Lessons learnt in the first year of an Australian pediatric cardio oncology clinic.

BACKGROUND: Modern oncological therapies together with chemotherapy and radiotherapy have broadened the agents that can cause cardiac sequelae, which can manifest for pediatric oncology patients while on active treatment. Recommendations for high-risk patients who should be monitored in a pediatric cardio-oncology clinic have previously been developed by expert Delphi consensus by our group. In 2022 we opened our first multidisciplinary pediatric cardio-oncology clinic adhering to these recommendations in surveillance and management. OBJECTIVES: Our pediatric cardio-oncology clinic aimed to: (i) Document cardiovascular toxicities observed within a pediatric cardio-oncology clinic and. (ii) Evaluate the applicability of the Australian and New Zealand Pediatric Cardio-Oncology recommendations. METHODS: Monthly multidisciplinary cardio-oncology clinics were conducted in an Australian tertiary pediatric hospital. Structured standardised approaches to assessment were built into the electronic medical record (EMR). All patients underwent baseline echocardiogram and electrocardiogram assessment together with vital signs in conjunction with standard history and examination. RESULTS: Nineteen (54%) individuals had a documented cardiovascular toxicity or pre-existing risk factor prior to referral. The two most common cardiovascular toxicities documented during clinic review included Left Ventricular Dysfunction (LVD) and hypertension. Of note 3 (8.1%) patients had CTCAE grade III LVD. An additional 10 (27%) patients reviewed in clinic had CTCAE grade I hypertension. None of these patients had hypertension noted within their referral. Cascade testing for cardiac history was warranted in 2 (5.4%) of patients. CONCLUSIONS: Pediatric cardio-oncology clinics are likely beneficial to documenting previously unrecognised cardiotoxicity and relevant cardiac family histories, whilst providing an opportunity to address lifestyle risk factors.

Infections in children following chimeric antigen receptor T-cell therapy for B-cell acute lymphoblastic leukemia.

BACKGROUND: CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy is transforming care for pediatric patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). There are limited pediatric-specific data concerning the infection risks associated with CD19 CAR-T therapy and the adequacy of current antimicrobial prophylaxis guidelines for these patients. METHODS: We describe the antimicrobial prophylaxis used and the types of infectious occurring in the first 100 days following CAR-T therapy for relapsed or refractory B-cell ALL in children and adolescents (≤18 years) at our centre. RESULTS: Twenty-seven patients received their first CAR-T infusion (CTI) during the study period. Almost all patients (96%) had a comprehensive Infectious Diseases review prior to CTI, which informed a personalised prophylaxis or fever/sepsis plan in six (22%). Overall, six (22%) patients had one or more infections during the study period including five (19%, 0.9 per 100 days-at-risk) from days 0-30 and three (n = 20, 15%, 0.6 per 100 days-at-risk) from days 31-100. Bacterial blood stream infections were the most common type of infection encountered during both time periods, and one patient had probable pulmonary aspergillosis. There were no infection-related deaths. CONCLUSION: Our study contributes important information on the spectrum of infections encountered in pediatric patients with B-ALL post CAR-T therapy. Overall, the burden of infectious complications post CAR-T therapy in our cohort is lower than previously reported in the literature. Results suggest that our prophylaxis recommendations are effective in this population.

Estrés académico en estudiantes de Medicina durante la pandemia de covid-19 / Academic stress in Medicine students during covid-19 pandemic i: en

