Patient-reported outcomes of immediate implant-based breast reconstruction with and without biological or synthetic mesh.

BACKGROUND: Biological and synthetic meshes may improve the outcomes of immediate implant-based breast reconstruction (IBBR) by facilitating single-stage procedures and improving cosmesis. Supporting evidence is, however, limited. The aim of this study was to explore the impact of biological and synthetic mesh on patient-reported outcomes (PROs) of IBBR 18 months after surgery. METHODS: Consecutive women undergoing immediate IBBR between February 2014 and June 2016 were recruited to the study. Demographic, operative, oncological and 3-month complication data were collected, and patients received validated BREAST-Q questionnaires at 18 months. The impact of different IBBR techniques on PROs were explored using mixed-effects regression models adjusted for clinically relevant confounders, and including a random effect to account for clustering by centre. RESULTS: A total of 1470 participants consented to receive the questionnaire and 891 completed it. Of these, 67 women underwent two-stage submuscular reconstructions. Some 764 patients had a submuscular reconstruction with biological mesh (495 women), synthetic mesh (95) or dermal sling (174). Fourteen patients had a prepectoral reconstruction. Compared with two-stage submuscular reconstructions, no significant differences in PROs were seen in biological or synthetic mesh-assisted or dermal sling procedures. However, patients undergoing prepectoral IBBR reported better satisfaction with breasts (adjusted mean difference +6.63, 95 per cent c.i. 1.65 to11.61; P = 0.009). PROs were similar to those in the National Mastectomy and Breast Reconstruction Audit 2008-2009 cohort, which included two-stage submuscular procedures only. CONCLUSION: This study found no difference in PROs of subpectoral IBBR with or without biological or synthetic mesh, but provides early data to suggest improved satisfaction with breasts following prepectoral reconstruction. Robust evaluation is required before this approach can be adopted as standard practice.

Morbidity and Complications of Diabetes Mellitus in Children and Adolescents in Ghana: Protocol for a Longitudinal Study.

BACKGROUND: Diabetes is associated with premature morbidity and mortality from its many complications. There are limited data on the chronic complications of diabetes in children and adolescents in sub-Saharan Africa. OBJECTIVE: The study aims to determine the (1) burden and related factors of chronic systemic complications of diabetes, including diabetic and nondiabetic ocular conditions in children and adolescents, and (2) quality of life (QoL) of participants compared to healthy controls. This manuscript describes the study methodology. METHODS: Demographic information, medical history, anthropometric measurements, and laboratory characteristics were collected, and the participants were screened for microvascular and macrovascular complications as well as nondiabetic ocular disease. QoL questionnaires were administered to participants, their caregivers, and controls. Participants were followed up annually up to 3 years to determine the natural history of and trends in these conditions. SPSS Version 25.0 will be used for data analysis. Continuous and categorical data will be presented as mean (SD) and as percentages (%), respectively. t tests and analysis of variance will be used to compare means, and chi-square tests will be used to compare categorical data. Correlation, regression, and logistic regression analyses will be employed to establish linear associations and causal associations as appropriate. Relative risk and odds ratios will be used to estimate risk. QoL outcomes in Ghanaian children and adolescents with diabetes mellitus compared with caregivers and healthy controls will be assessed using the Pediatric Quality of Life inventory. Significance will be set at α=.05. RESULTS: Institutional approval from the Ethical and Protocol Review Committee of the University of Ghana Medical School was received on August 22, 2014 (Protocol Identification Number: MS-Et/M.12-P4.5/2013-2014). Funding for the project was received from the University of Ghana Research Fund (#UGRF/9/LMG-013/2015-2016) in March 2016. Patient recruitment, clinical examination, and data collection commenced in August 2016 and was completed in September 2019. A total of 58 children and adolescents with diabetes mellitus have been recruited. Blood samples were stored at -80 °C for analysis, which was completed at the end of July 2020. Data analysis is ongoing and will be completed by the end of December 2020. Investigators plan to submit the results for publication by the end of February 2021. CONCLUSIONS: The prevalence, natural history, trends in diabetic complications and nondiabetic ocular disease, and QoL will be provided. Our data may inform policies and interventions to improve care given to children and adolescents with diabetes. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21440.

