Engagement in Meaningful Activity Mediates the Relationship Between Stressful Life Events and Functional Resilience.

Resilience during stressful life events is a priority for administering the most client-centered care as possible. Occupational therapy practitioners have the unique opportunity to support resilience through promoting meaningful participation. The current study aims to understand the associations between meaningful activity engagement, resilience, and stressful life events. We specifically focused on answering if meaningful participation mediates the relationship between stressful life events and resilience. 492 participants from a non-clinical convenience sample of Amazon's MTurk completed the study. Participants completed an online survey and reported their experiences of stressful life events, resilience, well-being, and meaningful participation. We used SPSS and PROCESS to analyze our data. Stressful event severity and resilience were inversely related. When accounting for the effect of meaningful participation, the relationship became non-significant, indicating evidence of mediation. Implications: Focusing on measuring meaningful participation may be worth studying in further research.

Engagement in Meaningful Activity Mediates the Relationship between Stressful Life Events and Functional ResilienceSupporting recovery both psychologically and physically after a stressful life event is an important aspect of providing client-centered care. By supporting patients' and clients' engagement in meaningful participation, therapists can promote resilient outcomes for all patients and clients. The current study explored the relationship between resilience and meaningful activity participation during stressful life events. The sample was comprised of a convenience sample of 492 participants who were recruited from the online crowdsourcing platform MTurk. The results of the study include that when the stressful life experience was more severe for an individual, they reported lower resilience scores. When meaningful activity participation was accounted for, the relationship between stressful life event severity and resilience became non-existent. The results of the study suggest the importance of using and measuring meaningful activity when supporting recovery after an stressful and adverse life event.

Impact of multidisciplinary team meetings on the management of patients with breast cancer in a large private healthcare facility.

AIMS: Multidisciplinary meetings (MDMs) play a crucial role in decision-making in breast cancer patient care. This study aimed to firstly assess the impact of breast cancer MDMs in decision-making for breast cancer patients and secondly to determine the concordance between MDM recommendations and implementation of clinical practice. METHODS: Patient cases to be presented at the weekly breast cancer MDMs were identified and prospectively enrolled. Management plans were predicted by the treating surgeon with the pre-MDM management plans then compared to MDM recommendations. Changes in decision-making were assessed in the following domains: further surgery, systemic therapy (endocrine, chemotherapy or targeted), radiotherapy, enrolment in a clinical trial, further investigations, and referral to other specialists or services. Patient records were subsequently reviewed at 3 months post-MDM to assess the rate of implementation of MDM recommendations and any reasons for discordance. RESULTS: Out of 50 cases, 66% (CI 53-79%; p < .005) experienced a change in management plan as a result of MDM discussion, with a total of 66 episodes of recorded change per decision-making domain affecting the following: further surgery (7.6%), endocrine therapy (4.5%), chemotherapy (19.7%), targeted therapy (4.5%), radiotherapy (18.2%), enrolment for a clinical trial (12.1%), additional investigations (22.7%), and further referrals (10.6%). MDM recommendations were implemented in 83.7% of cases. CONCLUSION: The breast cancer MDMs were found to substantially impact on the management plans for breast cancer patients, with 83.7% of MDM recommendations being implemented into clinical practice. This study reinforces the importance of MDMs in the management of these patients, as well as highlighting the need for further investigating and addressing the potential barriers to the implementation of MDM recommendations.

The interplay between pressure, flow, and resistance in neonatal pulmonary hypertension.

Pulmonary hypertension, conventionally defined by absolute pulmonary artery pressure, is the result of a range of diagnoses that can result in clinical problems in neonatal practice. Causes include persistent pulmonary hypertension of the newborn, congenital heart disease, and left heart dysfunction, as well as the normally high pulmonary artery resistance in neonates. Elucidating the cause of pulmonary hypertension is vital to guide appropriate management. A first principles approach based on hemodynamic calculations provides a framework for the diagnostic work up and subsequent therapy. Central to this is the equation 'pressure = flow x resistance' and knowledge of factors contributing to flow and resistance and their impact on pulmonary artery pressure. While formal, accurate, calculation of each element is usually not required or deliverable in small infants, clinical and echocardiographic parameters, combined with an understanding of the interplay between pressure, flow, and resistance, significantly improves the assessment and management of neonatal pulmonary hemodynamics.

Impact of Medical Operability and Total Metastatic Ablation on Outcomes After SABR for Oligometastases.

