Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: In the ongoing, randomised, double-blind phase 3 TOPAZ-1 study, durvalumab, a PD-L1 inhibitor, plus gemcitabine and cisplatin was associated with significant improvements in overall survival compared with placebo, gemcitabine, and cisplatin in people with advanced biliary tract cancer at the pre-planned intermin analysis. In this paper, we present patient-reported outcomes from TOPAZ-1. METHODS: In TOPAZ-1 (NCT03875235), participants aged 18 years or older with previously untreated, unresectable, locally advanced, or metastatic biliary tract cancer with an Eastern Cooperative Oncology Group performance status of 0 or 1 and one or more measurable lesions per Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1) were randomly assigned (1:1) to the durvalumab group or the placebo group using a computer-generated randomisation scheme. Participants received 1500 mg durvalumab or matched placebo intravenously every 3 weeks (on day 1 of the cycle) for up to eight cycles in combination with 1000 mg/m2 gemcitabine and 25 mg/m2 cisplatin intravenously on days 1 and 8 every 3 weeks for up to eight cycles. Thereafter, participants received either durvalumab (1500 mg) or placebo monotherapy intravenously every 4 weeks until disease progression or other discontinuation criteria were met. Randomisation was stratified by disease status (initially unresectable vs recurrent) and primary tumour location (intrahepatic cholangiocarcinoma vs extrahepatic cholangiocarcinoma vs gallbladder cancer). Patient-reported outcomes were assessed as a secondary outcome in all participants who completed the European Organisation for Research and Treatment of Cancer's 30-item Quality of Life of Cancer Patients questionnaire (QLQ-C30) and the 21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Module (QLQ-BIL21). We calculated time to deterioration-ie, time from randomisation to an absolute decrease of at least 10 points in a patient-reported outcome that was confirmed at a subsequent visit or the date of death (by any cause) in the absence of deterioration-and adjusted mean change from baseline in patient-reported outcomes. FINDINGS: Between April 16, 2019, and Dec 11, 2020, 685 participants were enrolled and randomly assigned, 341 to the durvalumab group and 344 to the placebo group. Overall, 345 (50%) of participants were male and 340 (50%) were female. Data for the QLQ-C30 were available for 318 participants in the durvalumab group and 328 in the placebo group (median follow-up 9·9 months [IQR 6·7 to 14·1]). Data for the QLQ-BIL21 were available for 305 participants in the durvalumab group and 322 in the placebo group (median follow-up 10·2 months [IQR 6·7 to 14·3]). The proportions of participants in both groups who completed questionnaires were high and baseline scores were mostly similar across treatment groups. For global health status or quality of life, functioning, and symptoms, we noted no difference in time to deterioration or adjusted mean changes from baseline were observed between groups. Median time to deterioration of global health status or quality of life was 7·4 months (95% CI 5·6 to 8·9) in the durvalumab group and 6·7 months (5·6 to 7·9) in the placebo group (hazard ratio 0·87 [95% CI 0·69 to 1·12]). The adjusted mean change from baseline was 1·23 (95% CI -0·71 to 3·16) in the durvalumab group and 0·35 (-1·63 to 2·32) in the placebo group. INTERPRETATION: The addition of durvalumab to gemcitabine and cisplatin did not have a detrimental effect on patient-reported outcomes. These results suggest that durvalumab, gemcitabine, and cisplatin is a tolerable treatment regimen in patients with advanced biliary tract cancer. FUNDING: AstraZeneca.

Plain language summary of the TOPAZ-1 study: durvalumab and chemotherapy for advanced biliary tract cancer.