Experiences of implant loss after immediate implant-based breast reconstruction: qualitative study.

BACKGROUND: Immediate implant-based breast reconstruction (IBBR) is the most commonly performed reconstructive procedure in the UK, but almost one in ten women experience implant loss and reconstructive failure after this technique. Little is known about how implant loss impacts on patients' quality of life. The first phase of the Loss of implant Breast Reconstruction (LiBRA) study aimed to use qualitative methods to explore women's experiences of implant loss and develop recommendations to improve care. METHODS: Semistructured interviews were conducted with a purposive sample of women who experienced implant loss after immediate IBBR, performed for malignancy or risk reduction across six centres. Interviews explored decision-making regarding IBBR, and experiences of implant loss and support received. Thematic analysis was used to explore the qualitative interview data. Sampling, data collection and analysis were undertaken concurrently and iteratively until data saturation was achieved. RESULTS: Twenty-four women were interviewed; 19 had surgery for malignancy and five for risk reduction. The median time between implant loss and interview was 42 (range 22-74) months. Ten women had undergone secondary reconstruction, two were awaiting surgery, and 12 had declined further reconstruction. Three key themes were identified: the need for accurate information about the risks and benefits of IBBR; the need for more information about 'early-warning' signs of postoperative problems, to empower women to seek help; and better support following implant loss. CONCLUSION: Implant loss is a devastating event for many women. Better preoperative information and support, along with holistic patient-centred care when complications occur, may significantly improve the experience and outcome of care.

ANTECEDENTES: La reconstrucción mamaria inmediata con prótesis (implant-based breast reconstruction, IBBR) es el procedimiento reconstructivo más utilizado en el Reino Unido, pero casi una de cada diez mujeres presentará pérdida de la prótesis y fallo del procedimiento reconstructivo tras esta técnica. Se sabe poco de cómo la pérdida de la prótesis afecta la calidad de vida de las pacientes. La primera fase del estudio LiBRA tuvo como objetivo explorar la percepción de las mujeres ante la pérdida de la prótesis, utilizando métodos cualitativos, y proponer una serie de medidas para mejorar la atención sanitaria de estas pacientes. MÉTODOS: Se realizaron entrevistas semiestructuradas en una muestra de mujeres que padecieron la pérdida de la prótesis tras una IBBR inmediata, realizada por neoplasia o como procedimiento de reducción de riesgo, en seis centros. Las entrevistas analizaron la toma de decisiones con respecto a la IBBR inmediata, así como la percepción ante la pérdida del implante y el soporte recibido. Se utilizó un análisis por temas para examinar los datos de la entrevista cualitativa. El muestreo, la recopilación de datos y el análisis se realizaron de forma simultánea e iterativa hasta que se logró la saturación de datos. RESULTADOS: Se entrevistaron 24 pacientes; 19 en las que la indicación quirúrgica fue por cáncer y 5 por reducción de riesgo. La mediana del tiempo entre la pérdida del implante y la entrevista fue de 42 (rango 22-52) meses. Diez mujeres se habían sometido a una reconstrucción secundaria; dos estaban a la espera de la cirugía y 12 habían rechazado la reconstrucción posterior. Se identificaron tres temas clave, siendo las necesidades de: i) información precisa sobre los riesgos y beneficios de la IBBR, ii) más información sobre los signos de "alarma precoz" de las complicaciones postoperatorias que permitiesen a las mujeres buscar ayuda, y iii) mejor soporte tras la pérdida de la prótesis. CONCLUSIÓN: La pérdida de una prótesis es una complicación catastrófica para muchas mujeres. Una mejor información y apoyo preoperatorios, junto con una atención holística centrada en la paciente cuando se presentan las complicaciones, podrían mejorar significativamente la experiencia y el resultado de la atención.

