Ventricular bigeminy associated with myocardial ischemia in a dog with a colonic torsion: a case report.

BACKGROUND: Ventricular bigeminy due to myocardial ischemia has been reported in humans as well as in canine patients with obstructive gastrointestinal diseases. This is the first case report of ventricular bigeminy in a dog with a colonic torsion that resolved after fluid resuscitation and restoration of myocardial perfusion. CASE PRESENTATION: An 11-year-old, male neutered mixed breed dog presented with a one day history of vomiting, tenesmus, and lethargy. Physical examination identified an irregular heart rhythm and intermittent pulse deficits. A ventricular arrhythmia represented by ventricular premature complexes (VPCs) organized in bigeminy, was appreciated on a 3-lead electrocardiogram (ECG) with a single lead (II) view. Abdominal radiographs confirmed a colonic torsion. Prior to anesthetic induction, ventricular bigeminy was non responsive to fentanyl or lidocaine. The patient was anesthetized and intravascular volume deficit was identified by dampened plethysmographic wave amplitude (plethysomographic variability), audible softening of the Doppler sound, and more pronounced pulse deficits. Fluid resuscitation was achieved with a combination of intravenous crystalloid and colloid fluid therapy comprising 7.2% hypertonic saline and 6% hetastarch. The patient's cardiac rhythm converted to normal sinus after fluid resuscitation. The colonic torsion was surgically corrected. The patient recovered well from anesthesia and was ultimately discharged from the hospital 5 days later. CONCLUSIONS: The present case report highlights that myocardial ischemia can lead to ventricular arrythmias, such as ventricular bigeminy. This is the first documented case of ventricular bigeminy in the canine patient with a colonic torsion. Assessment of patient volume status and appropriate fluid resuscitation along with continuous electrocardiogram (ECG) monitoring are vital to patient stability under general anesthesia.

Evaluating a communication aid for return of genetic results in families with hypertrophic cardiomyopathy: A randomized controlled trial.

Genetic testing for hypertrophic cardiomyopathy (HCM) is considered a key aspect of management. Communication of genetic test results to the proband and their family members, can be a barrier to effective uptake. We hypothesized that a communication aid would facilitate effective communication, and sought to evaluate knowledge and communication of HCM risk to at-risk relatives. This was a prospective randomized controlled trial. Consecutive HCM patients attending a specialized clinic, who agreed to participate, were randomized to the intervention or current clinical practice. The intervention consisted of a genetic counselor-led appointment, separate to their clinical cardiology review, and guided by a communication booklet which could be written in and taken home. Current clinical practice was defined as the return of the genetic result by a genetic counselor and cardiologist, often as part of a clinical cardiology review. The primary outcome was the ability and confidence of the individual to communicate genetic results to at-risk relatives. The a priori outcome of improved communication among HCM families did not show statistically significant differences between the control and intervention group, though the majority of probands in the intervention group achieved fair communication (n = 13/22) and had higher genetic knowledge scores than those in the control group (7 ± 3 versus 6 ± 3). A total of 29% of at-risk relatives were not informed of a genetic result in their family. Communication among HCM families remains challenging, with nearly a third of at-risk relatives not informed of a genetic result. We show a significant gap in the current approach to supporting family communication about genetics. Australian New Zealand Clinical Trials Registry: ACTRN12617000706370.

Sudden cardiac death in the young: A qualitative study of experiences of family members with cardiogenetic evaluation.