WHAT IS THIS SUMMARY ABOUT?: This is a summary describing the results of a Phase III study called TOPAZ-1. The study looked at treatment with durvalumab (a type of immunotherapy) and chemotherapy to treat participants with advanced biliary tract cancer (BTC). Advanced BTC is usually diagnosed at late stages of disease, when it cannot be cured by surgery. This study included participants with advanced BTC who had not received previous treatment, or had their cancer come back at least 6 months after receiving treatment or surgery that aimed to cure their disease. Participants received treatment with durvalumab and chemotherapy or placebo and chemotherapy. The aim of this study was to find out if treatment with durvalumab and chemotherapy could increase the length of time that participants with advanced BTC lived, compared with placebo and chemotherapy. WHAT WERE THE RESULTS OF THE STUDY?: Participants who took durvalumab and chemotherapy had a 20% lower chance of experiencing death at any point in the study compared with participants who received placebo and chemotherapy. The side effects experienced by participants were similar across treatment groups, and less than 12% of participants in either treatment group had to stop treatment due to treatment-related side effects. WHAT DO THE RESULTS OF THE STUDY MEAN?: Overall, these results support durvalumab and chemotherapy as a new treatment option for people with advanced BTCs. Based on the results of this study, durvalumab is now approved for the treatment of adults with advanced BTCs in combination with chemotherapy by government organizations in Europe, the United States and several other countries.

Understanding the patient experience in hepatocellular carcinoma: a qualitative patient interview study.

PURPOSE: This study aimed to elucidate the patient experience of hepatocellular carcinoma (HCC) to guide patient-centered outcome measurement in drug development. METHODS: Patients with HCC participated in qualitative interviews to elicit disease-related signs/symptoms and impacts, using discussion guides developed from literature searches and discussions with oncologists. Interview participants rated the disturbance of their experiences (0-10 scale). A conceptual model was developed and mapped against patient-reported outcome (PRO) instruments identified from database reviews. RESULTS: Interviews were conducted with 25 individuals with HCC (68% were men; median age: 63 years; 12% Barcelona clinic liver cancer (BCLC) stage A; 32% stage B; and 56% stage C) in the USA. Fifty-one HCC-related concepts were identified from the interviews and were grouped into eight sign/symptom categories (eating behavior/weight changes; extremities [arms, legs]; fatigue and strength; gastrointestinal; pain; sensory; skin; other) and four impact categories (emotional; physical; cognitive function; other) for the conceptual model. The most prevalent and disturbing experiences across the disease stages were fatigue/lack of energy and emotional impacts such as frustration, fear, and depression. Abdominal pain and skin-related issues were particularly common and disturbing in individuals with HCC stage C. The EORTC QLQ-C30 and HCC18 were identified as commonly used PRO instruments in HCC studies and captured the relevant signs/symptoms associated with the patient experience. CONCLUSION: Patients with HCC reported a range of signs/symptoms and impacts that negatively affect daily functioning and quality of life. Including PRO measures in HCC clinical trials can provide meaningful patient perspectives during drug development.

Allopurinol use during pediatric acute lymphoblastic leukemia maintenance therapy safely corrects skewed 6-mercaptopurine metabolism, improving inadequate myelosuppression and reducing gastrointestinal toxicity.

BACKGROUND: Inadequate myelosuppression during maintenance therapy for acute lymphoblastic leukemia (ALL) is associated with an increased risk of relapse. One mechanism is skewed metabolism of 6-mercaptopurine (6MP), a major component of maintenance therapy, which results in preferential formation of the hepatotoxic metabolite (6-methyl mercaptopurine [6MMP]) with low levels of the antileukemic metabolite, 6-thioguanine nucleotides (6TGN). Allopurinol can modify 6MP metabolism to favor 6TGN production and reduce 6MMP. METHODS: Patients in maintenance were considered for allopurinol treatment who had the following features: (a) Grade ≥3 hepatotoxicity; (b) Grade ≥2 nonhepatic gastrointestinal (GI) toxicity; or (c) persistently elevated absolute neutrophil count (ANC) despite >150% protocol dosing of oral chemotherapy. RESULTS: From 2013 to 2017, 13 ALL patients received allopurinol: nine for hepatotoxicity, five for inadequate myelosuppression, and three for nonhepatic GI toxicity (four met multiple criteria). Allopurinol was well tolerated, without significant adverse events. Allopurinol resulted in a significant decrease in the average 6MMP/6TGN ratio (mean reduction 89.1, P = .0001), with a significant increase in 6TGN (mean 550.4, P = .0008) and a significant decrease in 6MMP (mean 13 755, P = .0013). Patients with hepatotoxicity had a significant decrease in transaminase elevation after starting allopurinol (alanine transaminase [ALT] mean decrease 22.1%, P = .02), and all with nonhepatic GI toxicity had improved symptoms. Those with inadequate myelosuppression had a significant increase in the time with ANC in goal (mean increase 26.4%, P = .0004). CONCLUSIONS: Allopurinol during ALL maintenance chemotherapy is a safe, feasible, and effective intervention for those who have altered metabolism of 6MP causing toxicity or inadequate myelosuppression.