PURPOSE: Medical operability is prognostic for survival after SABR in primary malignancies. This study investigated the prognostic significance of medical operability and total versus subtotal ablation of all oligometastatic disease sites. METHODS AND MATERIALS: Consecutive patients with 1 to 5 sites of active extracranial oligometastases had medical operability status and presence of subtotal versus total metastatic ablation recorded prospectively in an institutional database. We retrospectively compared overall survival (OS) and progression-free survival (PFS) for medically operable or inoperable patients and patients undergoing total or subtotal metastatic ablation. Secondary endpoints were patterns of failure, high-grade treatment toxic effects (Common Terminology Criteria for Adverse Events version 4.0), and freedom from systemic therapy. The threshold dose per fraction considered ablative was 8 Gy. RESULTS: A total of 401 patients with 530 treated oligometastases were included, with a median follow-up of 3 years. Three hundred and two and 99 patients had metachronous and synchronous presentations of oligometastatic disease, respectively. Common histologies included prostate (24%), lung (18%), gastrointestinal (19%), and breast (11%). More than 90% of doses delivered were Biologically Effective Dose [BED10]≥60 Gy. Cumulative incidence at 5 years of local-only failure was 6%, local and distant 2%, and distant-only 58%. The 3- and 5-year OS [95% confidence intervals {CIs}] were 68% [62-73] and 54% [47-61], and PFS was 20% [15-25] and 14% [10-20]. The 3- and 5-year freedom from systemic therapy [95% CIs] were 40% [34-46] and 31% [24-37], respectively. Seventy-six patients were inoperable and 325 were operable. Operability status was not prognostic for OS (adjusted hazard ratio [HR], 1.0; 95% CI, 0.6-1.7; P = .9) or for PFS (adjusted HR, 1.1; 95% CI, 0.8-1.6; P = .5). Total metastatic ablation was prognostic for OS (adjusted HR, 0.8; 95% CI, 0.4-0.9; P = .032) and for PFS (adjusted HR, 0.6; 95% CI, 0.4-0.8; P = .003). CONCLUSIONS: Medical operability was not prognostic in patients with oligometastatic disease treated with SABR. Total metastatic ablation was associated with superior OS and PFS compared with subtotal metastatic ablation. Our data support ablation of all sites of oligometastases wherever feasible.

Combining Radiotherapy and Immunotherapy in Metastatic Breast Cancer: Current Status and Future Directions.

The role of radiotherapy and immunotherapy with immune checkpoint inhibitors (ICI) is of emerging interest in many solid tumours, including breast cancer. There is increasing evidence that the host's immune system plays an important role in influencing the response to treatment and prognosis in breast cancer. Several pre-clinical studies and clinical trials have reported on the 'abscopal effect-regression of distant untreated tumour sites, mediated by an immunological response following ionizing radiation to a targeted tumour site. Stereotactic Ablative Body Radiotherapy (SABR) is a non-invasive technique used to augment various immune responses with an ablative tumoricidal dose when compared to conventional radiotherapy. SABR is characterized by typically 1-5 precision radiotherapy treatments that simultaneously deliver a high dose, whilst sparing normal tissues. Following SABR, there is evidence of systemic immune activation in patients with increased PD1 expression on CD8+ and CD4+ T cells. Studies continue to focus on metastatic triple-negative disease, a highly immunogenic subtype of breast cancer with poor prognosis. In this review, we discuss the immunological effect of SABR, alone and in combination with immunotherapy, and the importance of dose and fractionation. We also propose future strategies for treating oligometastatic disease, where this approach may be most useful for producing durable responses.

SABR in oligometastatic breast cancer: Current status and future directions.

Oligometastatic breast cancer (OMBC) is a heterogeneous disease with intrinsic biological diversity. It is increasingly accepted in clinical practice that patients with OMBC could be treated with the expectation of long-term disease remission. Local ablative treatments, such as radiotherapy or surgery have a role in this setting. At present, patients that may benefit are characterised by low tumour burden, long disease-free interval and the capacity to completely ablate all sites of disease. In the future, biological or genomic classifiers may help predict which patients may benefit the most from local ablative treatments. This review provides an overview of the proposed classifications of oligometastatic disease and outlines the standard systemic treatment options of endocrine therapy, chemotherapy, and immunotherapy. The evidence for localized treatment with stereotactic ablative body radiotherapy (SABR) is presented. We discuss current active trials in oligometastatic cancer and discuss potential future directions for the use of SABR in the treatment of OMBC.

Cost-Minimization and Budget Impact Analysis of a Hexavalent Vaccine (Hexaxim®) in the Colombian Expanded Program on Immunization.

