Novel Pressure-Regulated Deployment Strategy for Improving the Safety and Efficacy of Balloon-Expandable Transcatheter Aortic Valves.

OBJECTIVES: The authors propose a novel pressure-regulated method for balloon-expandable transcatheter heart valve (THV) deployment, aimed at optimizing prosthesis-annulus apposition while preventing significant tissue injury. BACKGROUND: The optimal method for balloon-expandable THV deployment remains debated. Current protocols are volume dependent, relying on under- and overfilling of the deployment apparatus. During deployment, the annular wall tension exerted by the expanding prosthesis is determined by maximal THV diameter and balloon pressure (Laplace's law). METHODS: Three hundred thirty consecutive patients with severe native aortic stenosis who underwent TAVR with SAPIEN 3 THVs were included. One hundred and six patients were considered at high risk for annular rupture. THVs were deployed until reaching a predetermined balloon pressure. Postdilatation was performed to reduce mild or greater angiographic paravalvular regurgitation (PVR). Using a biomechanical model, annular wall stress was estimated for each case and assessed against rates of postdilatation, mild or greater PVR on transthoracic echocardiography, new permanent pacemaker placement or left bundle branch block, and annular rupture. RESULTS: Patients with wall stress >3 MPa had reduced postdilatation rate (P < 0.001) and reduced final PVR (P = 0.014). Annular rupture occurred in 2 of 3 high-risk patients with wall stress >3.5 MPa (3.69 and 3.84 MPa); no rupture occurred in 95 high-risk patients with wall stress ≤3.5 MPa. We defined a single target deployment pressure per THV size to ensure deployment within target wall stress levels of 3 to 3.5 MPa: 6.25 atm for 23-mm THVs, 5.5 atm for 26-mm THVs, and 5 atm for 29-mm THVs. Patients within this target range (n = 136) had a 10.0% postdilatation rate, 12.7% mild PVR, and no moderate to severe PVR. The relationship between balloon filling volume and associated pressure and wall stress was inconsistent. CONCLUSIONS: Pressure-regulated THV deployment is a simple, reproducible, safe, and effective method, regardless of high-risk anatomical complexities.

Intraoperative Retinal Changes May Predict Surgical Outcomes After Epiretinal Membrane Peeling.

Purpose: To investigate whether intraoperative retinal changes during epiretinal membrane (ERM) peeling affect anatomic or functional outcomes after surgery. Methods: We measured retinal thickness using an intraoperative optical coherence tomography (iOCT) device in patients undergoing pars plana vitrectomy with membrane peeling for idiopathic ERM. Changes in intraoperative central macular thickness (iCMT) were compared with postoperative improvements in CMT and best-corrected visual acuity (VA). Results: Twenty-seven eyes from 27 patients (mean age 68 years) underwent iOCT-assisted ERM peeling surgery. Before surgery, mean VA was logMAR 0.50 ± 0.36 (Snellen 20/63), and mean baseline CMT was 489 ± 82 µm. Mean iCMT before peeling was 477 ± 87 µm, which correlated well with preoperative CMT (P < 0.001). Mean change in iCMT was -39.6 ± 37 µm (range -116 to +77 µm). After surgery, VA improved to logMAR 0.40 ± 0.38 (Snellen 20/50) at month 1 and logMAR 0.27 ± 0.23 (Snellen 20/37) at month 3, whereas CMT decreased to 397 ± 44 µm and 396 ± 51 µm at months 1 and 3. Eyes that underwent greater amount of iCMT change (absolute value of iCMT change) were associated with greater CMT reduction at month 1 (P < 0.001) and month 3 (P = 0.010), whereas those with greater intraoperative thinning (actual iCMT change) showed a trend toward better VA outcomes at months 1 (P = 0.054) and 3 (P = 0.036). Conclusions: Intraoperative changes in retinal thickness may predict anatomic and visual outcomes after idiopathic ERM peeling surgery. Translational Relevance: Our study suggests that intraoperative retinal tissue response to ERM peeling surgery measured by iOCT may be a prognostic indicator for restoration of retinal architecture and for visual acuity outcomes.

Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol.