International recommendations for electrocardiographic interpretation in athletes.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural, or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly over the last decade; pushed by a growing body of scientific data that both tests proposed criteria sets and establishes new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington, to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.

International criteria for electrocardiographic interpretation in athletes: Consensus statement.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly, advanced by a growing body of scientific data and investigations that both examine proposed criteria sets and establish new evidence to guide refinements. On 26-27 February 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington (USA), to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.

Prospective trial of a pediatric ventricular assist device.

BACKGROUND: Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS: We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS: For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS: Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

Berlin Heart EXCOR pediatric ventricular assist device for bridge to heart transplantation in US children.

BACKGROUND: Recent data suggest that the Berlin Heart EXCOR Pediatric ventricular assist device is superior to extracorporeal membrane oxygenation for bridge to heart transplantation. Published data are limited to 1 in 4 children who received the device as part of the US clinical trial. We analyzed outcomes for all US children who received the EXCOR to characterize device outcomes in an unselected cohort and to identify risk factors for mortality to facilitate patient selection. METHODS AND RESULTS: This multicenter, prospective cohort study involved all children implanted with the Berlin Heart EXCOR Pediatric ventricular assist device at 47 centers from May 2007 through December 2010. Multiphase nonproportional hazards modeling was used to identify risk factors for early (<2 months) and late mortality. Of 204 children supported with the EXCOR, the median duration of support was 40 days (range, 1-435 days). Survival at 12 months was 75%, including 64% who reached transplantation, 6% who recovered, and 5% who were alive on the device. Multivariable analysis identified lower weight, biventricular assist device support, and elevated bilirubin as risk factors for early mortality and bilirubin extremes and renal dysfunction as risk factors for late mortality. Neurological dysfunction occurred in 29% and was the leading cause of death. CONCLUSIONS: Use of the Berlin Heart EXCOR has risen dramatically over the past decade. The EXCOR has emerged as a new treatment standard in the United States for pediatric bridge to transplantation. Three-quarters of children survived to transplantation or recovery; an important fraction experienced neurological dysfunction. Smaller patient size, renal dysfunction, hepatic dysfunction, and biventricular assist device use were associated with mortality, whereas extracorporeal membrane oxygenation before implantation and congenital heart disease were not.

Acute-onset choreiform movements in a previously healthy 4-year-old patient.

We report the case of 4-year-old male with sinus venous thrombosis leading to bilateral thalamic and basal ganglia strokes presenting as generalized choreiform movements. Acute-onset chorea in the pediatric population is most commonly associated with Sydenham chorea, which is a manifestation of acute rheumatic fever. Chorea is a much less commonly noted sign of stroke, and when it occurs, it typically presents as hemichorea. Given the unlikely presentation, rapid and appropriate imaging was the key to diagnosis.

Durvalumab plus Gemcitabine and Cisplatin in Advanced Biliary Tract Cancer.