OBJECTIVES: To evaluate cost implications of a hexavalent vaccine (diphtheria, tetanus, and acellular pertussis [DTaP]-inactivated polio vaccine [IPV]-hepatitis B [HB]-Haemophilus influenzae type B [Hib] polysaccharide conjugated to T protein [PRP∼T]) as an alternative to DT-whole-cell pertussis (wP)-HB//Hib, DTwP, IPV, and oral polio vaccines in the Expanded Program on Immunization schedule in Colombia. METHODS: Primary vaccination (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV [2, 4, 6 months]) and booster (DTaP-IPV-HB-PRP∼T or DTwP + oral polio vaccine [18 months]) (scenario 1) and primary vaccination only (DTaP-IPV-HB-PRP∼T or DTwP-HB-Hib + IPV) (scenario 2) were evaluated. An estimated cost-minimization analysis was based on a micro costing technique for vaccination-associated activities. Adverse event (AE)-associated costs, out-of-pocket costs, and productivity losses for caregivers were included. A budget impact (12-month temporal horizon) was estimated according to the distribution of full-term and premature infants. A 5% annual discount rate was used. A 2-way univariate (tornado) analysis evaluated which variables had the greatest impact on the overall cost. RESULTS: DTaP-IPV-HB-PRP∼T resulted in a cost increase of 29.38% (scenario 1) and 22.19% (scenario 2) for full-term infants and a decrease of 0.99% (scenario 1) and 18.88% (scenario 2) for premature infants, probably because of the higher incidence of wP-related AEs and associated costs in premature infants. With a 100% replacement rate, the budget impact for full-term infants and full-term plus premature infants was 23.73% and 21.80% (scenario 1), respectively, and 13.02% and 11.14% (scenario 2), respectively, of the national immunization program budget. The variables with most impact were the hexavalent vaccine price and costs associated with the pentavalent safety profile. CONCLUSIONS: Incorporation of the hexavalent vaccine in the Expanded Program on Immunization schedule would lead to an increase in spending largely mitigated by reduced AE incidence and reduced logistic and social costs.

Consultant staffing in UK congenital cardiac services: a 10-year survey of leavers and joiners.

OBJECTIVES: To report the numbers of consultant congenital cardiac surgeons and cardiologists who have joined and left UK practice over the last 10 years and explore the reasons for leaving. METHODS: Retrospective observational questionnaire study completed between 11 June 2019 and 1 July 2020 by UK level 1 congenital cardiac centres of 10-year consultant staff movement and reasons suggested for leaving UK practice. RESULTS: At survey completion there were 218 (202 whole time equivalent (WTE)) consultant cardiologists and surgeons working within level 1 centres made up of 39 (38 WTE) surgeons, 137 (128.5 WTE) paediatric cardiologists, 42 (35.5 WTE) adult congenital heart disease (ACHD) cardiologists. 161 (74%) consultants joined in the last 10 years of whom 103 (64%) were UK trained. There were 91 leavers giving a staff turnover rate 42% (surgeons 56%, paediatric cardiologists 42%, ACHD cardiologists 29%). Of those, leaving 43% moved to work abroad (surgeons 55%, paediatric cardiologists 40%, ACHD cardiologists 67%). Among the 65 reported reasons for leaving 16 were financial, 9 for work life balance, 6 to working conditions within the National Health Service (NHS) and 12 related to the profession in the UK including six specifically highlighting the national review process. CONCLUSIONS: There has been a high turnover rate of consultant staff within UK congenital cardiac services over the last 10 years with almost half of those leaving moving to work overseas. Financial reasons and pressures relating to working in the NHS or the specialty in the UK were commonly reported themes for leaving. This has major implications for future planning and staff retention within this specialised service.

Stereotactic radiotherapy for oligoprogressive ER-positive breast cancer (AVATAR).

BACKGROUND: The enhanced knowledge of cancer biology has led to considerable advancement in systemic therapy for advanced breast cancer. Recently, studies showed that cyclin-dependent kinase (CDK) 4/6 inhibitor, when added to endocrine therapy, had improved the outcomes of patients with advanced ER-positive HER2-negative breast cancer. However, the disease often progresses following a period of treatment response. In a subset of patients, disease progression may occur at limited sites, i.e., oligoprogressive disease (OPD). In the past few years, stereotactic radiotherapy (SRT) has emerged as a safe and effective treatment for advanced cancer when delivered to limited metastatic sites. Hence, it is worth investigating the role of SRT in the setting of oligoprogressive breast cancer. METHOD: AVATAR is a multicentre phase II registry trial of SRT with endocrine therapy and CDK 4/6 inhibitor for the management of advanced ER-positive HER2-negative breast cancer. The study aims to enrol 32 patients with OPD limited to 5 lesions. The primary endpoint of the study is time to change systemic therapy measured from the commencement of SRT to change in systemic therapy. Secondary objectives include overall survival, progression free survival and treatment related toxicity. The exploratory objective is to describe the time to change in systemic therapy by the site (bone only vs. non-bone lesions) and number (1 vs. > 1) of OPD. DISCUSSION: This study aims to explore the effect of SRT in maximising the benefit of systemic therapy in patients with oligoprogressive ER-positive HER2-negative breast cancer. This approach might help reduce the burden of disease and improve the life quality in these patients. TRIAL REGISTRATION: ACTRN, ACTRN12620001212943 . Date of registration 16 November 2020- Retrospectively registered.

Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature.

Current first-line systemic treatment in most patients with metastatic hormone receptor-positive, HER-2 negative breast cancer is an aromatase inhibitor in combination with a cyclin dependant kinase (CDK) 4/6 inhibitor. Frequently, these patients require palliative radiotherapy (RT) for symptomatic disease management. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative RT, with conflicting case reports in the literature. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when palliative doses of RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. After review of pre-clinical and mechanistic data, we hypothesise that the effects of CDK4/6 inhibition on normal tissue and the tumour microenvironment may impede tissue recovery and exacerbate acute radiation and radiation recall toxicities. Further studies are required to clarify the potential toxicities of this combination. Clinicians should consider the potential risks when combining CDK 4/6 inhibitors with palliative RT and individualise patient management accordingly.

Safety, Efficacy, and Patterns of Failure After Single-Fraction Stereotactic Body Radiation Therapy (SBRT) for Oligometastases.

PURPOSE: Fewer attendances for radiation therapy results in increased efficiency and less foot traffic within a radiation therapy department. We investigated outcomes after single-fraction (SF) stereotactic body radiation therapy (SBRT) in patients with oligometastatic disease. METHODS AND MATERIALS: Between February 2010 and June 2019, patients who received SF SBRT to 1 to 5 sites of oligometastatic disease were included in this retrospective study. The primary objective was to describe patterns of first failure after SBRT. Secondary objectives included overall survival (OS), progression-free survival (PFS), high-grade treatment-related toxicity (Common Terminology Criteria for Adverse Events grade ≥3), and freedom from systemic therapy (FFST). RESULTS: In total, 371 patients with 494 extracranial oligometastases received SF SBRT ranging from 16 Gy to 28 Gy. The most common primary malignancies were prostate (n = 107), lung (n = 63), kidney (n = 52), gastrointestinal (n = 51), and breast cancers (n = 42). The median follow-up was 3.1 years. The 1-, 3-, and 5-year OS was 93%, 69%, and 55%, respectively; PFS was 48%, 19%, and 14%, respectively; and FFST was 70%, 43%, and 35%, respectively. Twelve patients (3%) developed grade 3 to 4 treatment-related toxicity, with no grade 5 toxicity. As the first site of failure, the cumulative incidence of local failure (irrespective of other failures) at 1, 3 and 5 years was 4%, 8%, and 8%, respectively; locoregional relapse at the primary was 10%, 18%, and 18%, respectively; and distant failure was 45%, 66%, and 70%, respectively. CONCLUSIONS: SF SBRT is safe and effective, and a significant proportion of patients remain FFST for several years after therapy. This approach could be considered in resource-constrained or bundled-payment environments. Locoregional failure of the primary site is the second most common pattern of failure, suggesting a role for optimization of primary control during metastasis-directed therapy.

Síndrome de Burnout y la psiconeuroendocrinoinmunología: consecuencias en el personal de salud durante la pandemia por Coronavirus / Burnout syndrome and psycho neuro endocrino immunology: consequences in health workers during the Coronavirus pandemic / Síndrome de burnout e psiconeuroendocrinoimmunologia: consequências em profissionais de saúde durante a pandemia de Coronavírus

Sr. Editor. Hasta la fecha se han documentado 7,439,220 de contagio por coronavirus (COVID-19) con una cifra de muertes de 961,400, de los cuales aproximadamente 7,000 hacen parte del personal de salud. En Colombia, las cifras por COVID-19 llegan a 758,398 con una mortalidad de 3,1%, lo que equivale a 24,039 muertes. Esto ha significado una gran carga mental para el personal de salud, conduciendo a un incremento en el número de suicidios por parte de este personal. Colombia no es ajena a la situación, tiene un reporte de 43,157 casos de los cuales 7,651 se dieron en médicos, 11,171 en auxiliares de enfermería, 4,611 en enfermeras profesionales. En cuanto a la mortalidad, hasta la fecha de revisión del 3 de febrero del 2021 había una cifra de 216 fallecidos de los cuales 71 eran médicos, 38 eran auxiliares de enfermería y trece enfermeras profesionales (1). DOI: https://doi.org/10.29375/01237047.3997