INTRODUCTION: Older patients undergoing cardiac surgery carry the highest risk for developing major postoperative neurocognitive disorder (postoperative NCD or P-NCD) with up to 25% incidence 3 months after surgery. P-NCD is associated with significant morbidity, mortality, loss of independence, premature retirement and increased healthcare costs. This multicentre randomised trial is investigating the efficacy of postoperative dexmedetomidine sedation in reducing the incidence of major P-NCD after cardiac surgery compared with standard protocols. CODEX will be the largest interventional trial with major P-NCD as the primary outcome. METHODS AND ANALYSIS: CODEX is recruiting patients ≥60 years old, undergoing elective cardiac surgery and without pre-existing major cognitive dysfunction or dementia. Eligible participants are randomised to receive postoperative dexmedetomidine or standard institutional sedation protocols in the intensive care unit. Baseline preoperative cognitive function is assessed with the computer-based Cogstate Brief Battery. The primary outcome, major P-NCD, 3 months after surgery is defined as a decrease in cognitive function ≥1.96 SD below age-matched, non-operative controls. Secondary outcomes include delirium, major P-NCD at 6/12 months, depressive symptoms, mild P-NCD and quality of surgical recovery at 3/6/12 months. The specific diagnostic criteria used in this protocol are consistent with the recommendations for clinical assessment and management of NCD from the Nomenclature Consensus Working Group on perioperative cognitive changes. Intention-to-treat analysis will compare major P-NCD at 3 months between study groups. ETHICS AND DISSEMINATION: CODEX was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB) (Project ID 1743). This will be the first multicentre, randomised controlled trial to assess the efficacy of a pharmacological intervention to reduce the incidence of major P-NCD after cardiac surgery in patients ≥60 years old. Dissemination of the study results will include briefings of key findings and interpretation, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04289142.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

A pilot study comparing parent and adolescent online health information seeking behaviours in elective pediatric surgical situations.

PURPOSE: Little is known of how children seek health information. This study evaluates online health information (OHI) seeking behaviours in adolescents undergoing major elective surgical procedures and compares responses within parent-child dyads. METHODS: With institutional approval, we prospectively surveyed parents of children admitted to our institution for major elective operations between November 2017 and November 2018, using convenience sampling. Patients aged 12 years and above were also invited. Each respondent completed an anonymized modification of a previously published survey on Internet usage. Chi squared tests were used for categorical data, with significance at P value < 0.05. RESULTS: Ninety-one parents and 19 patients (median age 15 years, range 12-18) responded, with 13 parent-child pairs. Daily Internet access was reported by 84 (93%) parents and 18 (95%) children, but OHI was sought in 77% of parents and 74% of children. Six (32%) children could not name their admitting condition, compared to 10 (11%) parents. Nine (50%) children consulted family and friends for information compared to 27 (30%) parents. Parents were more likely to access hospital websites (n = 15, 44%) compared to no children (p = 0.01), while most children (n = 7, 70%) accessed non-health websites (e.g. Wikipedia). In the 13 parent-child pairs, only one parent accurately assessed what their child understood of their condition. Most patients (63.6%) did not understand the aspects of their condition that their parents deemed important. CONCLUSIONS: This study highlights the differences in parental and child behaviours. Children are equally important to include when counselling. Surgeons can guide both parties to reliable Internet sources for health information.

An unusual case of stent thrombosis: a case report.

BACKGROUND: Stent thrombosis is a serious and potentially life-threatening complication of percutaneous coronary intervention. It often presents dramatically, typically resulting in ST-elevation myocardial infarction which is associated with a high mortality rate. Premature discontinuation of antiplatelet therapy in the initial 30 days after stenting is arguably the most important predictor of stent thrombosis. In some cases, discontinuation of therapy is unintentional, such as in patients with short-bowel length or malabsorption syndromes. CASE SUMMARY: A 70-year-old man presented to our hospital with stent thrombosis due to non-absorption of antiplatelet agents, 3 days after an elective percutaneous intervention to the right coronary artery. The patient, who had had a laparoscopic high anterior resection due to previous colorectal cancer, had noticed tablets passing whole into his colostomy bag. Repeat balloon angioplasty and stenting were performed and the patient received further antiplatelet therapy in a crushed form. DISCUSSION: Drug absorption in the gastrointestinal tract is altered when a significant length of the gut has been resected. Reduced intestinal luminal transit time and insufficient contact time with intestinal mucosa leads to reduced bioavailability of drugs and increased risk of stent thrombosis. The aetiology of stent thrombosis can be investigated with intravascular imaging techniques and platelet function testing. Management includes using different drug formulations and doses and monitoring the outcomes of therapy. In some cases, it may also be appropriate to involve a gastroenterology team, preferably in the multidisciplinary environment of an intestinal rehabilitation centre.