BACKGROUND: Patients with advanced biliary tract cancer have a poor prognosis, and first-line standard of care (gemcitabine plus cisplatin) has remained unchanged for more than 10 years. The TOPAZ-1 trial evaluated durvalumab plus chemotherapy for patients with advanced biliary tract cancer. METHODS: In this double-blind, placebo-controlled, phase 3 study, we randomly assigned patients with previously untreated unresectable or metastatic biliary tract cancer or with recurrent disease 1:1 to receive durvalumab or placebo in combination with gemcitabine plus cisplatin for up to eight cycles, followed by durvalumab or placebo monotherapy until disease progression or unacceptable toxicity. The primary objective was to assess overall survival. Secondary end points included progression-free survival, objective response rate, and safety. RESULTS: Overall, 685 patients were randomly assigned to durvalumab (n=341) or placebo (n=344) with chemotherapy. As of data cutoff, 198 patients (58.1%) in the durvalumab group and 226 patients (65.7%) in the placebo group had died. The hazard ratio for overall survival was 0.80 (95% confidence interval [CI], 0.66 to 0.97; P=0.021). The estimated 24-month overall survival rate was 24.9% (95% CI, 17.9 to 32.5) for durvalumab and 10.4% (95% CI, 4.7 to 18.8) for placebo. The hazard ratio for progression-free survival was 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates were 26.7% with durvalumab and 18.7% with placebo. The incidences of grade 3 or 4 adverse events were 75.7% and 77.8% with durvalumab and placebo, respectively. CONCLUSIONS: Durvalumab plus chemotherapy significantly improved overall survival versus placebo plus chemotherapy and showed improvements versus placebo plus chemotherapy in prespecified secondary end points including progression-free survival and objective response rate. The safety profiles of the two treatment groups were similar. (Funded by AstraZeneca; ClinicalTrials.gov number, NCT03875235.)

Triiodothyronine Supplementation in Infants and Children Undergoing Cardiopulmonary Bypass (TRICC): a multicenter placebo-controlled randomized trial: age analysis.

BACKGROUND: Triiodothyronine levels decrease in infants and children after cardiopulmonary bypass. We tested the primary hypothesis that triiodothyronine (T3) repletion is safe in this population and produces improvements in postoperative clinical outcome. METHODS AND RESULTS: The TRICC study was a prospective, multicenter, double-blind, randomized, placebo-controlled trial in children younger than 2 years old undergoing heart surgery with cardiopulmonary bypass. Enrollment was stratified by surgical diagnosis. Time to extubation (TTE) was the primary outcome. Patients received intravenous T3 as Triostat (n=98) or placebo (n=95), and data were analyzed using Cox proportional hazards. Overall, TTE was similar between groups. There were no differences in adverse event rates, including arrhythmia. Prespecified analyses showed a significant interaction between age and treatment (P=0.0012). For patients younger than 5 months, the hazard ratio (chance of extubation) for Triostat was 1.72. (P=0.0216). Placebo median TTE was 98 hours with 95% confidence interval (CI) of 71 to 142 compared to Triostat TTE at 55 hours with CI of 44 to 92. TTE shortening corresponded to a reduction in inotropic agent use and improvement in cardiac function. For children 5 months of age, or older, Triostat produced a significant delay in median TTE: 16 hours (CI, 7-22) for placebo and 20 hours (CI, 16-45) for Triostat and (hazard ratio, 0.60; P=0.0220). CONCLUSIONS: T3 supplementation is safe. Analyses using age stratification indicate that T3 supplementation provides clinical advantages in patients younger than 5 months and no benefit for those older than 5 months. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00027417.

Predictors of ECMO support in infants with tachycardia-induced cardiomyopathy.