Pluto's Interaction With Energetic Heliospheric Ions.

Pluto energies of a few kiloelectron volts and suprathermal ions with tens of kiloelectron volts and above. We measure this population using the Pluto Energetic Particle Spectrometer Science Investigation (PEPSSI) instrument on board the New Horizons spacecraft that flew by Pluto in 2015. Even though the measured ions have gyroradii larger than the size of Pluto and the cross section of its magnetosphere, we find that the boundary of the magnetosphere is depleting the energetic ion intensities by about an order of magnitude close to Pluto. The intensity is increasing exponentially with distance to Pluto and reaches nominal levels of the interplanetary medium at about 190R P distance. Inside the wake of Pluto, we observe oscillations of the ion intensities with a periodicity of about 0.2 hr. We show that these can be quantitatively explained by the electric field of an ultralow-frequency wave and discuss possible physical drivers for such a field. We find no evidence for the presence of plutogenic ions in the considered energy range.

Profiling microRNAs in individuals at risk of progression to rheumatoid arthritis.

BACKGROUND: Individuals at risk of rheumatoid arthritis (RA) demonstrate systemic autoimmunity in the form of anti-citrullinated peptide antibodies (ACPA). MicroRNAs (miRNAs) are implicated in established RA. This study aimed to (1) compare miRNA expression between healthy individuals and those at risk of and those that develop RA, (2) evaluate the change in expression of miRNA from "at-risk" to early RA and (3) explore whether these miRNAs could inform a signature predictive of progression from "at-risk" to RA. METHODS: We performed global profiling of 754 miRNAs per patient on a matched serum sample cohort of 12 anti-cyclic citrullinated peptide (CCP) + "at-risk" individuals that progressed to RA. Each individual had a serum sample from baseline and at time of detection of synovitis, forming the matched element. Healthy controls were also studied. miRNAs with a fold difference/fold change of four in expression level met our primary criterion for selection as candidate miRNAs. Validation of the miRNAs of interest was conducted using custom miRNA array cards on matched samples (baseline and follow up) in 24 CCP+ individuals; 12 RA progressors and 12 RA non-progressors. RESULTS: We report on the first study to use matched serum samples and a comprehensive miRNA array approach to identify in particular, three miRNAs (miR-22, miR-486-3p, and miR-382) associated with progression from systemic autoimmunity to RA inflammation. MiR-22 demonstrated significant fold difference between progressors and non-progressors indicating a potential biomarker role for at-risk individuals. CONCLUSIONS: This first study using a cohort with matched serum samples provides important mechanistic insights in the transition from systemic autoimmunity to inflammatory disease for future investigation, and with further evaluation, might also serve as a predictive biomarker.

Evaluating the risk of pneumonia with inhaled corticosteroids in COPD: Retrospective database studies have their limitations SA.

An increased risk of non-fatal pneumonia has been documented in COPD patients treated with inhaled corticosteroids (ICS) in randomized clinical trials. Retrospective database analyses have been conducted to evaluate this signal in larger populations treated in the community. To understand how methodological choices may influence results in observational studies, we compared two recent Canadian studies which used health administrative databases from Quebec and Ontario and came to opposite conclusions on the risk of pneumonia in ICS treated COPD patients. Explanations for why the results of these studies diverged are explored. The Suissa analysis used RAMQ data from Quebec and showed an increased relative risk of serious pneumonia for current users of ICS compared to non users, RR = 1.69 (95% confidence interval, 1.63-1.75). The Gershon analysis used ODB data and showed no difference for pneumonia hospitalisation, RR = 1.01 (0.93-1.08). Reasons for differences in study findings include lack of validated definitions of COPD, poor selection of relevant exposure groups, channeling and confounding biases, and failure to perform on-treatment analyses for safety. CONCLUSION: Our study identifies methodological features that need consideration to increase robustness and minimize threats to internal validity of retrospective health administrative database studies.