Until today, 7,439,220 infections have been documented by coronavirus (COVID-19) with a death toll of 961,400, of which approximately 7,000 make part of the health personnel. In Colombia, the figures for COVID-19 reaches 758,398 with a mortality of 3.1%, which is equivalent to 24,039 deaths. This has meant a great mental burden for health personnel, driving an increase in the number of suicides by this staff. Colombia is no stranger to the situation, it has a report from 43,157 cases of which 7,651 occurred in physicians, 11,171 in nursing assistants, 4,611 in nurses Professionals. Regarding mortality, to date revision of February 3, 2021 there was a figure of 216 deceased of which 71 were doctors, 38 were nursing assistants and thirteen professional nurses (1). DOI: https://doi.org/10.29375/01237047.3997

Até hoje, 7.439.220 infecções foram documentadas por coronavírus (COVID-19) com um número de mortes de 961.400, das quais aproximadamente 7.000 fazem parte do pessoal de saúde. Na Colômbia, os dados do COVID-19 chegam a 758.398 com mortalidade de 3,1%, o que equivale a 24.039 óbitos. Isso tem significado uma grande carga mental para o pessoal de saúde, levando a um aumento no número de suicídios dessa equipe. A Colômbia conhece bem a situação, tem um relatório de 43.157 casos, dos quais 7.651 ocorreram em médicos, 11.171 em auxiliares de enfermagem, 4.611 em profissionais de enfermagem. Em relação à mortalidade, até a data da revisão de 3 de fevereiro de 2021 havia 216 mortos, sendo 71 médicos, 38 auxiliares de enfermagem e treze profissionais de enfermagem (1). DOI: https://doi.org/10.29375/01237047.3997

Single-fraction stereotactic ablative body radiotherapy for sternal metastases in oligometastatic breast cancer: Technique and single institution experience.

INTRODUCTION: Due to size and close proximity to skin, the sternum is a complicated target for stereotactic ablative body radiotherapy (SABR). This is a retrospective case series of single-fraction SABR to sternal metastasis in patients with oligometastatic breast cancer. METHODS: Between June 2014 and June 2018, ten breast cancer patients received 20 Gy in 1 fraction to a solitary sternal metastasis. Eligible patients had Eastern Cooperative Oncology Group performance status of 0-2, oligometastatic disease (defined as 1-5 metastases) and a controlled primary site. Patients were treated with 3-dimensional conformal radiotherapy, each patient case comprising of> 6 coplanar beams and 2-6 non-coplanar beams. Local control, pain response and adverse events were retrospectively reviewed. RESULTS: The median planned target volumes were 84.75cc (range, 14.4-197.8cc). The median conformity index was 1.29 (range, 1.2-1.49). At a median follow-up of 32 months, nine patients achieved in-field control. Two patients had triple negative disease, one of them developed marginal recurrence, and the other had in-field recurrence. Seven patients had sternal pain prior to SABR, and within 3 months after SABR treatment, the pain improved (n = 3) or resolved (n = 2). Four patients developed acute grade 1 and 2 skin reactions, and two patients had late grade 1 skin reactions. There were no grade 3 or 4 toxicities. CONCLUSION: Our case series demonstrates safety of SABR with associated disease control and analgesic benefit in selected patients with oligometastatic breast cancer. The marginal recurrence observed in this cohort suggests wider margins could be beneficial to account for microscopic disease.

Stereotactic ablative body radiotherapy (SABR) for bone only oligometastatic breast cancer: A prospective clinical trial.

BACKGROUND: Stereotactic ablative body radiotherapy (SABR) is an emerging noninvasive approach for the treatment of oligometastases. Limited prospective evidence is available in breast cancer. OBJECTIVES: To determine the safety and feasibility of single fraction SABR for patients with bone only oligometastatic breast cancer. Secondary endpoints were local and distant progression-free survival (LPFS and DPFS), toxicity and response assessment. METHODS AND MATERIALS: In this single institution prospective trial we screened patients with computed tomography, bone scan, and sodium fluoride positron emission tomography. Eligible patients had one to three bone only oligometastases. All patients were treated at a dose of 20Gy in 1 fraction to each metastasis. Kaplan-Meier methods were used to determine local and distant progression free survival (LPFS and DPFS). Toxicity was graded using Common Terminology Criteria for Adverse Event version 4.0. RESULTS: 15 eligible patients were recruited to the study. Median follow-up time was 24 months. The treatment was feasible in 12 (80%) of patients with 3 (20%) of patients having treatment delayed by more than 3 days. 10 (67%) of patients experienced grade 1 treatment related toxicity, 4 (27%) experienced grade 2 toxicity and no patients experienced grade 3 or 4 treatment related toxicity. The two-year LPFS was 100%, DPFS was 67%. CONCLUSION: We observed that SABR is feasible, well tolerated and effective in this cohort with two thirds of patients disease-free at two years. In selected patients with bone-only oligometastatic disease, SABR could be considered a treatment option. Randomised trials are required to assess the impact of SABR on overall survival when compared to the standard of care.