Sudden cardiac death (SCD) is a devastating event for the family and the community, especially when it occurs in a young person (<45 years). Genetic heart diseases, including cardiomyopathies and primary arrhythmia syndromes, are an important cause of SCD in the young. Although cardiogenetic evaluation, that is, clinical evaluation, genetic testing, and psychological support, is increasingly performed after SCD, it is unknown how suddenly bereaved family members experience the process. We aimed to explore the experiences of family members with cardiogenetic evaluation after SCD, and their perception of the process and care received. In-depth interviews were conducted with 18 family members of young people (<45 years old) who died suddenly, including parents, siblings, and partners. The interviews were thematically analyzed by two researchers independently. In total, 18 interviews were conducted from 17 families. The following themes were identified: (1) Experiences with postmortem genetic testing including managing expectations and psychological impact, (2) appreciation of care such as access to genetic counseling and relief following cardiac evaluation of relatives, and (3) need for support including unmet psychological support needs and better coordination of care immediately after the death. Although participants appreciated the opportunity for cardiogenetic evaluation, they also experienced a lack of coordination of cardiogenetic and psychological care. Our findings stress the importance of access to expert multidisciplinary teams, including psychological care, to adequately support these families after a SCD in a young family member.

Chemotherapy-related cardiotoxicity: are Australian practitioners missing the point?

BACKGROUND: It has long been established that cardiotoxicity occurs as a result of exposure to certain chemotherapeutics, particularly anthracyclines. Historically, clinicians equate cardiotoxicity with a poor prognosis, in a small percentage of patients and deem long-term surveillance as optional. Emerging evidence suggests that anthracycline cardiotoxicity (ACT) is a life-long risk with an incidence approaching 20%. AIMS: To elucidate the incidence of anthracycline cardiotoxicity within a current paediatric oncology survivor cohort. METHODS: Participants were identified through the Haematology-Oncology database at the Royal Children's Hospital, Melbourne. Patients were identified from a retrospective audit of outpatient attendances between January 2008 and December 2015. Patients with a cancer diagnosis exposed to anthracyclines were eligible for the study. Patient demographics and echocardiogram findings were recorded with patients subcategorised according to degree of ACT. More significant ACT defined as fractional shortening (FS) <24% and less significant if FS 24-28% or a decline in baseline ejection fraction of >10%. RESULTS: Two hundred and eighty-six of a total 481 identified patients were eligible for study inclusion. Twenty patients displayed significant ACT with FS <24%. Ten patients had a FS 24-28% and 25 patients with a decline in ejection fraction from baseline of >10%. Overall, 6.6% demonstrated significant cardiac complications, whilst 19.6 % demonstrated some degree of ACT and decline in myocardial function. When stratified for cumulative anthracycline dose, the incidence of severe cardiac dysfunction was 5.1% (<250 mg/m2 ) and 25% (>250 mg/m2 ) CONCLUSION: This study demonstrates, in keeping with modern literature, the higher incidence of anthracycline associated cardiac toxicity and a need for better surveillance and follow up.

Factors influencing uptake of familial long QT syndrome genetic testing.

Ongoing challenges of clinical assessment of long QT syndrome (LQTS) highlight the importance of genetic testing in the diagnosis of asymptomatic at-risk family members. Effective access, uptake, and communication of genetic testing are critical for comprehensive cascade family screening and prevention of disease complications such as sudden cardiac death. The aim of this study was to describe factors influencing uptake of LQTS genetic testing, including those relating to access and family communication. We show those who access genetic testing are overrepresented by the socioeconomically advantaged, and that although overall family communication is good, there are some important barriers to be addressed. There were 75 participants (aged 18 years or more, with a clinical and/or genetic diagnosis of LQTS; response rate 71%) who completed a survey including a number of validated scales; demographics; and questions about access, uptake, and communication. Mean age of participants was 46 ± 16 years, 20 (27%) were males and 60 (80%) had genetic testing with a causative gene mutation in 42 (70%). Overall uptake of cascade testing within families was 60% after 4 years from proband genetic diagnosis. All participants reported at least one first-degree relative had been informed of their risk, whereas six (10%) reported at least one first-degree relative had not been informed. Those who were anxious or depressed were more likely to perceive barriers to communicating. Genetic testing is a key aspect of care in LQTS families and intervention strategies that aim to improve equity in access and facilitate effective family communication are needed.

REACHing for divergence?-UK chemical regulation post-Brexit.