Serological biomarker screening and host factor analysis elucidating immune response heterogeneity in active pulmonary tuberculosis.

While mortality and morbidity from pulmonary tuberculosis (PTB) have improved, diagnosis of this infectious disease remains suboptimal without a point-of-care test. Antibody/ antigen-based serodiagnostics is the most amenable for point-of-care translation but hampered by a lack of validated biomarkers and a heterogeneous patient antibody response. Using a case-control design, we assessed serodiagnostic potential of immunoglobulins G, A, and dimeric IgA responses against 18 antigenic preparations, followed by antibody-subclass responses against antigen 60 (A60), and four markers of host innate immunity by enzymelinked immunoassay using sera samples (n=110) collected from April to October 2007 in VietNam from human immunodeficiency-negative patients with provisional diagnosis of PTB. We further analyzed host variables to investigate factors driving biomarker heterogeneity observed in patients. Among active pulmonary tuberculosis patients, low correlation was observed between anti-A60 antibody-classes, and between anti-A60 immunoglobulin G subclasses, but anti-A60 immunoglobulin A subclasses were significantly correlated. The best diagnostic combination of anti-A60 immunoglobulin G/A and a C-reactive protein "ruleout" remains insufficient at 82%/92% sensitivity/specificity (95%CI: 72-92%/82-98%). Heterogeneity of anti-A60 immunoglobulins G2, G3, M, as well as C-reactive protein and serum amyloid A levels observed in this study population appeared to be significantly associated with history of previous tuberculosis, hemoptysis, age, vaccination, night sweats, smoking, chest pain, fever, alcohol, and solid culture count. Further research on tuberculosis serological biomarkers may require consideration of host factors and new approaches using multiple biomarkers.

Serological biomarker screening and host factor analysis elucidating immune response heterogeneity in active pulmonary tuberculosis

While mortality and morbidity from pulmonary tuberculosis (PTB) have improved, diagnosis of this infectious disease remains suboptimal without a point-of-care test. Antibody/ antigen-based serodiagnostics is the most amenable for point-of-care translation but hampered by a lack of validated biomarkers and a heterogeneous patient antibody response. Using a case-control design, we assessed serodiagnostic potential of immunoglobulins G, A, and dimeric IgA responses against 18 antigenic preparations, followed by antibody-subclass responses against antigen 60 (A60), and four markers of host innate immunity by enzymelinked immunoassay using sera samples (n=110) collected from April to October 2007 in VietNam from human immunodeficiency-negative patients with provisional diagnosis of PTB. We further analyzed host variables to investigate factors driving biomarker heterogeneity observed in patients. Among active pulmonary tuberculosis patients, low correlation was observed between anti-A60 antibody-classes, and between anti-A60 immunoglobulin G subclasses, but anti-A60 immunoglobulin A subclasses were significantly correlated. The best diagnostic combination of anti-A60 immunoglobulin G/A and a C-reactive protein “ruleout” remains insufficient at 82%/92% sensitivity/specificity (95%CI: 72-92%/82-98%). Heterogeneity of anti-A60 immunoglobulins G2, G3, M, as well as C-reactive protein and serum amyloid A levels observed in this study population appeared to be significantly associated with history of previous tuberculosis, hemoptysis, age, vaccination, night sweats, smoking, chest pain, fever, alcohol, and solid culture count. Further research on tuberculosis serological biomarkers may require consideration of host factors and new approaches using multiple biomarkers.

Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

BACKGROUND: Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. HYPOTHESIS/OBJECTIVES: To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. ANIMALS: Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). METHODS: Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed. RESULTS: Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles. CONCLUSIONS AND CLINICAL IMPORTANCE: Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates.

Infection prevention in breast implant surgery - A review of the surgical evidence, guidelines and a checklist.