Dose reduction to organs at risk with deep-inspiration breath-hold during right breast radiotherapy: a treatment planning study.

BACKGROUND: The addition of regional nodal radiation (RNI) to whole breast irradiation for high risk breast cancer improves metastases free survival and new data suggests it contributes additional benefit to overall survival. Deep inspiration breath hold (DIBH) has been shown to reduce cardiac and pulmonary dose in the context of left-sided disease treated with or without RNI, yet few studies have investigated its utility for right-breast cancer. This study investigates the potential advantages of DIBH in local and locoregional radiotherapy for right-sided breast cancer. METHODS: Free-breathing (FB) and DIBH computed tomography datasets were obtained from twenty patients who previously underwent radiotherapy for left-sided breast cancer. Ten patients were retrospectively planned for whole right breast only irradiation and ten patients were planned for irradiation to the whole breast plus ipsilateral supra-clavicular (SC) nodes, with and without irradiation of the ipsilateral internal mammary nodes (IMN). Dose-volume metrics for the clinical target volume, lungs, heart, left anterior descending artery, right coronary artery (RCA) and liver were recorded. Differences between FB and DIBH plans were analysed using Wilcoxon signed-rank tests, with P < 0.05 considered statistically significant. RESULTS: DIBH increased the average total lung volume compared to FB in both breast only and breast plus RNI cohorts (P = 0.001). For the breast only group, there was no significant improvement in any ipsilateral lung dose-volume metric between FB and DIBH. However, for the breast plus RNI group, there was an improvement in ipsilateral lung mean dose (18.9 ± 3.2 Gy to 15.9 ± 2.3 Gy, P = 0.002) and V20Gy (45.3 ± 13.3% to 32.9 ± 9.4%, P = 0.002). In addition, DIBH significantly reduced the maximum dose to the RCA for RNI (11.6 ± 7.2 Gy to 5.6 ± 2.9 Gy, P = 0.03). Significant reductions in the liver V20Gy and maximum dose were observed in all cohorts during DIBH compared to FB. CONCLUSIONS: DIBH is a promising approach for right-breast radiotherapy with considerable sparing of normal tissue, particularly when the ipsilateral IMNs are also irradiated.

Estudio climatológico de los vientos para la ciudad de Bogotá en el periodo 2010 - 2016 / Climatological study of the winds for the city of Bogotá in the period 2010-2016 / Estudo climatológico dos ventos para a cidade de Bogotá no período de 2010 a 2016

Resumen En Colombia, hay una carencia en los estudios climatológicos del viento, ya que, los que existen actualmente no aplican técnicas estadísticas ni periodos representativos adecuados. Por consiguiente, el presente estudio analiza el comportamiento climatológico del viento en la ciudad de Bogotá, para el periodo 2010 a 2016, buscando describir estadística, espacial y vectorialmente esta variable climatológica. Para empezar se realizó un análisis estadístico del conjunto de datos, de la velocidad del viento, mediante el software Windographer©, utilizando las técnicas exploratorias para la distribución Weibull, describiendo así los parámetros estadísticos de las estaciones en las principales zonas de la ciudad. Del mismo modo, se elaboraron las rosas de los vientos por estación, con el software WRPLOT™; y para finalizar se realizó un mapa vectorial mediante el método de interpolación Co-Kriging utilizando el sistema de información geográfica ArcGis®. Observando que el régimen de circulación atmosférico en Bogotá está estrechamente relacionado con la presencia de los cerros orientales y con la predominancia de los vientos alisios; así mismo, se encontró que la mayor velocidad del viento se presenta al suroeste, y las magnitudes más débiles, al norte y en cercanía a los cerros orientales.