On 1 January 2021, the United Kingdom formally exited the European Union (EU; Brexit) and ceased to be subject to EU chemical regulation requirements. Before Brexit, UK chemical policy was regulated largely by the EU. With its large internal market, sophisticated regulatory capability, and stringent regulatory framework, the EU has become the world's leading regulatory state, regularly influencing global industrial decisions and practices. At the time of writing, there has been limited academic analysis of the implications of Brexit for UK chemical regulation. More than two years post-Brexit, we have the opportunity to assess UK chemical regulation and revisit early expectations about regulatory divergence. This article takes the EU's Regulation on the Registration, Evaluation, Authorisation, and Restriction of Chemicals (REACH) as a case study to analyze patterns of post-Brexit regulatory divergence, thereby providing one of the first analyses of the implications of Brexit on UK chemical regulation. Through the analysis and review of key documents and reports (n = 99), this article assesses the extent to which UK and EU regulatory (REACH) regimes are beginning to diverge and discusses the potential implications of any divergence for the United Kingdom. We find that the UK and EU chemical regulatory regimes are now evolving independently and provide clear, empirical evidence of an emerging divergence in regulatory decisions, ambitions, and approaches. The evidence suggests that the United Kingdom is currently unable to keep pace with EU developments, lacking the capacity, expertise, and capability of its EU counterparts, raising the prospect of further divergence in the future. Integr Environ Assess Manag 2024;20:1529-1538. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Approach to the paediatric patient with suspected pheochromocytoma or paraganglioma versus neuroblastoma.

Catecholamine producing tumours of childhood include neuroblastic tumours, phaeochromocytoma and paraganglioma (PPGL). PPGL and neuroblastic tumours can arise in similar anatomical locations and clinical presentations can overlap resulting in diagnostic challenges. Distinguishing between these tumour types is critical as management and long-term surveillance strategies differ depending on the diagnosis. Herein we describe two clinical cases and illustrate key considerations in the diagnostic work up of a neuroblastoma versus PPGL for patients presenting with adrenal, pelvic, and retroperitoneal masses in childhood.

Benefits for children with suspected cancer from routine whole-genome sequencing.

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.

The effect of adding a heated humidified breathing circuit on body temperature in healthy anesthetized dogs.

OBJECTIVE: To compare the effect of a circulating warm water blanket (WWB) in combination with a heated humidified breathing circuit (HHBC) heated to 45 °C on rectal temperature (RT) in dogs undergoing general anesthesia for elective ovariohysterectomies. ANIMALS: 29 healthy dogs. PROCEDURES: Dogs in the experimental group (n = 8) and dogs in the control group (21) were connected to an HHBC and a conventional rebreathing circuit, respectively. All dogs were placed on a WWB in the operating room (OR). The RT was recorded at baseline, premedication, induction, transfer to OR, every 15 minutes during maintenance of anesthesia, and extubation. Incidence of hypothermia (RT < 37 °C) at extubation was recorded. Data were analyzed using unpaired t tests, the Fisher exact test, and mixed-effect ANOVA. Statistical significance was defined as P < .05. RESULTS: There was no difference in RT during baseline, premedication, induction, and transfer to OR. The overall RT was higher for the HHBC group during anesthesia (P = .005) and at extubation (37.7 ± 0.6 °C) compared with the control group (36.6 ± 1.0 °C; P = .006). The incidence of hypothermia at extubation was 12.5% for the HHBC group and 66.7% for the control group (P = .014). CLINICAL RELEVANCE: The combination of HHBC and WWB can reduce the incidence of postanesthetic hypothermia in dogs. Use of an HHBC should be considered in veterinary patients.

Rocuronium-neuromuscular blockade does not influence the patient state index in anesthetized dogs.