INTRODUCTION: As a result of increasing use of implant-based breast reconstruction, complications such as infection are being encountered more frequently. Surgical Site Infections (SSIs) cause morbidity for the patient, can lead to capsular contracture or implant loss and are costly to healthcare systems. National Guidelines suggesting methods to reduce SSI related complications have been produced, but are limited in the scope of interventions covered and underlying evidence presented. METHODS: We performed a literature review encompassing a wide variety of possible SSI prevention strategies. We aimed to present summaries of the available evidence and give pragmatic recommendations as to their validity to use as guidelines for infection prevention strategies for implant-based breast reconstruction. RESULTS: A lack of high quality data relating to the benefit of SSI prevention strategies in implant-based breast reconstruction exists. Many papers relate to orthopaedic implant surgery, or clean surgery in general. Following review of the evidence, sufficient data exists to support use of perioperative antibiotics at implant-based breast reconstruction, with continuation for an extended period in "high risk" patients. Alcohol containing skin preparations should be used over aqueous solutions. Laminar air flow use is suggested. Theatre traffic should be kept to a minimum, as should duration of operative procedure. The implant pocket should be washed prior to implantation. Double gloving and conductive warming are also endorsed. CONCLUSIONS: We have produced a perioperative "Theatre Implant Checklist" for SSI prevention in implant-based breast surgery, with a set of pragmatic up to date guidelines, which allows the reader to evaluate the evidence upon which our recommendations are based.

Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis.

REASONS FOR PERFORMING STUDY: Although exertional rhabdomyolysis (ER) is common in Arabian horses, there are no dedicated studies describing histopathological characteristics of muscle from Arabian horses with ER. OBJECTIVES: To prospectively identify distinctive histopathological features of muscle from Arabian endurance horses with a history of ER (pro-ER) and to retrospectively determine their prevalence in archived samples from Arabian horses with exertional myopathies (retro-ER). STUDY DESIGN: Prospective and retrospective histopathological description. METHODS: Middle gluteal muscle biopsies obtained from Arabian controls (n = 14), pro-ER (n = 13) as well as archived retro-ER (n = 25) muscle samples previously classified with type 2 polysaccharide storage myopathy (15/25), recurrent exertional rhabdomyolysis (7/25) and no pathology (3/25) were scored for histopathology and immunohistochemical staining of cytoskeletal proteins. Glutaraldehyde-fixed samples (2 pro-ER, one control) were processed for electron microscopy. Pro-ER and retro-ER groups were compared with controls using Mann-Whitney U and Fisher's exact tests. RESULTS: Centrally located myonuclei in mature myofibres were found in significantly more (P<0.05) pro-ER (12/13) and retro-ER (21/25) horses than controls (4/14). Degenerating myofibres were not evident in any biopsies. Retro-ER horses had amylase-resistant polysaccharide (6/25, P<0.05) and higher scores for cytoplasmic glycogen, rimmed vacuoles and rod-like bodies. A few control horses (3/14) and significantly (P<0.05) more pro-ER (12/13) and retro-ER (18/25) horses had disrupted myofibrillar alignment and large desmin and αß-crystallin positive cytoplasmic aggregates. Prominent Z-disc degeneration and focal myofibrillar disruption with regional accumulation of ß-glycogen particles were identified on electron microscopy of the 2 pro-ER samples. CONCLUSIONS: In a subset of Arabian horses with intermittent episodes of exertional rhabdomyolysis, ectopic accumulation of cytoskeletal proteins and Z-disc degeneration bear a strong resemblance to a myofibrillar myopathy. While many of these horses were previously diagnosed with type 2 polysaccharide storage myopathy, pools of glycogen forming within disrupted myofibrils appeared to give the false appearance of a glycogen storage disorder.

The Equine Movement Disorder "Shivers" Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration.