Physician engagement: the Vancouver Medical Staff Association engagement charter.

Engagement of physicians with their healthcare community or institution should be a central issue in healthcare because it can be translated into improved patient care, enhanced well-being for physicians as well as safer, more effective and less costly healthcare. To accomplish the mission/goal of meaningful physician engagement, we set about to establish a 'charter' for physician engagement. We defined our concept of meaningful physician engagement and customised the engagement spectrum construct for physician relationship with their healthcare community or institution. While recognising the importance of physician leaders within the hierarchical system for efficacy of organisational management, relying only on physicians in formal executive positions is insufficient for developing physician engagement. There is a need for widespread physician engagement across the organisation. The objective is both an improvement in patient care and in physician well-being.

Gastrointestinal disease burden and mortality: A public hospital-based study from 2005 to 2014.

BACKGROUND AND AIM: Gastrointestinal (GI) diseases account for substantial morbidity, mortality, and health care utilization. This public hospital-based study assessed the incidence and time trend of hospitalization and mortality of major GI diseases over one decade. METHODS: We conducted an observational study using population-wide database managed by the Hong Kong Hospital Authority with a principal diagnosis of GI diseases defined by International Classification of Disease, 9th Revision, Clinical Modification coding. We measured age-standardized incidence of hospitalization, emergency admissions, multiple admissions, and in-hospital mortality from 2005 to 2014 using Poisson regression. RESULTS: The annual incidence of hospitalization for GI diseases increased from 4713 to 5241 per 100 000 discharges (incidence rate ratio [IRR] = 1.004; 95% confidence interval [CI]: 1.003-1.005). GI infections and cancers showed the highest rates of hospitalization in 2014. Hospitalization for GI cancers (IRR = 1.014; 95% CI: 1.013-1.016) and non-infectious enterocolitis (IRR = 1.058; 95% CI: 1.055-1.061) increased, whereas peptic ulcer disease has decreased. Hospitalization for Crohn's disease showed the most significant rise (126%). Annual incidence of hospitalization for Clostridium difficile infections increased by fivefold (IRR = 1.221; 95% CI: 1.178-1.266), while a 66% reduction was observed for peptic ulcer bleeding (IRR = 0.894; 95% CI: 0.889-0.899). GI cancers had the highest in-hospital mortality rate in 2014, especially colorectal cancer and gastric cancer. CONCLUSIONS: This study showed an increased hospitalization burden of GI cancers and Crohn's disease, and a reduction in overall mortality for GI diseases. These data provide insight into epidemiological changes of GI diseases in the 21st century and implications for hospital burden and need of resource re-allocation.

Macular Fluid Reduces Reproducibility of Choroidal Thickness Measurements on Enhanced Depth Optical Coherence Tomography.

PURPOSE: To determine if different types of retinal fluid in the central macula affect the reproducibility of choroidal thickness (CT) measurements on enhanced depth imaging optical coherence tomography (EDI-OCT). DESIGN: Retrospective reliability analysis. METHODS: EDI-OCT images were obtained and the choroidal-scleral junction was analyzed through semiautomated segmentation. CT was measured at the fovea and averaged across the central 3-mm horizontal segment. Demographic data, central macular thickness, and type of fluid present were recorded. Intragrader and intergrader repeatability were assessed using the intraclass correlation coefficient (ICC) and coefficient of repeatability (CR). RESULTS: Of 124 eyes analyzed, 60 (48.4%) had diabetic macular edema, 32 (25.8%) had neovascular age-related macular degeneration, and 32 (25.8%) had other causes of fluid. Intergrader ICC (CR) was 0.95 (74.1 µm) and 0.96 (63.9 µm) for subfoveal and average CT, respectively. CR was similar across various causes of retinal fluid, but was worst for subretinal fluid compared to intraretinal or sub-retinal pigment epithelial fluid. CR also worsened with increasing choroidal thickness, but was not affected by retinal thickness. Intragrader repeatability was generally greater than intergrader values, and followed the same trend. CONCLUSIONS: The presence of macular fluid reduces CT measurement reproducibility, particularly in eyes with subretinal fluid and greater choroidal thickness. A difference of 74.1 µm in subfoveal CT or 63.9 µm in average CT may be necessary to detect true clinical change in eyes with macular fluid.