OBJECTIVE: To evaluate the effects of rocuronium and sugammadex on the patient state index (PSI) in dogs anesthetized with propofol. ANIMALS: 6 intact healthy male Beagles. PROCEDURES: Anesthesia was induced with and maintained on a propofol infusion. The estimated plasma propofol concentration (ePC) was recorded. Baseline PSI and train-of-four ratio (TOFR) readings were collected for 2 minutes in stable general anesthesia. Neuromuscular blockade (NMB) was induced with 0.6 mg/kg, IV, rocuronium, and full NMB was confirmed with a TOFR of 0. After 5 minutes, the neuromuscular function was restored with 4 mg/kg sugammadex, IV (reversal), and monitored for 5 minutes. Throughout the data collection, ePC, PSI, and TOFR were recorded every 15 seconds and compared with mixed-effect ANOVA. RESULTS: Baseline ePC, PSI, and TOFR were 3.63 ± 0.38, 41 ± 6, and 0.97 ± 0.08 µg/mL, respectively. There was no difference between the baseline of ePC and PSI from NMB or reversal. Compared to the baseline, the TOFR decreased to 0 with NMB (P < .001) and returned to 0.96 ± 0.08 (P = .721) on reversal. After 5 minutes, sugammadex fully reversed 5 out of 6 dogs to TOFR > 0.90 and partially reversed 1 animal to TOFR = 0.80. CLINICAL RELEVANCE: There was no evidence that NMB with rocuronium and sugammadex-induced reversal interfered with PSI readings under steady-state total intravenous anesthesia with propofol. Further evaluation of PSI is warranted to assess its utility in a clinical population to detect changes in levels of consciousness during NMB.

The burden of splice-disrupting variants in inherited heart disease and unexplained sudden cardiac death.

There is an incomplete understanding of the burden of splice-disrupting variants in definitively associated inherited heart disease genes and whether these genes can amplify from blood RNA to support functional confirmation of splicing outcomes. We performed burden testing of rare splice-disrupting variants in people with inherited heart disease and sudden unexplained death compared to 125,748 population controls. ClinGen definitively disease-associated inherited heart disease genes were amplified using RNA extracted from fresh blood, derived cardiomyocytes, and myectomy tissue. Variants were functionally assessed and classified for pathogenicity. We found 88 in silico-predicted splice-disrupting variants in 128 out of 1242 (10.3%) unrelated participants. There was an excess burden of splice-disrupting variants in PKP2 (5.9%), FLNC (2.7%), TTN (2.8%), MYBPC3 (8.2%) and MYH7 (1.3%), in distinct cardiomyopathy subtypes, and KCNQ1 (3.6%) in long QT syndrome. Blood RNA supported the amplification of 21 out of 31 definitive disease-associated inherited heart disease genes. Our functional studies confirmed altered splicing in six variants. Eleven variants of uncertain significance were reclassified as likely pathogenic based on functional studies and six were used for cascade genetic testing in 12 family members. Our study highlights that splice-disrupting variants are a significant cause of inherited heart disease, and that analysis of blood RNA confirms splicing outcomes and supports variant pathogenicity classification.

Post-anesthetic CPS and EQUUS-FAP scores in surgical and non-surgical equine patients: an observational study.

Background: Equine pain scoring may be affected by the residual effect of anesthetic drugs. Objectives: To compare pain scores in the hours immediately following anesthetic recovery to baseline pre-anesthetic scores in equine patients undergoing surgical and non-surgical procedures. Study design: Clinical observational study. Methods: Fifty adult horses undergoing anesthesia for surgical or non-surgical procedures were enrolled. Horses underwent pain scoring using the Composite Pain Score (CPS) and Equine Utrecht University Scale for Facial Assessment of Pain (EQUUS-FAP) prior to anesthesia (T0) and following anesthetic recovery to standing, every hour for 5 h (T1-T5). Data were analyzed using a generalized linear mixed effects model. A post-hoc Dunnett's test for multiple comparisons was performed for variables where an effect was detected. Results: Mean (95% confidence interval) CPS scores for T0-T5 were 1.6 (1.2-2.0), 6.8 (6.0-7.6), 5.1 (4.3-5.9), 4.3 (3.4-5.2), 3.7 (2.8-4.6), and 2.8 (2.0-3.6) and EQUUS-FAP scores were 0.6 (0.3-0.9), 3.0 (2.5-3.5), 1.9 (1.6-2.2), 1.1 (0.8-1.4), 0.6 (0.4-0.8), and 0.7 (0.4-1.0), respectively. For the CPS, scores greater than 5, and for the EQUUS-FAP scores greater than 3, are consistent with minor pain. There was no effect of type of procedure (surgical vs non-surgical) on CPS or EQUUS-FAP scores. There was an effect of time with CPS scores significantly greater than baseline at T1-T5 and EQUUS-FAP scores significantly greater than baseline at T1 and T2. Main limitations: Discomfort caused by hoisting was not quantified and it was difficult to ascertain if this affected the results. Conclusions: Post-anesthetic pain scores may be influenced by the residual effect of anesthetic agents for as long as 5 h and 2 h for the CPS and EQUUS-FAP, respectively.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.