Abstract In Colombia, there is a lack in wind weather studies, since those that currently exist do not apply statistical techniques or adequate representative periods. Therefore, the present study analyzes the wind weather behavior in the city of Bogotá, for the period 2010 to 2016, seeking to describe this weather variable statistically spatially and vectorially. To begin with, a statistical analysis of the data set, of the wind speed, was performed using the Windographer© software, using the exploratory techniques for the Weibull distribution, thus describing the statistical parameters of the stations in the main areas of the city. Similarly wind roses were made per season, using the WRPLOT ™ software; and, finally, a vector map was made using the Co-Kriging interpolation method, using the ArcGis® geographic information system. Noting that the atmospheric circulation regime in Bogotá is closely related to the presence of the eastern hills and the predominance of trade winds; Likewise, it was found that the highest wind speed is presented to the southwest, and the weakest magnitudes, to the north and in proximity to the eastern hills.

Resumo Na Colômbia, há falta de estudos sobre o clima do vento, uma vez que os existentes atualmente não aplicam técnicas estatísticas ou períodos representativos adequados. Portanto, o presente estudo analisa o comportamento do clima eólico na cidade de Bogotá, no período de 2010 a 2016, buscando descrever esta variável climática de forma estatística, espacial e vetorial. Para começar foi realizada uma análise estatística do conjunto de dados, da velocidade do vento, utilizando o software Windographer©, utilizando as técnicas exploratórias para a distribuição de Weibull, descrevendo assim os parâmetros estatísticos das estacoes nas principais áreas da cidade. Da mesma forma, foram feitas rosas de vento por temporada, usando o software WRPLOT ™; e, finalmente, foi feito um mapa vetorial usando o método de interpolação Co-Kriging, usando o sistema de informação geográfica ArcGis®. Observando que o regime de circulação atmosférica em Bogotá está intimamente relacionado com a presença dos montes orientais e predominância de ventos alísios; da mesma forma, verificou-se que a maior velocidade do vento é apresentada na região sudeste, e as magnitudes mais fracas, ao norte e nas proximidades das colinas orientais.

Neoadjuvant neratinib promotes ferroptosis and inhibits brain metastasis in a novel syngeneic model of spontaneous HER2+ve breast cancer metastasis.

BACKGROUND: Human epidermal growth factor receptor-2 (HER2)-targeted therapies prolong survival in HER2-positive breast cancer patients. Benefit stems primarily from improved control of systemic disease, but up to 50% of patients progress to incurable brain metastases due to acquired resistance and/or limited permeability of inhibitors across the blood-brain barrier. Neratinib, a potent irreversible pan-tyrosine kinase inhibitor, prolongs disease-free survival in the extended adjuvant setting, and several trials evaluating its efficacy alone or combination with other inhibitors in early and advanced HER2-positive breast cancer patients are ongoing. However, its efficacy as a first-line therapy against HER2-positive breast cancer brain metastasis has not been fully explored, in part due to the lack of relevant pre-clinical models that faithfully recapitulate this disease. Here, we describe the development and characterisation of a novel syngeneic model of spontaneous HER2-positive breast cancer brain metastasis (TBCP-1) and its use to evaluate the efficacy and mechanism of action of neratinib. METHODS: TBCP-1 cells were derived from a spontaneous BALB/C mouse mammary tumour and characterised for hormone receptors and HER2 expression by flow cytometry, immunoblotting and immunohistochemistry. Neratinib was evaluated in vitro and in vivo in the metastatic and neoadjuvant setting. Its mechanism of action was examined by transcriptomic profiling, function inhibition assays and immunoblotting. RESULTS: TBCP-1 cells naturally express high levels of HER2 but lack expression of hormone receptors. TBCP-1 tumours maintain a HER2-positive phenotype in vivo and give rise to a high incidence of spontaneous and experimental metastases in the brain and other organs. Cell proliferation/viability in vitro is inhibited by neratinib and by other HER2 inhibitors, but not by anti-oestrogens, indicating phenotypic and functional similarities to human HER2-positive breast cancer. Mechanistically, neratinib promotes a non-apoptotic form of cell death termed ferroptosis. Importantly, metastasis assays demonstrate that neratinib potently inhibits tumour growth and metastasis, including to the brain, and prolongs survival, particularly when used as a neoadjuvant therapy. CONCLUSIONS: The TBCP-1 model recapitulates the spontaneous spread of HER2-positive breast cancer to the brain seen in patients and provides a unique tool to identify novel therapeutics and biomarkers. Neratinib-induced ferroptosis provides new opportunities for therapeutic intervention. Further evaluation of neratinib neoadjuvant therapy is warranted.

Outcome following heart transplant assessment in adults with congenital heart disease.