Interventions for idiopathic steroid-resistant nephrotic syndrome in children.

BACKGROUND: The majority of children who present with their first episode of nephrotic syndrome achieve remission with corticosteroid therapy. Children who fail to respond may be treated with immunosuppressive agents including calcineurin inhibitors (cyclosporin or tacrolimus) and with non-immunosuppressive agents such as angiotensin-converting enzyme inhibitors (ACEi). Optimal combinations of these agents with the least toxicity remain to be determined. This is an update of a review first published in 2004 and updated in 2006 and 2010. OBJECTIVES: To evaluate the benefits and harms of different interventions used in children with idiopathic nephrotic syndrome, who do not achieve remission following four weeks or more of daily corticosteroid therapy. SEARCH METHODS: We searched Cochrane Kidney and Transplant's Specialised Register (up to 2 March 2016) through contact with the Information Specialist using search terms relevant to this review. SELECTION CRITERIA: RCTs and quasi-RCTs were included if they compared different immunosuppressive agents or non-immunosuppressive agents with placebo, prednisone or other agent given orally or parenterally in children aged three months to 18 years with SRNS. DATA COLLECTION AND ANALYSIS: Two authors independently searched the literature, determined study eligibility, assessed risk of bias and extracted data. For dichotomous outcomes, results were expressed as risk ratios (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Nineteen RCTs (820 children enrolled; 773 evaluated) were included. Most studies were small. Eleven studies were at low risk of bias for allocation concealment and only four studies were at low risk of performance bias. Fifteen, eight and 10 studies were at low risk of detection bias, attrition bias and reporting bias respectively. Cyclosporin when compared with placebo or no treatment significantly increased the number of children who achieved complete remission. However this was based on only eight children who achieved remission with cyclosporin compared with no children who achieved remission with placebo/no treatment in three small studies (49 children: RR 7.66, 95% CI 1.06 to 55.34). Calcineurin inhibitors significantly increased the number with complete or partial remission compared with IV cyclophosphamide (2 studies, 156 children: RR 1.98, 95% CI 1.25 to 3.13; I2 = 20%). There was no significant differences in the number who achieved complete remission between tacrolimus versus cyclosporin (1 study, 41 children: RR 0.86, 95% CI 0.44 to 1.66), cyclosporin versus mycophenolate mofetil plus dexamethasone (1 study, 138 children: RR 2.14, 95% CI 0.87 to 5.24), oral cyclophosphamide with prednisone versus prednisone alone (2 studies, 91 children: RR 1.06, 95% CI 0.61 to 1.87), IV versus oral cyclophosphamide (1 study, 11 children: RR 3.13, 95% CI 0.81 to 12.06), IV cyclophosphamide versus oral cyclophosphamide plus IV dexamethasone (1 study, 49 children: RR 1.13, 95% CI 0.65 to 1.96), and azathioprine with prednisone versus prednisone alone (1 study, 31 children: RR 0.94, 95% CI 0.15 to 5.84). One study found no significant differences between three agents (cyclophosphamide, mycophenolate mofetil, leflunomide) used in combination with tacrolimus and prednisone. One study found no significant difference in the percentage reduction in proteinuria (31 children: -12; 95% CI -73 to 110) between rituximab with cyclosporin/prednisolone and cyclosporin/prednisolone alone. Two studies reported ACEi significantly reduced proteinuria. AUTHORS' CONCLUSIONS: To date RCTs have demonstrated that calcineurin inhibitors increase the likelihood of complete or partial remission compared with placebo/no treatment or cyclophosphamide. For other regimens assessed, it remains uncertain whether the interventions alter outcomes because the certainty of the evidence is low. Further adequately powered, well designed RCTs are needed to evaluate other regimens for children with idiopathic SRNS. Since SRNS represents a spectrum of diseases, future studies should enrol children from better defined groups of patients with SRNS.

Venous thromboembolism in medical patients during hospitalisation and 3†months after hospitalisation: a prospective observational study.