Decision-making and experiences of preimplantation genetic diagnosis in inherited heart diseases: a qualitative study.

Preimplantation genetic diagnosis (PGD) ensures a disease-causing variant is not passed to the next generation, including for inherited heart diseases. PGD is known to cause significant emotional burden, but little is known about how parents experience PGD to select against inherited heart disease. We aim to understand how people with inherited heart disease, and their partners, experience and make decisions about PGD. Participants were recruited from a specialised inherited heart disease clinic. Qualitative semi-structured interviews were conducted with adult participants who had considered PGD. A semi-structured interview schedule explored overall experiences and reasons for undergoing PGD. Broad topics included experience of disease, reproductive history, psychosocial and financial considerations. Interviews were recorded, transcribed verbatim and thematically analysed using a framework method. Twenty participants were included (15 with inherited cardiomyopathy, 3 with inherited arrhythmia syndrome and 2 partners). In contemplating PGD, participants considered 3 main issues: past experience of disease e.g. sudden cardiac death, sport restrictions and clinical heterogeneity; intergenerational responsibilities; and practical considerations such as finances and maternal age. Among those who chose to undergo PGD (n = 7/18), past experience of a significant cardiac event, such as family history of sudden cardiac death, was important in the decision process. The decision to undergo PGD for inherited heart disease is complex and influenced by individual values and experience of disease. We highlight key areas where further discussion may assist in PGD decision processes.

A flexible endotracheal tube introducer improves first-attempt success of intubation in cats by novice anesthetists.

OBJECTIVE: To test whether the use of a flexible endotracheal tube introducer (ETI) facilitates intubation of cats by veterinary students with little or no experience. ANIMALS: 125 healthy cats. PROCEDURES: Cats were sedated with dexmedetomidine and morphine IM, and anesthesia was induced with propofol. They were randomly assigned to be intubated by supervised veterinary students using an ETI within a tracheal tube or an endotracheal tube alone (3.0, 3.5, or 4.0 internal diameter sizes). Success rate at first attempt, number of attempts to intubate (up to 3), and time to intubate were recorded. Multivariate logistic regression was used to test associations between several factors such as use of an ETI, cat's weight, endotracheal tube size, administration of ketamine for sedation, and first-attempt success. Significance was considered when P < 0.05. RESULTS: Success rate for the first attempt was higher with an ETI (79% [51/64) than without it (46% [28/61]), and attempts to intubate were fewer when an ETI was used (both P < 0.001). Time to intubate did not differ between groups (ETI, 30 seconds [4 to 143 seconds]; endotracheal tube, 28 seconds [5 to 180 seconds]). Use of an ETI was positively associated with improved first-attempt success, and the 3.0-mm internal diameter of the tube was negatively associated (both P ≤ 0.001). CLINICAL RELEVANCE: The use of a flexible ETI improved the success of first-attempt intubation of cats by veterinary students. This technique may help minimize the number of attempts during intubation and incidence of complications that could arise from multiple attempts.

The role of genetic testing in diagnosis and care of inherited cardiac conditions in a specialised multidisciplinary clinic.