Introducción: Los estudiantes de las ciencias médicas refieren mayores niveles de estrés académico, particularmente los de la carrera de Medicina. Objetivo: Caracterizar a estudiantes de Medicina según nivel de estrés, reacciones psicosomáticas y estrategias de afrontamiento usadas durante la pandemia de covid-19. Métodos: Se realizó un estudio descriptivo y transversal, desde septiembre hasta diciembre del 2020, de 30 estudiantes de primer y segundo años de la carrera de Medicina, pertenecientes a la Facultad No. 2 de la Universidad de Ciencias Médicas de Santiago de Cuba, que refirieron sentirse nerviosos. Como variables analizadas figuraron: sexo, nivel de estrés autopercibido, situaciones generadoras de estrés, reacciones físicas, psicológicas, comportamentales, y estrategias de afrontamiento. Se utilizó el porcentaje para los datos cualitativos, así como la media y la desviación estándar para los cuantitativos. Resultados: El nivel de estrés autopercibido resultó medio en el sexo masculino y alto en el femenino. En el estudio predominaron el tiempo limitado para la realización de trabajos, las evaluaciones de los profesores y la sobrecarga académica como situaciones generadoras de estrés; la somnolencia, la inquietud, el aislamiento y los conflictos o discusiones como principales reacciones; la planificación de sus tareas, la búsqueda de información sobre la situación y la habilidad asertiva como estrategias de afrontamiento. Conclusiones: La muestra estudiada se caracterizó por presentar nivel medio de estrés autopercibido, responder a situaciones generadoras de estrés académico, expresar reacciones físicas, psicológicas y comportamentales ante estas situaciones, así como también por usar estrategias de afrontamiento centradas en el problema.

Introduction: Medical sciences students refer higher levels of academic stress, particularly those of the Medicine career. Objective: To characterize Medicine students according to stress level, psychosomatic reactions and confrontation strategies used during covid-19 pandemic. Methods: A descriptive and cross-sectional study was carried out from September to December, 2020, of 30 first and second year students of the Medicine career, belonging to Faculty No. 2 of the University of Medical Sciences in Santiago de Cuba that referred to feel nervous. The analyzed variables were sex, self-perceived level of stress, situations generating stress, physical, psychological, behavioural reactions and confrontation strategies. The percentage was used for the qualitative data, as well as the mean and the standard deviation for the quantitative ones. Results: The self-perceived level of stress was average in the male sex and high in the female sex. In the study there was a prevalence of the limited time for the realization of works, evaluations of professors and academic overload as situations generating stress; the drowsiness, restlessness, isolation and conflicts or discussions as main reactions; planning of their tasks, search of information on the situation and assertive skill as confrontation strategies. Conclusions: The studied sample was characterized by presenting a medium level of self-perceived stress, responding to situations that generate academic stress, expressing physical, psychological and behavioural reactions when facing these situations, as well as using confrontation strategies focused on the problem.

Density of antibiotic use and infectious complications in pediatric allogeneic hematopoietic cell transplantation.

BACKGROUND: Antibiotics, while an essential component of supportive care in allogeneic hematopoietic cell transplantation (allo-HCT), can have adverse effects and select for antibiotic resistance. Understanding of patterns of use will inform antimicrobial stewardship (AMS) interventions. METHODS: Retrospective, single-center cohort of children undergoing first allo-HCT (n = 125). Antibiotic prescription and infection data were included from the date conditioning was commenced until 30 days post allo-HCT. Antibiotic use was reported as length of therapy (LOT) (number of days a patient received an antibiotic) and days of therapy DOT (aggregating all antibiotics prescribed per day). Infections were classified as microbiologically documented infection (MDI) or clinically documented infections. RESULTS: At least one course of antibiotics was administered to 124 (99%) patients. The LOT was 636 per 1000 patient days and DOT was 959 per 1000 patient days. The median duration of cumulative antibiotic exposure per patient was 24 days (interquartile range [IQR] 20-30 days). There were 131 days of fever per 1000 patient days with patients febrile for a median of 4 days (IQR 1-7 days). Piperacillin-tazobactam was used for 116 (94%) of patients with an LOT of 532 per 1000 patient days. A total of 119 MDI episodes occurred in 74 (59%) patients, including blood stream infection in 30 (24%) and a proven/probable invasive fungal infection in 4 (3%). CONCLUSION: Pediatric HCT patients receive prolonged courses of broad-spectrum antibiotics relative to the frequency of fever and bacterial infections. This study has identified opportunities for AMS intervention to improve outcomes for our HCT patients.

Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia.