OBJECTIVES: This study was conducted to assess the incidence and risk factors for venous thromboembolism (VTE) in a cohort of medical patients both during the period of hospitalisation and following discharge. DESIGN: This was a prospective observational study to document the risk profile and incidence of VTE posthospitalisation among all medical patients admitted to our institution during the trial period. SETTINGS: Primary healthcare. Single tertiary referral centre, Tasmania, Australia. PARTICIPANTS: A total of 986 patients admitted to the medical ward between January 2012 and September 2012 were included in the study with male to female ratio of 497:489. The mean age of patients was 68 years (range 17-112, SD 16). RESULTS: Overall, 54/986 patients (5.5%) had a VTE during the study period. Of these, 40/54 (74.1%) occurred during hospitalisation and 14/54 (25.9%) occurred following discharge. VTE risk factors revealed in multivariate analysis to be associated with a previous diagnosis of VTE (p<0.001, OR=6.63, 95% CI 3.3 to 13.36), the occurrence of surgery within the past 30 days (p<0.001, OR=2.52, 95% CI 1.33 to 4.79) and an admission diagnosis of pulmonary disease (p<0.01, OR 3.61, 95% CI 1.49 to 8.76). Mobility within 24 hours of admission was not associated with an increased risk. There was risk of VTE when the length of stay prolonged (p=0.046, OR=1.01, 95% CI 1.00 to 1.03), however it was not sustained with multivariate modelling. VTE-specific prophylaxis was used in 53% of the studied patients. Anticoagulation including antiplatelet agents were administered in 63% of patients who developed VTE. CONCLUSIONS: This prospective observational study found that 5.5% of the studied patients developed VTE. Among those, 25.9% (14/54) of patients had a detected VTE posthospitalisation with this risk being increased if there was a history of VTE, recent surgery and pulmonary conditions. Thromboprophylaxis may be worth considering in these cohorts. Further study to confirm these findings are warranted. TRIAL REGISTRATION NUMBER: ACTRN12611001255976.

Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

BACKGROUND: The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. METHODS: Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. RESULTS: Compared with controls, patients had significantly lower LV global 3D strain (P < 0.001), twist (P = 0.01), torsion (P = 0.04), and ejection fraction (P < 0.001) and greater SDI (P < 0.001). The GPI was lower in patients than controls (P < 0.001). T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001) and GPI (r = 0.63, P = 0.001), and negatively with SDI (r = -0.44, P = 0.03). The AUCs of GPI, global 3D strain, ejection fraction, torsion, and 1/SDI were 0.94, 0.90, 0.87, 0.82, and 0.70, respectively. The GPI cutoff of 2.7°/cm had a sensitivity of 94.9% and a specificity of 88.9% of differentiating patients with from those without myocardial iron overload. CONCLUSIONS: The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia.

Is cardiac magnetic resonance imaging as accurate as echocardiography in the assessment of aortic valve stenosis?

A best evidence topic was written according to a structured protocol. The question addressed was: is cardiac magnetic resonance (CMR) imaging as accurate as echocardiography in the assessment of aortic valve stenosis? Altogether 239 papers were found using the reported search. Only 12 demonstrated the best evidence to answer the clinical question. Nine of these 12 papers found CMR to correlate well with transthoracic echocardiography (TTE) or transoesophageal echocardiography (TOE) in the evaluation of aortic valve stenosis. When aortic valve areas were measured with cardiac tomography (CT) or cardiac catheterization (CC), four papers found CMR to be more accurate than TTE. Eight of 12 papers found CMR to have excellent reliability and reproducibility, as demonstrated by the low inter- and intraobserver variability. Four papers did not estimate intra- or interobserver variability. One paper noted a sensitivity and specificity of 96 and 100%, respectively, when using CMR to detect severe aortic stenosis (AS) that had been diagnosed during CC. A second paper noted a lower sensitivity and specificity of 78 and 89%, respectively, but this was still better than the sensitivities and specificities found when using TOE or TTE to detect severe AS, as noted on CC. We conclude that current evidence finds echocardiography and CMR to be equally reliable in assessing aortic stenosis. CMR has better inter- and intraobserver reliability and demonstrates an advantage over echocardiography in the detection of severe AS with greater specificity and sensitivity. The final choice, however, is as likely to be influenced by the availability of magnetic resonance imaging and expertise in interpreting the results as by accuracy and reliability.

Pulmonary valve replacement and quality-of-life assessment.