BACKGROUND: The diagnostic yield of genetic testing for inherited cardiac diseases is up to 40% and is primarily indicated for screening of at-risk relatives. Here, we evaluate the role of genomics in diagnosis and management among consecutive individuals attending a specialised clinic and identify those with the highest likelihood of having a monogenic disease. METHODS: A retrospective audit of 1697 consecutive, unrelated probands referred to a specialised, multidisciplinary clinic between 2002 and 2020 was performed. A concordant clinical and genetic diagnosis was considered solved. Cases were classified as likely monogenic based on a score comprising a positive family history, young age at onset, and severe phenotype, whereas low-scoring cases were considered to have a likely complex aetiology. The impact of a genetic diagnosis was evaluated. RESULTS: A total of 888 probands fulfilled the inclusion criteria, and genetic testing identified likely pathogenic or pathogenic (LP/P) variants in 330 individuals (37%) and suspicious variants of uncertain significance (VUS) in 73 (8%). Research-focused efforts identified 46 (5%) variants, missed by conventional genetic testing. Where a variant was identified, this changed or clarified the final diagnosis in a clinically useful way for 51 (13%). The yield of suspicious VUS across ancestry groups ranged from 15 to 20%, compared to only 10% among Europeans. Even when the clinical diagnosis was uncertain, those with the most monogenic disease features had the greatest diagnostic yield from genetic testing. CONCLUSIONS: Research-focused efforts can increase the diagnostic yield by up to 5%. Where a variant is identified, this will have clinical utility beyond family screening in 13%. We demonstrate the value of genomics in reaching an overall diagnosis and highlight inequities based on ancestry. Acknowledging our incomplete understanding of disease phenotypes, we propose a framework for prioritising likely monogenic cases to solve their underlying cause of disease.

Clinical Profile and Health Disparities in a Multiethnic Cohort of Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Clinical studies of hypertrophic cardiomyopathy are over-represented by individuals of European ethnicity, with less known about other ethnic groups. We investigated differences between patients in a multiethnic Australian hypertrophic cardiomyopathy population. METHODS: We performed a retrospective cohort study of 836 unrelated hypertrophic cardiomyopathy probands attending a specialized clinic between 2002 and 2020. Major ethnic groups were European (n=611), East Asian (n=75), South Asian (n=58), and Middle Eastern and North African (n=68). The minor ethnicity groups were Oceanian (n=9), People of the Americas (n=7), and African (n=8). One-way ANOVA with Dunnett post hoc test and Bonferroni adjustment were performed. RESULTS: Mean age of the major ethnic groups was 54.9±16.9 years, and 527 (65%) were male. Using the European group as the control, East Asian patients had a lower body mass index (29 versus 25 kg/m2, P<0.0001). South Asians had a lower prevalence of atrial fibrillation (10% versus 31%, P=0.024). East Asians were more likely to have apical hypertrophy (23% versus 6%, P<0.0001) and Middle Eastern and North African patients more likely to present with left ventricular outflow tract obstruction (46% versus 34%, P=0.0003). East Asians were less likely to undergo genetic testing (55% versus 85%, P<0.0001) or have an implantable cardioverter-defibrillator implanted (19% versus 36%, P=0.037). East Asians were more likely to have a causative variant in a gene other than MYBPC3 or MYH7, whereas Middle Eastern and North African and South Asians had the highest rates of variants of uncertain significance (27% and 21%, P<0.0001). CONCLUSIONS: There are few clinical differences based on ethnicity, but importantly, we identify health disparities relating to access to genetic testing and implantable cardioverter-defibrillator use. Unless addressed, these gaps will likely widen as we move towards precision-medicine-based care of individuals with hypertrophic cardiomyopathy.

Malignant Melanoma in Children and Adolescents Treated in Pediatric Oncology Centers: An Australian and New Zealand Children's Oncology Group (ANZCHOG) Study.

