Validation of the Helsinki University Hospital prevent pressure Injury Risk Assessment Tool : a prospective observational study

Background Pressure injures are a common adverse event in a hospital, and they are one of the most important quality indicators of patient care. Risk assessment is recommended as the first step in the prevention of pressure injuries. A Prevent Pressure Injury Risk Assessment Tool is a new tool for risk assessment that was developed by the Helsinki University Hospital. Aim The aim of this study was to evaluate the predictive validity and the concurrent validity of the Prevent Pressure Injury Risk Assessment Tool in acute care. Method The prospective observational study was conducted in 19 in-patient wards representing internal medicine, neurology, and surgery during 2017-2018. The participants' inclusion criteria were: age >= 18 years old, no pressure injury on admission to the hospital and consenting to participate. The data collected by physical assessment of patients was combined with data from electronic patient records. Each patient was assessed by two different nurses with the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale at patient admission. Furthermore, skin condition was observed throughout the hospital stay. Results Of the 637 patients accepted for the study, 10 (1.6%) developed a pressure injury during the hospital stay. Poisson regression analysis showed that pressure injuries were more likely in high-risk patients compared to those with low-risk. The sensitivity of the Prevent Pressure Injury Risk Assessment Tool was adequate (75%), while specificity was poor (40%). A moderate correlation was found between the Prevent Pressure Injury Risk Assessment Tool and the Braden Scale. Conclusions The Prevent Pressure Injury Risk Assessment Tool may be useful for identifying the adult pressure injury risk patients in acute care. Further research is needed to evaluate interrater reliability, and usability and validity with different patient populations.Peer reviewe

Core Needle Biopsy Enhances the Activity of the CCL2/CCR2 Pathway in the Microenvironment of Invasive Breast Cancer

The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative biopsies to increase tumor supportive elements in the microenvironment, whereas, in humans, the impact of CNB on the host’s immunologic response has not been investigated. In this pilot study, we compared the expression of CCL2/CCR2 pathway components at the protein level in samples from CNBs to those from the corresponding resected tumors from 52 patients with primary breast cancer. We found an increased expression of CD163, CD14 and CCR2 in monocytes/macrophages and a slight decrease of CCL2 in the malignant epithelium in the tumors after the biopsy. The increased infiltration of immunosuppressive monocytes/macrophages and the decreased tumor cell CCL2 expression, presumably due to the CCR2 availability-dependent CCL2 internalization, suggest that CNB enhances the activity of the CCL2/CCR2 pathway, and this finding warrants confirmatory examination. The switch in the context-dependent role of CCL2 on the polarization of macrophages may lead to increased tumor supportive function both locally and in the peripheral immune machinery. The future directions in breast cancer should include early interventions to support the tumor surveillance of the host