BACKGROUND: Chronic pulmonary regurgitation is common after repair of tetralogy of Fallot. Despite the deleterious effects of chronic pulmonary regurgitation on right ventricular function, many patients with repaired tetralogy of Fallot remain asymptomatic. Health is defined not only by the absence of disease but also by physical, mental, and social wellbeing. We sought to examine the impact of pulmonary valve replacement on quality of life in asymptomatic patients with repaired tetralogy of Fallot and chronic pulmonary regurgitation. METHODS: From January 2009 to December 2012, 25 (18 male) asymptomatic patients (mean age 23.4 ± 7.4 years) who underwent pulmonary valve replacement for significant pulmonary regurgitation were recruited. Cardiac magnetic resonance was performed pre- and postoperatively. Quality of life was assessed using the Chinese version of the SF-36v2 evaluation tool. Demographics, clinical data, magnetic resonance findings, and quality-of-life scores were collected and calculated for comparison. RESULTS: After surgery, the indexed right ventricular end-diastolic volume (193 ± 47.3 vs. 105.6 ± 29.6 mL m(-2), p < 0.001) and indexed right ventricular end-systolic volume (108.5 ± 32.9 vs. 61.1 ± 23 mL m(-2), p < 0.001) decreased significantly. The response rates for pre- and postoperative quality-of-life assessments were 100%. Patients demonstrated improvements in all 8 domains of the SF-36v2 assessment. The physical (46.5 ± 6.6 vs. 49.9 ± 6.4, p = 0.012) and mental (43.7 ± 7.8 vs. 51.9 ± 7.6, p < 0.001) component summary scores increased after surgery. CONCLUSION: Pulmonary valve replacement can improve the quality of life in patients with chronic asymptomatic pulmonary regurgitation.

Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 µU/mL in patient serum samples.

Right Atrial Mechanics Long-Term after Biventricular Repair of Pulmonary Atresia or Stenosis with Intact Ventricular Septum.

BACKGROUND: This study tested the hypothesis that right atrial (RA) mechanics are altered in patients after repair of pulmonary atresia with intact ventricular septum (PAIVS) and pulmonary stenosis (PS) and to explore their relationships with right ventricular (RV) diastolic function and P-wave indices. METHODS: Thirty-six adult patients, 16 with PAIVS and 20 with PS patients, and 20 age-matched healthy subjects were studied. Right atrial mechanics were assessed using speckle tracking echocardiography (STE) with quantification of positive, negative, and total strain, and strain rates at ventricular systole (aSRs ), early diastole (aSRed ), and atrial contraction (aSRac ). Right ventricular diastolic function was assessed by Doppler interrogation and STE. Maximum P-wave duration and P-wave dispersion were measured. RESULTS: Compared with controls, PAIVS and PS patients had significantly lower RA positive and total strain, aSRs and aSRed (all P < 0.05). Parameters of RV diastolic function including transtricuspid early (E) and late (A) diastolic inflow velocities, E/A ratio, early diastolic tricuspid annular velocity (e), early to late diastolic annular velocity ratio, E/e ratio, and RV early diastolic strain rate were found to correlate significantly with RA positive and total strain and aSRed (all P < 0.05). Maximum P-wave duration and P-wave dispersion increased progressively across control, PS, and PAIVS groups (P for trend <0.001). Both P-wave indices correlated negatively with RA positive strain, total strain, and aSRed (all P < 0.05). CONCLUSION: Impairment of RA mechanics occurs in patients long term after repair of PAIVS and PS and is associated with RV diastolic dysfunction, longer P-wave duration, and greater P-wave dispersion.

Fatal Insulin Overdoses: Case Report and Update on Testing Methodology.

Suicidal insulin overdoses are an under-recognized and uncommon cause of death, often relying on scene and nonspecific autopsy findings. Here, we present a case report of a fatal exogenous insulin overdose in a patient with type 1 diabetes. In our case, there were no contributory autopsy findings; however, serum analog aspart insulin levels were c. 10× the predicted therapeutic upper limit (4000, reference 6.6-55 uU/mL), which correlated with scene findings. This was specifically determined by a newly developed immunocapture liquid chromatography-tandem mass spectrometry assay, able to discriminate between various synthetic insulin analogs. Total insulin levels by immunoassay were highly elevated on the Siemens Advia Centaur, but not the Roche platforms (4741 vs. 5.2 uU/mL, respectively), showing variable sensitivity of detection within the same analog depending on assay. We discuss the prevalence and features to look for at autopsy in these types of cases. Additionally, analytical options for testing insulin levels, including new methodologies, guidance on collection of samples, as well as an outline of available historical reference range data are discussed.