The development of tachycardia-induced cardiomyopathy (TIC) is related to the rate and duration of supraventricular tachycardia (SVT). Infants may be more susceptible to TIC because early symptoms might be unrecognized. Extracorporeal membrane oxygenation (ECMO) may improve outcome in patients with SVT and TIC; however, clinical predictors of infants who require ECMO support have not been determined. The purpose of this study was to identify predictors of the need for ECMO in infants with SVT and TIC. Sixteen infants <6 months of age who experienced resolution of TIC following control of arrhythmia were identified. Three patients (19%) required ECMO support. Comparisons were made between patients who required ECMO and those who did not. The groups were similar with respect to age at presentation, type of SVT, rate of SVT, and degree of ventricular dysfunction. However, patients requiring ECMO had increased median M-mode-derived left ventricular end diastolic dimension (LVED) z-score when compared to the medically managed patents (+2.8 vs. 0.0, P = 0.009). No patient in the medically managed group had an LVED z-score >2.3. Infants presenting with SVT and TIC with LVED z-score >2 are at increased risk for requiring ECMO support and early use of ECMO should be considered.

Understanding Patient Experience in Biliary Tract Cancer: A Qualitative Patient Interview Study.

INTRODUCTION: Patients living with biliary tract cancer (BTC) experience a decline in health-related quality of life (HRQoL). This study aimed to obtain a comprehensive understanding of the patient experience of BTC-related signs/symptoms and the impacts of these on daily functioning and HRQoL. METHODS: Patients with BTC participated in qualitative semi-structured concept elicitation interviews. Signs/symptoms and impacts of BTC were initially explored by targeted literature searches and interviews with five clinicians. Patient interviews were transcribed and coded using qualitative research software. Concept saturation was assessed over five interview waves. A sign/symptom or impact was defined as "salient" if mentioned by ≥ 50% of patients, with a mean disturbance rating of ≥ 5 (0-10 scale). A conceptual model of the patient experience of BTC-related signs/symptoms and impacts was produced. RESULTS: Twenty-three patients from the USA (78% women; median age: 54 years), diagnosed as having early (n = 3), locally advanced (n = 11) or metastatic (n = 9) disease, were interviewed. Sixty-six signs/symptoms and 12 impacts were identified. Of these, 46 signs/symptoms and 8 impacts were not identified from the targeted literature or clinician interviews. Concept saturation was reached by the fourth of five interview waves. Fourteen disease-related signs/symptoms (including fatigue/lack of energy, abdominal pain, lack of appetite, insomnia and diarrhoea) and three impacts (physical, emotional and cognitive impacts) were deemed "salient". The conceptual model included 50 signs/symptoms and 12 impacts. CONCLUSION: Patients with BTC reported a range of signs/symptoms and impacts that negatively affect daily functioning and HRQoL.

Congenital cardiac surgical complications of the integument, vascular system, vascular-line(s), and wounds: consensus definitions from the Multi-Societal Database Committee for Pediatric and Congenital Heart Disease.

A complication is an event or occurrence that is associated with a disease or a healthcare intervention, is a departure from the desired course of events, and may cause, or be associated with, suboptimal outcome. A complication does not necessarily represent a breech in the standard of care that constitutes medical negligence or medical malpractice. An operative or procedural complication is any complication, regardless of cause, occurring (1) within 30 days after surgery or intervention in or out of the hospital, or (2) after 30 days during the same hospitalization subsequent to the operation or intervention. Operative and procedural complications include both intraoperative/intraprocedural complications and postoperative/postprocedural complications in this time interval. The MultiSocietal Database Committee for Pediatric and Congenital Heart Disease has set forth a comprehensive list of complications associated with the treatment of patients with congenital cardiac disease, related to cardiac, pulmonary, renal, haematological, infectious, neurological, gastrointestinal, and endocrinal systems, as well as those related to the management of anaesthesia and perfusion, and the transplantation of thoracic organs. The objective of this manuscript is to examine the definitions of operative morbidity as they relate specifically to a collection of loosely related topics that include the following groups of complications: 1) Complications of the Integument, 2) Complications of the Vascular System, 3) Complications of the Vascular-Line(s), 4) Complications of Wounds. These specific definitions and terms will be used to track morbidity associated with surgical and transcatheter interventions and other forms of therapy in a common language across many separate databases. As surgical survival in children with congenital cardiac disease has improved in recent years, focus has necessarily shifted to reducing the morbidity of congenital cardiac malformations and their treatment. A comprehensive list of complications is presented. This list is a component of a systems-based compendium of complications that will standardize terminology and thereby allow the study and quantification of morbidity in patients with congenital cardiac malformations. Clinicians caring for patients with congenital cardiac disease will be able to use this list for databases, initiatives to improve quality, reporting of complications, and comparing strategies of treatment.