5-year overall survival rates have surpassed 90% for childhood acute lymphocytic leukaemia, but survivors are at risk for permanent health sequelae. Although event-free survival appropriately represents the outcome for cancers with poor overall survival, this metric is inadequate when cure rates are high but challenged by serious, persistent complications. Accordingly, a group of experts in paediatric haematology-oncology, representative of 17 international acute lymphocytic leukaemia study groups, launched an initiative to construct a measure, designated severe toxicity-free survival (STFS), to quantify the occurrence of physician-prioritised toxicities to be integrated with standard cancer outcome reporting. Five generic inclusion criteria (not present before cancer diagnosis, symptomatic, objectifiable, of unacceptable severity, permanent, or requiring unacceptable treatments) were used to assess 855 health conditions, which resulted in inclusion of 21 severe toxicities. Consensus definitions were reached through a modified Delphi process supplemented by two additional plenary meetings. The 21 severe toxicities include severe adverse health conditions that substantially affect activities of daily living and are refractory to therapy (eg, refractory seizures), are without therapeutic options (eg, blindness), or require substantially invasive treatment (eg, cardiac transplantation). Incorporation of STFS assessment into clinical trials has the potential to improve and diversify treatment strategies, focusing not only on traditional outcome events and overall survival but also the frequencies of the most severe toxicities. The two major aims of this Review were to: prioritise and define unacceptable long-term toxicity for patients with childhood acute lymphocytic leukaemia, and define how these toxicities should be combined into a composite quantity to be integrated with other reported outcomes. Although STFS quantifies the clinically unacceptable health tradeoff for cure using childhood acute lymphocytic leukaemia as a model disease, the prioritised severe toxicities are based on generic considerations of relevance to any other cancer diagnosis and age group.

The Australia and New Zealand Cardio-Oncology Registry: evaluation of chemotherapy-related cardiotoxicity in a national cohort of paediatric cancer patients.

Cancer therapy related cardiac dysfunction (CTRCD) is an area of increasing focus, particularly during the survivorship period, for paediatric, adolescent and adult cancer survivors. With the advent of immunotherapy and targeted therapy, there is a new set of mechanisms from which paediatric and young adult patients with cancer may suffer cardiovascular injury. Furthermore, cardiovascular disease is the leading cause of morbidity and mortality in the survivorship period. The recently established Australian Cardio-Oncology Registry is the largest and only population-based cardiotoxicity database of paediatric and adolescent and young adult oncology patients in the world, and the first paediatric registry that will document cardiotoxicity caused by chemotherapy and novel targeted therapies using a prospective approach. The database is designed for comprehensive data collection and evaluation of the Australian practice in terms of diagnosis and management of CTRCD. Using the Australian Cardio-Oncology Registry critical clinical information will be collected regarding predisposing factors for the development of CTRCD, the rate of subclinical left ventricular dysfunction and transition to overt heart failure, further research into protectant molecules against cardiac dysfunction and aid in the discovery of which genetic variants predispose to CTRCD. A health economic arm of the study will assess the cost/benefit of both the registry and cardio-oncology clinical implementation. Finally, an imaging arm will establish if exercise cardiac magnetic resonance imaging and VO2 max testing is a more sensitive predictor of cardiac reserve in paediatric and adolescent and young adult oncology patients exposed to cardiac toxic therapies.

Caracterización clínico epidemiológica de niños con sospecha de la COVID-19 en el Hospital Universitario de Caracas

El primer caso por la COVID-19 en niños se confirmó en China, el 20 de enero de 2020, con características distintas en comparación con los adultos. Se analizaron las características de los pacientes pediátricos con diagnóstico de caso sospechoso de la COVID-19, atendidos en el triaje de Infectología Pediátrica del Hospital Universitario de Caracas (HUC), desde marzo hasta octubre del 2020. Estudio observacional, transversal, retrospectivo, descriptivo, se recabaron datos demográficos, cuadro clínico, paraclínicos, tratamiento indicado y evolución. Los datos fueron analizados mediante frecuencia y porcentaje para datos cualitativos y media y desviación estándar para los cuantitativos. Se revisaron 455 historias, 176 cumplieron criterios de inclusión (38,7 %) de casos sospechosos de la COVID-19. El 51,1 % (n=90) fueron del sexo masculino. Los preescolares correspondieron al 28,9 % (n=51). 75 % (n=132) de los pacientes refieren haberse contagiado en su domicilio. En el 17,6 % (n=31) se logró confirmar el diagnóstico de la COVID-19. Los síntomas más comunes fueron tos, fiebre y rinorrea. No hubo hallazgos estadísticamente significativos con respecto a las pruebas de laboratorio. En la radiografía de tórax se evidenció más frecuentemente el patrón reticular, con distribución bilateral. La tomografía de tórax mostró el patrón reticular en todos los casos. El tratamiento más utilizado fue el sintomático. La evolución de la mayoría de los pacientes fue satisfactoria.

