Touching tumour-infiltrating lymphocytes in low-risk ductal carcinoma in situ (DCIS) correlate with upgrading to high-grade DCIS.

AIMS: To examine our hypothesis that a higher number of touching tumour-infiltrating lymphocytes (TILs) in low-risk ductal carcinoma in situ (DCIS) detected in a setting such as an active surveillance clinical trial correlates with upgrading to high-grade DCIS (HG-DCIS) in the subsequent excisional biopsy. METHODS AND RESULTS: The clinical inclusion criteria of the Comparison of Operative versus Monitoring and Endocrine Therapy (COMET) trial were applied to women who were mammographically screened between 2007 and 2017. In the core needle biopsy, touching TILs were assessed by counting the number of TILs touching the ductal basement membrane or away from it by one lymphocyte thickness. The highest number of TILs around a single involved duct and the average number among involved ducts were recorded. DCIS was graded as low or intermediate. Twenty-six of 129 (20.2%) cases had upgrading [14 (10.9%) to pure HG-DCIS, and 12 (9.3%) to invasive carcinoma, two of them with concurrent HG-DCIS]. An increased average number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 11 of 16 (68.8%) cases, and a decreased average number of touching TILs and low-grade DCIS correlated with no upgrading in 89 of 113 (78.8%) cases [accuracy of 0.775; area under the curve (AUC) of 0.746]. An increased highest number of touching TILs and intermediate-grade DCIS correlated with upgrading to HG-DCIS in 12 of 16 (75%) cases, and a decreased highest number of touching TILs and low-grade DCIS correlated with no upgrading in 82 of 113 (72.6%) cases (accuracy of 0.7287; AUC of 0.734). A highest number of touching TILs of ≥10 correlated with upgrading to invasive carcinoma and/or HG-DCIS (P = 0.018). CONCLUSIONS: Intermediate-grade and touching TILs may be good variables to examine in the COMET trial and to correlate with the risk of upgrading.

Surveillance of probably benign (BI-RADS 3) lesions in mammography: what is the right follow-up protocol?

BI-RADS-3 is a category in mammography for probably benign lesions and for which periodic follow-up with repeat imaging is recommended. At our institution repeated mammograms are performed at 6, 12, 18, and 24 months. The purpose of this study was to assess the significance of 18-month mammogram for evaluation of BI-RADS-3 lesions. Following IRB approval, electronic medical records and picture archiving and communications system were used to review 121,862 consecutive mammograms between February, 2002-May, 2009. A total of 8,400 patients with BI-RADS-3 mammograms were identified. Of these, 7,632 patients were followed until completion of 24 month mammogram or biopsy following an upgrade in their BI-RADS status. Over the follow-up, 197 patients received an upgrade in their BI-RADS status of which 179 were biopsied. Histopathologic results were reviewed. The majority of the BI-RADS-3 lesions were upgraded at 6-month mammogram (n = 150, 76.1%) followed by 32 (16.2%), 11 (5.6%), and 4 (2.0%) at 12, 18, and 24 month mammograms respectively. Thirty-four of 179 upgraded and biopsied lesions were found to be malignant. From these 27 (79.4%), 3 (8.8%), 3 (8.8%), and 1 (2.9%) lesions were identified at 6, 12, 18, and 24 month mammograms respectively. At the 18-month mammogram 3/7,632 lesions (0.04%) were found to be malignant. The vast majority of malignant lesions (88.2%) were detected within the first 12-months of follow-up. Only three of 179 biopsies (1.7%) were malignant at 18-month follow-up. Based on those results a 6-, 12-, and 24-month follow-up protocol for BI-RADS-3 lesions is sufficient.

NICU parent-to-parent partnerships: a comprehensive approach.

Parents of newborns in the neonatal intensive care unit (NICU) find themselves in a world of unknown medical terminology, advanced technology, and the realization that their dream of a healthy baby has been shattered. The unique partnership with trained parent-to-parent volunteers, who have had previous NICU experiences, enhances professional support and helps new NICU parents adjust to these unexpected challenges. This practice-based article describes the Helen DeVos Children's Hospital NICU Parent-to-Parent Partnership's (PPP) 40-year commitment to the parent-to-parent philosophy and its comprehensive approach to delivering trained volunteer PPP services to NICU families. A historical review of the literature, including this hospital's original research, current programming, recruiting, training, supervision, and survey feedback, is outlined.

Imaging findings of "anesthesia mumps" (acute postoperative sialadenitis) after general anesthesia.