An investigation of Aspergillus cardiac surgical site infections in 3 pediatric patients.

BACKGROUND: Within a 3-month period, 3 pediatric patients at our hospital developed Aspergillus surgical site infections after undergoing cardiac surgery. METHODS: A multidisciplinary team conducted an epidemiologic review of the 3 patients and their infections, operative and postoperative patient care delivery, and routine maintenance of hospital equipment and air-filtration systems and investigated potential environmental exposures within the hospital that may have contributed to the development of these infections. RESULTS: Review of the patients and their infections, operative and postoperative patient care delivery, and routine maintenance did not reveal a source for infection. Inspection of operating room (OR) facilities identified several areas in need of repair. Of the 58 samples of air and equipment exhaust in the ORs and patient care areas, 11 revealed 2 to 4 colony-forming units of various Aspergillus species per cubic meter of air, and the remaining 47 samples were negative for Aspergillus. Eighty-three samples of surfaces and equipment water reservoirs were obtained from the OR and patient care areas. One culture of a soiled liquid nitrogen tank housed between the 2 cardiac ORs revealed 13 colony-forming units of Aspergillus. CONCLUSION: No definitive source was identified, although a soiled liquid nitrogen tank contaminated with Aspergillus and kept near the OR was found and could have been a possible source.

Intraoperative echocardiography for atrioventricular canal: decision-making for surgeons.

Intraoperative echocardiography has become a standard patient management tool in the assessment of the patient undergoing surgical repair of a congenital cardiac defect. Over the past 15 years transesophageal echocardiography has emerged as an integral part of the intraoperative assessment of the congenital cardiac surgery patient. The important role of intraoperative echocardiography is largely because of its ability to define complex anatomy, identify functional abnormalities, and recognize flow disturbances at the time of surgical repair. Intracardiac defects are particularly suited to the strengths of intraoperative transesophageal echocardiography because of the unobstructed windows that can be obtained. This article focuses on how intraoperative echocardiography can guide surgical decision-making in the patient undergoing repair of an atrioventricular canal defect.

International Recommendations for Electrocardiographic Interpretation in Athletes.

Sudden cardiac death (SCD) is the leading cause of mortality in athletes during sport. A variety of mostly hereditary, structural, or electrical cardiac disorders are associated with SCD in young athletes, the majority of which can be identified or suggested by abnormalities on a resting 12-lead electrocardiogram (ECG). Whether used for diagnostic or screening purposes, physicians responsible for the cardiovascular care of athletes should be knowledgeable and competent in ECG interpretation in athletes. However, in most countries a shortage of physician expertise limits wider application of the ECG in the care of the athlete. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from distinctly abnormal findings suggestive of underlying pathology. Since the original 2010 European Society of Cardiology recommendations for ECG interpretation in athletes, ECG standards have evolved quickly over the last decade; pushed by a growing body of scientific data that both tests proposed criteria sets and establishes new evidence to guide refinements. On February 26-27, 2015, an international group of experts in sports cardiology, inherited cardiac disease, and sports medicine convened in Seattle, Washington, to update contemporary standards for ECG interpretation in athletes. The objective of the meeting was to define and revise ECG interpretation standards based on new and emerging research and to develop a clear guide to the proper evaluation of ECG abnormalities in athletes. This statement represents an international consensus for ECG interpretation in athletes and provides expert opinion-based recommendations linking specific ECG abnormalities and the secondary evaluation for conditions associated with SCD.