The first case of COVID-19 in children was confirmed in China, on January 20, 2020, with different characteristics compared to adults. The characteristics of pediatric patients diagnosed with a suspected case of COVID-19, treated in the Pediatric Infectology triage of the Hospital Universitario de Caracas (HUC), from March to October 2020, were analyzed. Observational, cross-sectional, retrospective, descriptive study, Demographic data, clinical and paraclinical symptoms, indicated treatment and evolution were collected. Data were analyzed by frequency and percentage for qualitative data and mean and standard deviation for quantitative data. 455 records were reviewed, 176 met the inclusion criteria (38.7 %) of suspected COVID-19 cases. 51.1 % (n = 90) were male. Preschoolers corresponded to 28.9 % (n = 51). 75 % (n = 132) of the patients reported having been infected at home. In 17.6 % (n = 31), the diagnosis of COVID-19 was confirmed. The most common symptoms were cough, fever and rhinorrhea. There were no statistically significant findings regarding laboratory tests. The chest X-ray showed the reticular pattern more frequently, with bilateral distribution. Chest tomography showed the reticular pattern in all cases. The most used treatment was symptomatic. The evolution of most of the patients was satisfactory.

Exercise cardiovascular magnetic resonance reveals reduced cardiac reserve in pediatric cancer survivors with impaired cardiopulmonary fitness.

BACKGROUND: Pediatric cancer survivors are at increased risk of cardiac dysfunction and heart failure. Reduced peak oxygen consumption (peak VO2) is associated with impaired cardiac reserve (defined as the increase in cardiac function from rest to peak exercise) and heart failure risk, but it is unclear whether this relationship exists in pediatric cancer survivors. This study sought to investigate the presence of reduced peak VO2 in pediatric cancer survivors with increased risk of heart failure, and to assess its relationship with resting cardiac function and cardiac haemodynamics and systolic function during exercise. METHODS: Twenty pediatric cancer survivors (8-24 years; 10 male) treated with anthracycline chemotherapy ± radiation underwent cardiopulmonary exercise testing to quantify peak VO2, with a value < 85% of predicted defined as impaired peak VO2. Resting cardiac function was assessed using 2- and 3-dimensional echocardiography, with cardiac reserve quantified from resting and peak exercise heart rate, stroke volume index (SVI) and cardiac index (CI) using exercise cardiovascular magnetic resonance (CMR). RESULTS: Twelve of 20 survivors (60%) had reduced peak VO2 (70 ± 16% vs. 97 ± 14% of age and gender predicted). There were no differences in echocardiographic or CMR measurements of resting cardiac function between survivors with normal or impaired peak VO2. However, those with reduced peak VO2 had diminished cardiac reserve, with a lesser increase in CI and SVI during exercise (Interaction P < 0.01 for both), whilst the heart rate response was similar (P = 0.71). CONCLUSIONS: Whilst exercise intolerance is common among pediatric cancer survivors, it is poorly explained by resting measures of cardiac function. In contrast, impaired exercise capacity is associated with impaired haemodynamics and systolic functional reserve measured during exercise. Consequently, measures of cardiopulmonary fitness and cardiac reserve may aid in early identification of survivors with heightened risk of long-term heart failure.

Adherencia de los profesionales al protocolo de manejo y red de apoyo familiar de sífilis gestacional y congénita / Adhesion of professionals to management protocol and gestational and congenital syphilis family support network / A adesão dos profissionais e gestão de suporte de rede família de protocolos de gestação e sífilis congênita

