm chlorine). In phosphate buffered chlorine solutions (pH = 7.15 +/- 0.08), GFP retained its structure between 52 and 94 ppm, but protein stability decreased 10-fold when exposed to 110 ppm chlorine. The recovery of GFP fluorescence intensity due to renaturation was observed between 30 and 100 ppm chlorine in WFI (final pH = 11.01 +/- 0.23) without stirring. Stirring enhanced the contact between GFP and chlorine throughout the assay and provided a more accurate D-value evaluation. GFP performed as a suitable fluorescent marker for monitoring disinfection effectiveness.

Non-infectious aortitis: an important cause of severe aortic regurgitation.

From 1995 to 2004, 13 patients with severe aortic regurgitation due to non-infectious aortitis underwent aortic valve surgery at our center. Twenty-eight operations (18 aortic valve replacements and 10 Bentall procedures including 1 aortic root replacement with a homograft) were performed due to a high incidence of prosthetic valve or valved conduit dehiscence (54%). Steroid therapy reduced the incidence of re-operation for anastomotic dehiscence within one year from 90% to 18%. Strategies to prevent dehiscence of the prosthetic aortic valve, which include institution of immunosuppression, replacement of the diseased aorta, and monitoring inflammatory indices, are discussed.

Treatment and outcome of biopsy-proven fulminant myocarditis in adults.

Fulminant myocarditis may be rapidly fatal with severe haemodynamic compromise in previously healthy patients. We reviewed our experience with eight cases of biopsy-proven fulminant myocarditis (seven cases with lymphocytic myocarditis and one with eosinophilic myocarditis). Immunosuppression was given in seven out of eight cases. Mechanical circulatory support was required in 50% of the patients. Time from onset of illness to recovery of ventricular function varied from 12 to 17 days. All except one patient were alive at a mean follow-up of 4.4 years after the acute illness. Patients with acute fulminant myocarditis should be treated aggressively with immunosuppression and, if necessary, mechanical circulatory support during the first 2 to 3 weeks of the illness because of the reversible nature of this illness and good long-term prognosis.

Intrathoracic impedance monitoring in patients with heart failure: correlation with fluid status and feasibility of early warning preceding hospitalization.

BACKGROUND: Patients with heart failure are frequently hospitalized for fluid overload. A reliable method for chronic monitoring of fluid status is therefore desirable. We evaluated an implantable system capable of measuring intrathoracic impedance to identify potential fluid overload before heart failure hospitalization and to determine the correlation between intrathoracic impedance and standard measures of fluid status during hospitalization. METHODS AND RESULTS: Thirty-three patients with NYHA class III and IV heart failure were implanted with a special pacemaker in the left pectoral region and a defibrillation lead in the right ventricle. Intrathoracic impedance was regularly measured and recorded between the lead and the pacemaker case. During hospitalizations, pulmonary capillary wedge pressure and fluid status were monitored. Ten patients were hospitalized for fluid overload 25 times over 20.7+/-8.4 months. Intrathoracic impedance decreased before each admission by an average of 12.3+/-5.3% (P<0.001) over an average of 18.3+/-10.1 days. Impedance reduction began 15.3+/-10.6 days (P<0.001) before the onset of worsening symptoms. There was an inverse correlation between intrathoracic impedance and pulmonary capillary wedge pressure (r=-0.61, P<0.001) and between intrathoracic impedance and net fluid loss (r=-0.70, P<0.001) during hospitalization. Automated detection of impedance decreases was 76.9% sensitive in detecting hospitalization for fluid overload, with 1.5 false-positive (threshold crossing without hospitalization) detections per patient-year of follow-up. CONCLUSIONS: Intrathoracic impedance is inversely correlated with pulmonary capillary wedge pressure and fluid balance and decreased before the onset of patient symptoms and before hospital admission for fluid overload. Regular monitoring of impedance may provide early warning of impending decompensation and diagnostic information for titration of medication.