"Shivers" is a progressive equine movement disorder of unknown etiology. Clinically, horses with shivers show difficulty walking backward, assume hyperflexed limb postures, and have hind limb tremors during backward movement that resembles shivering. At least initially, forward movements are normal. Given that neither the neurophysiologic nor the pathologic mechanisms of the disease is known, nor has a neuroanatomic locus been identified, we undertook a detailed neuroanatomic and neuropathologic analysis of the complete sensorimotor system in horses with shivers and clinically normal control horses. No abnormalities were identified in the examined hind limb and forelimb skeletal muscles nor the associated peripheral nerves. Eosinophilic segmented axonal spheroids were a common lesion. Calretinin-positive axonal spheroids were present in many regions of the central nervous system, particularly the nucleus cuneatus lateralis; however, their numbers did not differ significantly from those of control horses. When compared to controls, calretinin-negative, calbindin-positive, and glutamic acid decarboxylase-positive spheroids were increased 80-fold in Purkinje cell axons within the deep cerebellar nuclei of horses with shivers. Unusual lamellar or membranous structures resembling marked myelin decompaction were present between myelin sheaths of presumed Purkinje cell axons in the deep cerebellar nuclei of shivers but not control horses. The immunohistochemical and ultrastructural characteristics of the lesions combined with their functional neuroanatomic distribution indicate, for the first time, that shivers is characterized by end-terminal neuroaxonal degeneration in the deep cerebellar nuclei, which results in context-specific hypermetria and myoclonus.

Molecular phenotypes of DCIS predict overall and invasive recurrence.

BACKGROUND: Molecular phenotypes of invasive breast cancer predict early recurrence. Ductal carcinoma in situ (DCIS) exhibits similar phenotypes, but their frequency and significance remain unclear. To determine whether DCIS molecular phenotypes predict recurrence, 314 women (median age 57.7 years) with primary DCIS who were screened or entered DCIS trials in a specialist breast unit from 1990 to 2010 were studied. PATIENTS AND METHODS: Expression of Ki67, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) within primary DCIS was established using immunohistochemistry (IHC). Patients were subdivided into molecular phenotypes using IHC surrogates [Luminal A (ER/PR+HER2-), Luminal B (ER/PR+/HER2+), HER2 type (ER and PR-/HER2+) or triple negative (ER/PR/HER2)] and recurrence rates compared. RESULTS: Overall, there were 57 (18.2%) recurrences, 35 (11.2%) DCIS and 22 (7%) invasive cancer. A low rate of recurrence at 5 years was seen in Luminal A DCIS (7.6%), compared with 15.8%-36.1% in other phenotypes. Independent predictors of overall recurrence on multivariate analysis were involved (<1 mm) surgical margins (HR 4.31, P < 0.001), high-grade lesions (HR 2.28, P < 0.024) and molecular phenotype (HR 5.14, P = 0.001 for Luminal B; HR 6.46, P < 0.001 for HER2 type and HR 3.27, P = 0.028 for triple-negative disease compared with Luminal A DCIS). Independent predictors for invasive recurrence were high Ki67 expression (HR 1.04, P = 0.021) and molecular phenotype (HR 13.4, P = 0.014 for Luminal B; HR 11.4, P = 0.027 for HER2 type and HR 10.3, P = 0.031 for triple negative compared with Luminal A DCIS). CONCLUSIONS: DCIS molecular phenotype predicts for both overall and invasive recurrence. HER2 testing of DCIS could help clinicians individualise the treatment of patients with DCIS.

Characterisation of an OCS-dependent severe asthma population treated with mepolizumab.

UNLABELLED: A subpopulation of patients with asthma treated with maximal inhaled treatments is unable to maintain asthma control and requires additional therapy with oral corticosteroids (OCS); a subset of this population continues to have frequent exacerbations. Alternate treatment options are needed as daily use of OCS is associated with significant systemic adverse effects that affect many body systems and have a direct association with the dose and duration of OCS use. We compared the population demographics, medical conditions and efficacy responses of the OCS-dependent group from the DREAM study of mepolizumab with the group not managed with daily OCS. TRIAL REGISTRATION NUMBER: NCT01000506.

Diagnosis and assessment of disease activity in takayasu arteritis: a childhood case illustrating the challenge.