Objetivo: Determinar la adherencia de los profesionales médicos y de enfermería al protocolo de sífilis congénita y gestacional implementado por el Ministerio de la Protección Social. Materiales y Métodos: Estudio descriptivo longitudinal con una población de 215 gestantes y una muestra de 11 gestantes diagnosticadas con sífilis gestacional en 10 municipios de un departamento en Colombia entre febrero y abril de 2013. Se utilizaron como instrumentos el Familiograma, Faces III (Olson), Lista de chequeo protocolo. Medidas de tendencia central. Participación voluntaria bajo consentimiento informado. Resultados: la media poblacional es de 20 años, baja escolaridad, amas de casa, en unión libre, todas afiliadas a seguridad social. El 60% corresponde a familias nucleares, faces III: 50% familias equilibradas, 30% moderadas y 20% extremas. Protocolo: Una gestante no tuvo control prenatal, el 54,5% no registran factores de riesgo, 60,3% diagnosticadas en tercer trimestre, 36,3% de recién nacidos con sífilis congénita, no se registra seguimiento serológico, no hay registro educativo a la paciente ni a la pareja, no hay valoración de genitales ni piel en examen físico de las gestantes, atención a RN incompleta, tratamiento suministrado adecuado. Conclusiones: Predominio de las familias nucleares y equilibradas, con capacidad de aprender de las crisis. No hay adherencia total al protocolo, no hay seguimiento por parte de los profesionales que brindan atención y cuidado a la usuaria. Se evidencia falta de educación continua en el tema al profesional de enfermería como líder del proceso en la región.

Objective: To determine the adherence of medical and nursing professionals to the protocol of congenital syphilis and gestational implemented by the Ministry for the Protection. Materials and Methods: Descriptive longitudinal study with 215 pregnant population and sample 11 pregnant women diagnosed with gestational syphilis in 10 localities of a state in Colombia between February and April 2013 were used as instruments the"Familiograma", Faces III (Olson) protocol check list. Measures of central tendency. Voluntary participation under informed consent. Results: Population average is 20 years, low education, housewives, married, they have social security. 60% of nuclear families, faces III: 50% balanced families, 30% moderate and 20% extreme. Protocol: One (1) pregnant women had no prenatal care. 54.5% reported no risk factors, diagnostic 60.3% in third quarter, 36.3% newborns with congenital syphilis, no serological monitoring is recorded, no educational record to the patient or partner, no valuation genital skin or physical examination of pregnant women, newborns incomplete care, provided proper treatment. Conclusions: Prevalence of nuclear and balanced families, with ability to learn from crises. No full adherence to the protocol, no monitoring by professionals providing care and attention to the user. Lack of continuing education about the topic to the nurse as leader of the process in the region is evident.

Objetivo: Para determinar a aderência do protocolo médico e de enfermagem da sífiliscongênita e gestacional implementado pelo Ministério para os profissionais de proteção. Materiais e Métodos: Estudo descritivo longitudinal com uma população de 215 grávida e uma amostra de 11 mulheres grávidas diagnosticadas com sífilis gestacionalem 10 municípios de um departamento na Colômbia, entre fevereiro e abril de 2013, foram utilizados como instrumentos a Familiograma, Faces III lista de verificação (Olson) protocolo. Medidas de tendência central. A participação voluntária sob consentimento informado. Resultados: A média da população quer dizer 20 anos, baixa escolaridade, donas de casa, união, todos os filiados para a segurança social. Os 60% é famílias nucleares, enfrenta III: 50% famíliasequilibradas, 30% moderada e 20% extremas. Protocolo: Um as mulheres grávidas não tinha o pré-natal. 54,5% não relataram fatores de risco, diagnósticode 60,3% no terceiro trimestre, 36,3% recém-nascidos com sífilis congênita, semacompanhamento sorológico é registrado, não há registro educacional para o paciente ou do parceiro, sem avaliação pele genital ou no exame físico de mulheres grávidas, recém-nascidos atenção incompleta, desde o tratamento adequado. Conclusões: A prevalencia de nuclear e equilibrada, com capacidade de aprender com as crises familiares. Sem plena adesão ao protocolo, nenhum monitoramento por profissionais que prestam cuidados e atenção para o utente. Falta de educação continuada sobre o assunto para enfermeiro como líder doprocesso na região é evidente

Randomized trial of early bubble continuous positive airway pressure for very low birth weight infants.