We present a rare case of acute postoperative sialadenitis or "anesthesia mumps" necessitating emergent intubation in a 16-year-old girl after biopsy of a brainstem mass under general anesthesia. Postoperative computed tomography of the brain demonstrated extensive right-sided facial swelling, parotid gland enlargement, and pharyngeal edema extending to the parapharyngeal space, soft palate, and uvula with significant narrowing of the airway. To our knowledge, this entity has not been previously described in the radiologic literature.

Significance of Removing Comedonecrosis as an Exclusion Criterion in Mammary Low-Risk Ductal Carcinoma In Situ Managed in an Active Surveillance Clinical Trial.

OBJECTIVES: This study aims to investigate the consequences of comedonecrosis omission as an exclusion criterion of the Comparison of Operative vs Monitoring and Endocrine Therapy (COMET) trial. METHODS: The clinical inclusion criteria of the COMET trial were applied on women who were mammographically screened between 2007 and 2017 and had a diagnosis of low- or intermediate-grade ductal carcinoma in situ (DCIS). The percentage of ductal diameter occupied by necrosis was calculated. RESULTS: Twenty-six of 129 (20.2%) cases were upgraded. Larger calcification span correlated with upgrade (P = .02), with the best cutoff of 1.1 cm, and negative predictive value of 86%. When solely analyzing cases with no comedonecrosis (n = 76), none of the variables correlated with upgrade. Comedonecrosis was significantly correlated with upgrade to invasive carcinoma (P = .041), with the best cutoff of 53% of ductal diameter occupied by necrosis. CONCLUSIONS: Results indicate that comedonecrosis and span of mammographic calcifications could be risk factors in women managed with active surveillance.

Options to Determine Pathological Response of Axillary Lymph Node Metastasis after Neoadjuvant Chemotherapy in Advanced Breast Cancer.

Increasing use of neoadjuvant therapy in large tumors or node positive disease in breast cancer patients or hormone negative and HER 2 overexpressing cancers often gives rise to complete clinical response, with resolution of disease in the breast and axilla. These results have raised important questions to deescalate loco-regional surgical treatment options with minimum recurrence risk and treatment related morbidity. Although there is excellent prognosis following clinical response, the primary goal of surgery still remains to confirm complete pathological response in the biopsied node that was previously positive and now clinically/radiologically negative (ycN0). Biopsied lymph nodes are often marked with a clip to allow future identification at the time of definitive surgery. The goal of lymph node surgery in oncology is that it should be accurate, hence the significance of localizing the biopsied node. This article aims to review the different options to localize the deemed positive node at the time of definitive surgery, in order to help determine pathological response after neoadjuvant therapy.

Support for siblings of NICU patients: an interdisciplinary approach.

Siblings of hospitalized newborns in neonatal intensive care units (NICU) experience unique thoughts and feelings in response to this situational crisis. Providing an opportunity for siblings and their parents to address both of their concerns can improve sibling adjustment to the NICU, and is also consistent with a family-centered care philosophy. This article traces the development and evolution of sibling policy and program changes at Helen DeVos Children's Hospital (HDVCH) NICU, and describes the current comprehensive model for inclusion of siblings. Particular emphasis will be given to the cornerstone program "Celebrating Siblings Pizza Party." Infection control considerations and the importance of an interdisciplinary team approach to enhance an array of sibling services are also highlighted.

Atypical Ductal Hyperplasia and Those Bordering on Ductal Carcinoma In Situ Should Be Included in the Active Surveillance Clinical Trials.

OBJECTIVES: Women with atypical ductal hyperplasia (ADH), unlike those with ductal carcinoma in situ (DCIS), are denied eligibility for active surveillance clinical trials. METHODS: We applied the inclusion criteria of the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial to the cases of women (n = 165) at the Roswell Park Cancer Institute who had a diagnosis of ADH, ADH bordering on DCIS, or low- to intermediate-grade DCIS on core biopsy taken during screening mammography. Upgrade of lesions to high risk was based on invasive carcinoma, high-grade DCIS, or DCIS with comedo necrosis. RESULTS: In total, nine (5.5%) lesions were upgraded: two (1.7%) reported ADH, one (5.9%) reported ADH bordering on DCIS, and six (19.4%) reported DCIS (P = .002); and two (1.6%) reclassified ADH vs seven (17.1%) reclassified DCIS (P < .001). In multivariate analysis, only increased number of foci had the potential to predict high risk (odds ratio: 1.39; P = .06). CONCLUSIONS: We conclude that ADH and ADH bordering on DCIS have lower upgrade rates than DCIS. We recommend opening an active surveillance clinical trial for women with these diagnoses.

Risk of narcolepsy associated with inactivated adjuvanted (AS03) A/H1N1 (2009) pandemic influenza vaccine in Quebec.