Takayasu Arteritis (TA) is a rare, debilitating large vessel vasculitis occurring in patients of all ages, including infants, but the disease most commonly presents in the third decade. Diagnosis is often delayed and consequently TA is associated with significant morbidity and mortality. Accurate methods of monitoring disease activity or damage are lacking and currently rely on a combination of clinical features, blood inflammatory markers, and imaging modalities. In this report we describe a case of a 14-year-old boy with childhood-onset TA who, despite extensive negative investigations, did indeed have on-going active large vessel vasculitis with fatal outcome. Postmortem analysis demonstrated more extensive and active disease than originally identified. This report illustrates and discusses the limitations of current modalities for the detection and monitoring of disease activity and damage in large vessel vasculitis. Clinicians must be aware of these limitations and challenges if we are to strive for better outcomes in TA.

The frequency of presentation and clinico-pathological characteristics of symptomatic versus screen detected ductal carcinoma in situ of the breast.

INTRODUCTION: DCIS accounts for 20% of screen-detected breast cancers, but also presents symptomatically. Historically, approximately 5% of DCIS was thought to be symptomatic, but accurate evaluation of the presentation of symptomatic DCIS is needed to determine its incidence and tumour biology. METHODS: Clinico-pathological details of a consecutive series of patients presenting to a single breast-unit, with a pre-operative diagnosis of DCIS, were selected. Data included age, mode of presentation, pre-operative clinical and radiographical findings. The final tumour histology, operation, size, grade, ER status (and HER2 expression in invasive cases) were recorded. RESULTS: 375 patients had a pre-operative histological diagnosis of DCIS. 308 (82%) screen-detected (median age 59), 67 (18%) presented via symptomatic clinics (median age 50). At final histology 286 (74%) were pure DCIS, and 67 (23%) had an invasive focus. 43% (29/67) of symptomatic cases had an invasive focus at final histology versus 19% (60/308) screen-detected (p ≤ 0.001). 31% (9/29) of symptomatic, versus 10% (6/60) of screen-detected cases with invasion were node positive (p = 0.05). 45% (28/62) intermediate/high-grade symptomatic cases had an invasive focus at final histology, compared to 19% (57/297) intermediate/high-grade screen-detected cases. 86% (212/248) screen-detected pure DCIS was ER positive compared to 68% (26/38) symptomatically presenting pure DCIS (p ≤ 0.001). Overall, 13% (38/248) pure DCIS presented symptomatically (p = 0.001). CONCLUSIONS: Overall, thirteen percent of pure DCIS present symptomatically. Nearly half of symptomatically presenting DCIS at core biopsy has an occult invasive focus and is more frequently ER negative. Symptomatic DCIS with an invasive focus is more likely to have lymph node involvement.

Contribution of the ethics committee of the French society of intensive care medicine to a scenario for the implementation of organ donation after Maastricht III-type cardiac death in France.

French law allows organ donation after death due to cardiocirculatory arrest. In the Maastricht classification, type III non-heart-beating donors are those who experience cardiocirculatory arrest after the withdrawal of life-sustaining treatments. French authorities in charge of regulating organ donation (Agence de la Biomédecine, ABM) are considering organ collection from Maastricht type III donors. We describe a scenario for Maastricht type III organ donation that fully complies with the ethical norms governing care to dying patients. That organ donation may occur after death should have no impact on the care given to the patient and family. The dead-donor rule must be followed scrupulously: the organ retrieval procedure must neither cause nor hasten death. The decision to withdraw life-sustaining treatments, withdrawal modalities, and care provided to the patient and family must adhere strictly to the requirements set forth in patient-rights legislation (the 2005 Léonetti law in France) and should not be influenced in any way by the possibility of organ donation. A major ethical issue regarding the family is how best to transition from discussing treatment-withdrawal decisions to discussing possible organ retrieval for donation should the patient die rapidly after treatment withdrawal. Close cooperation between the healthcare team and the organ retrieval team is crucial to minimize the distress of family members during this transition. Modalities for implementing Maastricht type III organ donation are discussed here, including the best location for withdrawing life-sustaining treatments (operating room or intensive care unit).