OBJECTIVE: To determine whether very low birth weight infants (VLBWIs), initially supported with continuous positive airway pressure (CPAP) and then selectively treated with the INSURE (intubation, surfactant, and extubation to CPAP; CPAP/INSURE) protocol, need less mechanical ventilation than those supported with supplemental oxygen, surfactant, and mechanical ventilation if required (Oxygen/mechanical ventilation [MV]). STUDY DESIGN: In a multicenter randomized controlled trial, spontaneously breathing VLBWIs weighing 800-1500 g were allocated to receive either therapy. In the CPAP/INSURE group, if respiratory distress syndrome (RDS) did not occur, CPAP was discontinued after 3-6 hours. If RDS developed and the fraction of inspired oxygen (FiO(2)) was >0.35, the INSURE protocol was indicated. Failure criteria included FiO(2) >0.60, severe apnea or respiratory acidosis, and receipt of more than 2 doses of surfactant. In the Oxygen/MV group, in the presence of RDS, supplemental oxygen without CPAP was given, and if FiO(2) was >0.35, surfactant and mechanical ventilation were provided. RESULTS: A total of 256 patients were randomized to either the CPAP/INSURE group (n = 131) or the Oxygen/MV group (n = 125). The need for mechanical ventilation was lower in the CPAP/INSURE group (29.8% vs 50.4%; P = .001), as was the use of surfactant (27.5% vs 46.4%; P = .002). There were no differences in death, pneumothorax, bronchopulmonary dysplasia, and other complications of prematurity between the 2 groups. CONCLUSION: CPAP and early selective INSURE reduced the need for mechanical ventilation and surfactant in VLBWIs without increasing morbidity and death. These results may be particularly relevant for resource-limited regions.

Is there a role for MRI in the preoperative assessment of patients with DCIS?

BACKGROUND: Breast magnetic resonance imaging (MRI) is used to identify residual and additional disease in patients with invasive carcinoma. The use of MRI in assessing extent of disease for ductal carcinoma in situ (DCIS) is less well defined. This study assessed the value of MRI in the preoperative evaluation of DCIS. MATERIALS AND METHODS: We identified 98 patients with DCIS in 2007. Of these, 63 underwent stereotactic biopsy, followed by MRI. There were 35 who underwent stereotactic biopsy alone. Concordance between MRI and histopathology was defined as the presence or absence of residual disease. RESULTS: There was no significant difference in mastectomy rates between the MRI and non-MRI group (20.3% vs 25.7%, P = .62). In patients undergoing breast-conserving surgery (BCS), there were fewer positive margins in the MRI versus the non-MRI group (21.2% vs 30.8%, P = .41). Of the 64 cases that underwent preoperative MRI, 43 (67.2%) were concordant. Also, 15 of 43 cases (34.8%) had MRI results that accurately predicted pathologic size. In 28 of 43 patients (65.2%), MRI overestimated disease in 20, by a mean of 1.97 cm. In patients with MRI tumor size >2 cm, MRI overestimated disease by a mean of 3.17 cm. Of the 64 cases, 21 (32.8%) were discordant. Also, 10 of 21 (47.6%) had a positive MRI and no residual disease on histopathology, and 11 of 21 (52.3%) had negative MRI and residual disease on pathology. CONCLUSIONS: MRI does not accurately predict extent of disease in patients with extensive DCIS. In patients with MRI tumor size < or = 2 cm, MRI may assist in surgical planning. MRI results in patients with DCIS should be interpreted with caution; decision for mastectomy should not be made on MRI findings alone.

Effect of gas and kerosene space heaters on indoor air quality: a study in homes of Santiago, Chile.

The impact of outdoor and indoor pollution sources on indoor air quality in Santiago, Chile was investigated. Toward this end, 16 homes were sampled in four sessions. Each session included an outdoor site and four homes using different unvented space heaters (electric or central heating, compressed natural gas, liquefied petroleum gas, and kerosene). Average outdoor fine particulate matter (PM2.5) concentrations were very high (55.9 microg x m(-3)), and a large fraction of these particles penetrated indoors. PM2.5 and several PM2.5 components (including sulfate, elemental carbon, organic carbon, metals, and polycyclic aromatic hydrocarbons) were elevated in homes using kerosene heaters. Nitrogen dioxide (NO2) and ultrafine particles (UFPs) were higher in homes with combustion heaters as compared with those with electric heaters or central heating. A regression model was used to assess the effect of heater use on continuous indoor PM2.5 concentrations when windows were closed. The model found an impact only for kerosene heaters (45.8 microg m(-3)).