CONTEXT: An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe. OBJECTIVE: To assess narcolepsy risk following administration of a similar vaccine in Quebec. DESIGN: Retrospective population-based study. SETTING: Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre. POPULATION: Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry. MAIN OUTCOME MEASURES: Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1st, 2009, and December 31st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method. RESULTS: A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009-2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50-11.12). RR was 2.07 (0.70-6.17) in the SCCS, and 1.48 (0.37-7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases. CONCLUSIONS: Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.

Dobutamine alters carnitine metabolism in the neonatal piglet heart.

UNLABELLED: The use of inotropic agents to support the neonatal heart after sepsis or hypoxia increases cardiac energy demand. Carnitine plays a vital role in energy, fuel metabolism. To test the hypothesis that inotropic agents affect carnitine metabolism, hearts from sow-fed piglets were isolated and perfused with an oxygenated buffer containing glucose and palmitate. Increasing dosages of dobutamine (DOB 2.5-15 microg/Kg body wt per min, 0.007-0.044 micromol/kg per min) or saline vehicle (SAL) were administered. Heart rate (HR), left ventricular systolic (LVSP) and end diastolic pressures (LVEDP) were measured. Left ventricular developed pressure (LVDP = LVSP-LVEDP) and pressure-rate product (LVDP x HR) were calculated. Coronary effluent was collected to measure flow and metabolites. Heart tissue samples were collected for metabolite analysis. RESULTS: DOB increased HR, LVEDP and the pressure-rate product [LVDP x HR]. Mean lactate production increased in DOB, but not in SAL control hearts, and was correlated with heart acylcarnitine, but not with coronary flow. Tissue acylcarnitine levels were higher in the DOB than in the SAL group. Plasma total carnitine was correlated with [LVDP x HR] and LVDP, but not with HR. The findings demonstrate that DOB alters myocardial carnitine metabolism and suggest that carnitine status may affect cardiac response to inotropic agents.

Preparing Europe for a new renaissance: how science can help restore sustainable prosperity

El 6 de octubre de 2009, la Oficina del Espacio Europeo de Investigación (ERAB, en sus siglas en inglés) presentó su primer informe anual "Preparing Europe for a New Renaissance - A Strategic View of the European Researh Area". Como un documento global, el informe señala, a grandes rasgos, las directrices en las que se ha de enmarcar el Espacio Europeo de Investigación (ERA, en sus siglas en inglés) de aquí a 2030 - en aras de la Unión Europea y del mundo en general. Con este propósito, los días 6 y 7 de mayo de 2010, se celebró en la ciudad española de Sevilla, la Conferencia ERAB bajo el lema expuesto: "Preparing Europe for a new Renaissance". El objetivo de la Conferencia ERAB era discutir ampliamente con las partes interesadas públicas y privadas la aplicación de la visión estratégica sobre el Espacio Europeo de Investigación. Mención especial merece la Comisaria Máire Geoghegan Quinn, quien, quien planteó un desafío a la Conferencia ERAB en su discurso. Así, pidió a la conferencia diez propuestas concretas sobre cómo la Investigación, la Innovación, y la Ciencia pueden contribuir a abordar los grandes desafíos de la sociedad, para dar paso una economía inteligente y verde y a una sociedad de la Europa poscrisis. ERAB aceptó el desafío. Basándose en la respuesta de los delegados de la conferencia y los debates internos, ERAB identificó 10 recomendaciones clave. Reproducimos a continuación el discurso pronunciado por la Comisaria Europea de Investigación, Innovación y Ciencia, Máire Geoghegan Quinn en la ERAB Conference (AU)

On 6 October 2009, ERAB (European Research Area Board) presented its first anual report "Preparing Europe for a New Renaissance - A Strategic View of the European Research Area". As a vision paper it paints a picture, in broad strokes, of where the European Research Area (ERA) needs to go by 2030 - for the sake of the European Union, and of the world at large. For this purpose, the ERAB Conference entitled "Preparing Europe for a new Renaissance" was held on May 6 -7, 2010, in Seville, Spain. The aim of the ERAB Conference was to discuss widely with public and private stakeholders the implementation of the Strategic view on Europen a Research Area. The Commissioner Máire Geoghegan Quinn deserves a special mention since set a challenge to the ERAB Conference in her speech. Thus, she asked the Conference to provide her with ten concrete proposals on how Research, Innovation and Science can contribute to addressing society´s Grand Challenges, to prepare Europe´s post crisis smart, green economy and society. The ERAB welcomed the challenge. Based on the feedback from the conference delegates and own discussions the ERAB came up with 10 key recommendations. Below we reproduce a speech by the European Commissioner for Research, Innovation and Science, Máire Geoghegan Quinn given at the ERAB Conference (AU)