The waiting game: bridging to paediatric heart transplantation.

BACKGROUND: Although mechanical circulatory support might not increase the number of adults surviving to transplantation, because of the shortage of donor organs, the situation might be different for children. Our aim was to assess the effect of mechanical assist devices to bridge children with end-stage cardiomyopathy to heart transplantation. METHODS: A 5-year retrospective review was undertaken with data from the UK paediatric transplant programme and from bridging to transplant done at two paediatric transplant centres in the UK. FINDINGS: Between Jan 1, 1998 and Dec 31, 2002, 22 children with end-stage cardiomyopathy, median age 5.7 years (range 1.2-17), were supported by a mechanical assist device as a bridge to first heart transplantation, with a 77% survival rate to hospital discharge. Nine were supported by a paracorporeal ventricular assist device, six received transplantation, five survived to discharge (55%), with one late death. 13 were supported by extra-corporeal membrane oxygenation, and 12 were transplanted and survived to discharge (92%) with one late death. With urgent listing, the median waiting time for a heart was 7.5 days (range 1.5-22 days). The correlation between the proportion of patients bridged to transplantation and the proportion of patients dying while on the transplant waiting list was r=-0.93, p=0.02. INTERPRETATION: Our findings lend support to the hypothesis that a national mechanical assist programme to bridge children to transplantation can minimise the number dying while on the heart transplant waiting list. In the context of urgent listing and a short waiting time, extra-corporeal membrane oxygenation seems to provide the safest form of support.

Pulmonary arteriovenous shunting in the normal fetal lung.

OBJECTIVES: We hypothesized that pulmonary arteriovenous shunting (PAVS) is normally present in fetal lungs and that cavopulmonary anastomosis-induced PAVS may represent a return to an earlier morphologic stage of development. BACKGROUND: The surgical superior cavopulmonary anastomosis is performed as part of the staged Fontan pathway to treat univentricular forms of congenital heart disease; PAVS is a known sequela after superior cavopulmonary anastomosis and may have important clinical consequences. Although the etiology and true morphology of the structures responsible for PAVS are unknown, a leading theory is that PAVS is caused by absence of normal hepatic venous drainage to the pulmonary circulation. METHODS: To determine whether normal fetal lungs demonstrate PAVS, we performed contrast echocardiograms on 13 fetal lambs, 8 neonatal lambs, 4 juvenile lambs, and 4 adult sheep using a blended mixture of saline and blood injected directly into the proximal pulmonary artery. RESULTS: Pulmonary arteriovenous shunting was detected by direct epicardial echocardiography in all fetal lambs (n = 13) and neonatal animals studied at one and three days of life (n = 4) and in two of four animals studied at six to nine days of life. Pulmonary arteriovenous shunting was not present in animals studied at four weeks of life (n = 2) and in adult sheep (n = 5). CONCLUSIONS: These studies demonstrate that PAVS is normally present in late gestation fetal and early neonatal lambs but then disappears during the later neonatal period. Furthermore, these findings suggest that PAVS associated with cavopulmonary anastomosis or other processes affecting the developing pulmonary circulation may represent a return to an earlier morphologic stage of development.

Decision making for mechanical cardiac assist in pediatric cardiac surgery.

The practice of pediatric cardiac surgery has evolved to the point where the majority of patients operated on represent the most complex end of the spectrum of congenital heart disease. Given this, the potential role for mechanical cardiac assist will continue to expand. Although extracorporeal membrane oxygenation remains the mainstay of mechanical circulatory assist, the increased use of centrifugal ventricular assist devices is changing the approach to the treatment of acute cardiac failure. A range of newly developed implantable and paracorporeal devices is beginning to make its way into the clinical practice of pediatric cardiac surgery. This article addresses the different types of support available for mechanical cardiac assist and the clinical considerations in selecting the appropriate device.