OBJECTIVES: Unlike adults, malignant melanoma in children and adolescents is rare. In adult melanoma, significant progress in understanding tumor biology and new treatments, including targeted therapies and immunotherapy have markedly improved overall survival. In sharp contrast, there is a paucity of data on the biology and clinical behavior of pediatric melanoma. We report a national case series of all pediatric and adolescent malignant melanoma presenting to ANZCHOG Childhood Cancer Centers in Australia and New Zealand. METHODS: A retrospective, descriptive, multi-center study was undertaken to identify patients less than 18 years of age treated for cutaneous malignant melanoma over a twenty-year period (1994 to 2014). Data on clinical characteristics, histopathology, and extent of disease, treatment and follow-up are described. RESULTS: A total of 37 cases of malignant melanoma were identified from all of the Australasian tertiary Childhood Cancer Centers. The median age was 10 years (range 1 month - 17 years). Clinically, the most common type of lesion was pigmented, occurring in sixteen (57%) patients, whilst amelanotic was seen in 7 patients (25%). In 11 (27.9%) the Breslow thickness was greater than 4mm. A total of 11 (29.7%) patients relapsed and 90% of these died of disease. Five-year event free survival (EFS) and overall survival were 63.2 (95% CI: 40.6 - 79.1) and 67.7% (95% CI: 45.1 - 82.6) respectively. CONCLUSION: Our data confirms that melanoma is a rare presentation of cancer to tertiary Australasian Childhood Cancer Centers with only 37 cases identified over two decades. Notably, melanoma managed in Childhood Cancer Centers is frequently at an advanced stage, with a high percentage of patients relapsing and the majority of these patients who relapsed died of disease. This study confirms previous clinical and prognostic information to support the early multidisciplinary management in Childhood Cancer Centers, in conjunction with expert adult melanoma centers, of this rare and challenging patient group.

The Effects of Frequency and Duration of Handling on the Development of Feline Upper Respiratory Infections in a Shelter Setting.

Reducing stress is important to maintaining the health of shelter cats and decreasing the risk of upper respiratory disease (URD). The aim of this study was to determine if the frequency and/or duration of daily routine handling of shelter cats affects the likelihood of URD development. At a closed admission shelter, each cat free of URD on intake was given a cage card for recording handling data. These data included: date and times when the cat was handled, duration of handling, if and when the cat developed signs of URD, and the handler identity. Cox regression was used to determine the relationship between these factors and URD development. We found cats that did not develop URD were handled significantly more than cats that did (1.1 times per day vs. 0.7 times per day, p < 0.001). Increased frequency of handling had a borderline significant effect on the hazard of developing URD (HR 0.37; CI: 0.13-1.1; p = 0.066). No other parameters were significantly associated with the development of URD; however, small sample size may be responsible for this finding. A larger study is needed to elucidate the relationship between handling and URD development.

Retrospective evaluation of outpatient canine parvovirus treatment in a shelter-based low-cost urban clinic.

OBJECTIVE: To evaluate survival and associated risk factors when utilizing an outpatient treatment protocol for treatment of canine parvovirus (CPV) performed in a shelter-based low-cost urban clinic. DESIGN: Retrospective study. SETTING: Pennsylvania Society for the Prevention of Cruelty to Animals. ANIMALS: Ninety-five CPV positive dogs presented between June 1 and July 31, 2016. Owners elected for outpatient care when inpatient care was not financially feasible and the dog was considered medically stable for outpatient care. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 95 CPV positive dogs, 79 (83%) survived treatment. Logistic regression indicated that an increasing number of days with clinical signs prior to treatment and an increase in percent body weight during treatment were significantly associated with survival (odds ratio [OR], 3.15, P = 0.020; and OR, 1.29, P = 0.027, respectively). Hypothermia upon presentation (T < 37℃) was negatively associated with survival (OR, 0.002; P = 0.002). CONCLUSIONS AND CLINICAL RELEVANCE: The survival rate of this clinic suggests that an outpatient program may be a potential alternative treatment to inpatient care. Longer duration of clinical signs prior to treatment and an increase in percent body weight during treatment appear to be associated with increased survival outcomes, while hypothermia on presentation appears to be associated with decreased survival outcomes.