OBJECTIVES: Adults with congenital heart disease (ACHD) are a growing group with end-stage heart failure. We aim to describe the outcomes of ACHD patients undergoing assessment for orthotopic heart transplant (OHT). METHODS: Case notes of consecutive ACHD patients (>16 years) assessed for OHT between 2000 and 2016 at our centre were reviewed. Decision and outcome were reported as of 2017. Data were analysed in three groups: systemic left ventricle (LV), systemic right ventricle (RV) and single ventricle (SV). RESULTS: 196 patients were assessed (31.8 years, 27% LV, 29% RV, 44% SV). 89 (45%) patients were listed for OHT and 67 (34%) were transplanted. 41 (21%) were unsuitable or too high risk and 36 (18%) were too well for listing. Conventional surgery was undertaken in 13 (7%) and ventricular assist device in 17 (9%) with 7 (4%) bridged to candidacy. Survival from assessment was 84.2% at 1 year and 69.7% at 5 years, with no difference between groups. Patients who were considered unsuitable for OHT (HR 11.199, p<0.001) and listed (HR 3.792, p=0.030) were more likely to die than those who were considered too well. Assessments increased over the study period. CONCLUSIONS: The number of ACHD patients assessed for OHT is increasing. A third are transplanted with a small number receiving conventional surgery. Those who are unsuitable have a poor prognosis.

Porencefalia, reporte de caso / Porencephaly, report of a case

La porencefalia como lesión cerebral es una entidad que por el gran compromiso encefálico genera déficits motores y conductuales afectando el normal desarrollo de niños, siendo este el grupo poblacional principalmente afectado; quienes desde muy temprana edad presentan manifestaciones clínicas, sin embargo en algunos casos excepcionales tienden a cursan asintomáticos o con mínimas secuelas motoras que pueden retrasar su diagnóstico; campo en que las técnicas de imagen llegan a ser fundamentales. Se presenta aquí el primer caso de porencefalia reportado en Boyacá a la edad adulta sin antecedentes que sugieran su diagnóstico o algún manejo instaurado a la misma, la cual termina complicándose dejando varias secuelas..(AU)

Porencephaly as a brain injury is an entity that due to the great encephalic engagement generates motor deficits and behavioral affections on the normal development of children, being this the population group mainly affected, who from a very early age present clinical manifestations, however some exceptional cases are asymptomatic or has minimal motor sequelae that may delay their diagnosis; a sphere in which imaging techniques become fundamental. Here we present the first case of porencephaly reported in Boyacá to adulthood without a history suggesting its diagnosis or some management established to it, which ends up complicating leaving several sequelae..(AU)

The impact of imaging modality (CT vs MRI) and patient position (supine vs prone) on tangential whole breast radiation therapy planning.

PURPOSE: The purpose of this study was to evaluate the impact of magnetic resonance imaging (MRI) versus computed tomography (CT)-derived planning target volumes (PTVs), in both supine and prone positions, for whole breast (WB) radiation therapy. METHODS AND MATERIALS: Four WB radiation therapy plans were generated for 28 patients in which PTVs were generated based on CT or MRI data alone in both supine and prone positions. A 6-MV tangential intensity modulated radiation therapy technique was used, with plans designated as ideal, acceptable, or noncompliant. Dose metrics for PTVs and organs at risk were compared to analyze any differences based on imaging modality (CT vs MRI) or patient position (supine vs prone). RESULTS: With respect to imaging modality 2/11 whole breast planning target volume (WB_PTV) dose metrics (percentage of PTV receiving 90% and 110% of prescribed dose) displayed statistically significant differences; however, these differences did not alter the average plan compliance rank. With respect to patient positioning, the odds of having an ideal plan versus a noncompliant plan were higher for the supine position compared with the prone position (P = .026). The minimum distance between the seroma cavity planning target volume (SC_PTV) and the chest wall was increased with prone positioning (P < .001, supine and prone values 1.1 mm and 8.7 mm, respectively). Heart volume was greater in the supine position (P = .005). Heart doses were lower in the supine position than prone (P < .01, mean doses 3.4 ± 1.55 Gy vs 4.4 ± 1.13 Gy for supine vs prone, respectively). Mean lung doses met ideal dose constraints in both positions, but were best spared in the prone position. The contralateral breast maximum dose to 1cc (D1cc) showed significantly lower doses in the supine position (P < .001, 4.64 Gy vs 9.51 Gy). CONCLUSIONS: Planning with PTVs generated from MRI data showed no clinically significant differences from planning with PTVs generated from CT with respect to PTV and doses to organs at risk. Prone positioning within this study reduced mean lung dose and whole heart volumes but increased mean heart and contralateral breast doses compared with supine.