Metaplastic carcinoma of the breast : Prognosis and response to systemic treatment in metastatic disease

Background: Metaplastic breast carcinomas (MpBCs) are rare, aggressive breast cancers. Due to the scant literature of this disease most guidelines do not give recommendation for this entity. The aim of the study was to review the clinicopathologic features, treatment, and outcomes of the patients with MpBC treated at our institution. Material and methods: We searched databases for patients with histologically confirmed MpBC from 2002 to 2016. Results: A total of 78 patients with MpBC were included in the study. All histological material was reviewed by an experienced breast pathologist. Most tumors were grade 3 (83%) and triple negative (85%). Eighty-two percent were node negative. Sixty-four percent received adjuvant chemotherapy. The 5-year disease free survival was 63% and 5-year breast cancer specific overall survival was 61%. Tumor size and mixed metaplastic histology were associated with worse outcome in this patient group. One third of the patients (n = 28) had metastatic disease at initial presentation or developed metastases at follow-up. The lungs were the most common site of first distant recurrence. Half (n = 14) of these patients received palliative chemotherapy. Of those only 6% (n = 2) had partial response and 18% had stable disease as best response to treatment. The median overall survival time with metastatic disease was only 3.4 months. Conclusion: MpBC is an aggressive type of breast cancer with poor outcome despite low nodal involvement and aggressive local and systemic therapy. Tumor response to palliative systemic chemotherapy remains poor for MpBC patients.Peer reviewe

Statin use and vitreoretinal surgery : Findings from a Finnish population-based cohort study

PurposeVitreoretinal (VR) surgery is the third most common intraocular surgery after refractive and cataract surgery. The impact of statin therapy on VR surgery outcomes remains unclear, despite a potentially beneficial effect. We explored the association of preoperative statin therapy and the need for revitrectomy after primary vitrectomy. MethodsOur historical, population-based, register-based, VR surgery cohort consisted of 5709 patients operated in a tertiary, academic referral hospital in Finland, during 2008-2014, covering 6.5years. Subgroup analysis was performed as follows: eyes operated due to (i) rhegmatogenous retinal detachment (RRD), (ii) VR interface diseases (macular pucker/hole), (iii) diabetic maculopathy or proliferative retinopathy, (iv) vitreous haemorrhage, (v) lens subluxation, (vi) vitreous opacities or (vii) other VR indication. The primary end-point event was revitrectomy during a postoperative follow-up period of 1year due to retinal redetachment, vitreous rehaemorrhage, postoperative endophthalmitis, recurrent pucker or unclosed macular hole. ResultsRhegmatogenous retinal detachment (RRD) was the second most frequent indication of VR surgery, including 1916 patients, with 305 re-operations with rate 0.20 (95% CI 0.18-0.23) per person-year. Statin treatment in time of operation was associated with lower risk of re-operation according to relative scale (incidence rate ratio 0.72, 95% CI 0.53-0.97), but not in absolute scale (incidence rate difference -0.58, 95% CI -4.30 to 3.15 for 100 person-years). No association with statin therapy and vitrectomy outcome was observed in the other VR subgroups. ConclusionUse of statin treatment was associated with a 28% lower risk of revitrectomy in patients operated due to RRD. Further randomized clinical trials are highly warranted.Peer reviewe

Primary neuroendocrine breast carcinomas are associated with poor local control despite favourable biological profile : a retrospective clinical study

Background: Breast carcinomas with neuroendocrine features (NEBC) are a very rare entity of mammary neoplasms, WHO classification of which has recently been revised. There are very limited data available about the clinical behaviour and treatment options of NEBC. Methods: We collected retrospectively patients with NEBC from Oulu and Helsinki University Hospitals in 2007-2015. There were 43 NEBC cases during the period. Results: The incidence of NEBC from all breast cancers varied from 0.1% in Helsinki to 1.3% in Oulu. The mean tumor size was 2.2 cm and 23 patients (55.8%) had no lymph node metastases when diagnosed. In total, 4 patients (9.3%) had distant metastases at the time of diagnosis. High estrogen receptor (ER) expression was observed in 41 (97.7%) patients. When non-metastatic NEBC were compared to a prospective set of ductal carcinomas (n = 506), NEBC were more often HER2 negative (p = 0.046), ER positive (p = 0.0062) and the NEBC patients were older (p <0.0005) than patients with ductal carcinomas. Plasma chromogranin A correlated only to higher age at diagnosis (p = 0. 0028). Relapse-free survival (p = 0.0013), disease-free survival (p = 0.024) and overall survival (p = 0.0028) favoured ductal carcinomas compared to NEBC, while no difference was observed in distant disease-free survival or in breast cancer-specific survival. Conclusions: There is remarkable variation in the incidence of NEBC in Finland, which is likely to be explained by differences in the use of neuroendocrine marker immunostainings. Poor local control and worse overall survival may be linked to the more aggressive biology of the disease, despite its association with apparently indolent prognostic factors.Peer reviewe

Targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) : study protocol and statistical analysis plan for a randomized controlled trial

Background: Septic shock has a 90-day mortality risk of up to 50 %. The hemodynamic targets, including mean arterial pressure (MAP) are not based on robust clinical data. Both severe hypotension and high doses of vasopressors may be harmful. Hence, re-evaluation of hemodynamic targets in septic shock is relevant. Methods/design: The targeted tissue perfusion versus macrocirculation-guided standard care in patients with septic shock (TARTARE-2S) trial is a prospective, two-parallel-group, randomized, open-label, multicenter trial with assessor-blinded outcome evaluation. We will randomize at least 200 patients with septic shock in four European intensive care units (ICUs) to test whether a tissue perfusion-guided treatment strategy based on capillary refill time, peripheral temperature, arterial lactate concentrations, and accepting lower MAP levels, leads to a faster resolution of shock than macrocirculation target-guided standard care. The primary outcome measure is days alive in 30 days with normal arterial blood lactate (first value of Discussion: The TARTARE-2S trial will provide important clinical data on treatment targets in septic shock, evaluating the impact of clinical tissue perfusion-guided hemodynamic treatment on a surrogate outcome combining resolution of shock (hyperlactatemia and vasopressors/inotropes), and 30-day mortality.Peer reviewe

Preface to the special issue on Monitoring and Modelling of Carbon-Balance-, Water- and Snow-Related Phenomena at Northern Latitudes

201

A realist analysis of hospital patient safety in Wales:Applied learning for alternative contexts from a multisite case study

Background: Hospital patient safety is a major social problem. In the UK, policy responses focus on the introduction of improvement programmes that seek to implement evidence-based clinical practices using the Model for Improvement, Plan-Do-Study-Act cycle. Empirical evidence that the outcomes of such programmes vary across hospitals demonstrates that the context of their implementation matters. However, the relationships between features of context and the implementation of safety programmes are both undertheorised and poorly understood in empirical terms. Objectives: This study is designed to address gaps in conceptual, methodological and empirical knowledge about the influence of context on the local implementation of patient safety programmes. Design: We used concepts from critical realism and institutional analysis to conduct a qualitative comparative-intensive case study involving 21 hospitals across all seven Welsh health boards. We focused on the local implementation of three focal interventions from the 1000 Lives+ patient safety programme: Improving Leadership for Quality Improvement, Reducing Surgical Complications and Reducing Health-care Associated Infection. Our main sources of data were 160 semistructured interviews, observation and 1700 health policy and organisational documents. These data were analysed using the realist approaches of abstraction, abduction and retroduction. Setting: Welsh Government and NHS Wales. Participants: Interviews were conducted with 160 participants including government policy leads, health managers and professionals, partner agencies with strategic oversight of patient safety, advocacy groups and academics with expertise in patient safety. Main outcome measures: Identification of the contextual factors pertinent to the local implementation of the 1000 Lives+ patient safety programme in Welsh NHS hospitals. Results: An innovative conceptual framework harnessing realist social theory and institutional theory was produced to address challenges identified within previous applications of realist inquiry in patient safety research. This involved the development and use of an explanatory intervention–context–mechanism–agency–outcome (I-CMAO) configuration to illustrate the processes behind implementation of a change programme. Our findings, illustrated by multiple nested I-CMAO configurations, show how local implementation of patient safety interventions are impacted and modified by particular aspects of context: specifically, isomorphism, by which an intervention becomes adapted to the environment in which it is implemented; institutional logics, the beliefs and values underpinning the intervention and its source, and their perceived legitimacy among different groups of health-care professionals; and the relational structure and power dynamics of the functional group, that is, those tasked with implementing the initiative. This dynamic interplay shapes and guides actions leading to the normalisation or the rejection of the patient safety programme. Conclusions: Heightened awareness of the influence of context on the local implementation of patient safety programmes is required to inform the design of such interventions and to ensure their effective implementation and operationalisation in the day-to-day practice of health-care teams. Future work is required to elaborate our conceptual model and findings in similar settings where different interventions are introduced, and in different settings where similar innovations are implemented. Funding: The National Institute for Health Research Health Services and Delivery Research programme