Searching for degenerate Higgs bosons using a profile likelihood ratio method

ATLAS and CMS collaborations at the Large Hadron Collider have observed a new resonance consistent with the standard model Higgs boson. However, it has been suggested that the observed signal could also be produced by multiple nearly mass-degenerate states that couple differently to the standard model particles. In this work, a method to discriminate between the hypothesis of a single Higgs boson and that of multiple mass-degenerate Higgs bosons was developed. Using the matrix of measured signal strengths in different production and decay modes, parametrizations for the two hypotheses were constructed as a general rank 1 matrix and the most general 5 x 4 matrix, respectively. The test statistic was defined as a ratio of profile likelihoods for the two hypotheses. The method was applied to the CMS measurements. The expected test statistic distribution was estimated twice by generating pseudo-experiments according to both the standard model hypothesis and the single Higgs boson hypothesis best fitting the data. The p-value for the single Higgs boson hypothesis was defined from both expected test statistic distributions, and it was (8.0 ± 0.3)% and (11.0±0.3)%, respectively. In addition to this, a p-value was also estimated in an alternative way using a χ2 distribution, fitted to the pseudo-experiments for the standard model Higgs boson hypothesis. The resulting p-value was 10.8%. Thus the three estimates yield similar p-values for the single Higgs boson hypothesis. These results suggest that the CMS data is compatible with the single Higgs boson hypothesis, as in the standard model. Furthermore, the result is insensitive to choice of the single Higgs boson hypothesis used to derive it, and it does not depend on the precise shape of the test statistic distribution. The developed method can be applied also to other arbitrarily-sized matrices, and it takes into account the uncertainties on the measurements, missing elements of data, and possible correlations. This thesis is an extensive description of the method that has also been published in EPJC (David, Heikkilä and Petrucciani), and the method has been used in the final Run 1 Higgs combination and properties article (CMS Collaboration, incl. Heikkilä).Suuren hadronitörmäyttimen kaksi koetta, ATLAS ja CMS, ovat havainneet uuden hiukkasen, joka on standardimallin Higgsin bosonin kaltainen. On kuitenkin ehdotettu, että havaittu signaali voisi aiheutua useasta, lähes samanmassaisista hiukkasista, jotka kytkeytyvät eri vahvuuksilla standardimallin hiukkasiin. Työssä kehitettiin menetelmä, jonka avulla voidaan tutkia kuinka hyvin hypoteesi yhdestä Higgsin bosonista sopii mittaustuloksiin verrattuna hypoteesiin samanmassaisista Higgsin bosoneista. Nollahypoteesi ja yleinen hypoteesi parametrisoitiin vastaavasti asteen 1 matriisina sekä yleisimpänä 5 x 4 matriisina. Testisuure määriteltiin osamäärätestisuureen, eli hypoteesejä vastaavien uskottavuusfunktioiden suhdeluvun, avulla. Menetelmää sovellettiin CMS-mittauksiin.Testisuureen odotettua jakaumaa arvioitiin näennäiskokeilla, jotka luotiin kahta lähtöasetelmaa - standardimallia sekä suurimman uskottavuuden estimaatteja - käyttäen. P-arvo nollahypoteesin mukaisessa tilanteessa määritettiin molemmista testisuureen odotetuista jakaumista ja saadut p-arvot olivat vastaavasti (8.0 ± 0.3)% sekä (11.0 ± 0.3)%. P-arvo määritettiin myös vaihtoehtoisella tavalla, jossa χ2 -jakauma sovitettiin siihen testisuureen odotettuun jakaumaan, joka arvioitiin standardimallin mukaisilla näennäiskokeilla. Tällöin p-arvo oli 10.8%. Tuloksena saadut kolme p-arvoa olivat näin ollen samansuuruisia. Saadut tulokset osoittavat, että CMS-mittaustulokset ovat yhteensopivia nollahypoteesin eli yhden Higgsin bosonin hypoteesin kanssa, aivan kuten standardimallissa. Huomioitakoon, että saatu p-arvo ei riipu näennäiskokeiden luomiseen valitusta lähtöasetelmasta tai testisuureen odotetun jakauman tarkasta muodosta. Työssä kehitettyä menetelmää voidaan soveltaa myös muihin mielivaltaisen kokoisiin matriiseihin, ja se huomioi mittausten virheet, puuttuvat mittaukset sekä mahdolliset korrelaatiot. Tämä työ on laajempi kuvaus menetelmästä, joka on myös julkaistu EPJC:ssä (David, Heikkilä ja Petrucciani) ja jota on käytetty CMS-kokeen lopullisessa Run 1 Higgs-kombinaatiojulkaisussa (CMS-kollaboraatio, ml. Heikkilä)

Quantities of CD3+, CD8+and CD56+lymphocytes decline in breast cancer recurrences while CD4+remain similar

Peer reviewe

High expression of CCL2 in tumor cells and abundant infiltration with CD14 positive macrophages predict early relapse in breast cancer

Macrophages are important for the function of the innate immune system, and in solid tumors, they represent a significant proportion of the tumor mass. Tumor-associated macrophages (TAM) have a M2 phenotype and show a multitude of pro-tumoral functions, promoting tumor cell survival, proliferation, and dissemination. CCL2, synthesized by tumor and stromal cells, initiates a chemokine cascade inducing these processes. We studied by immunohistochemistry (IHC) the frequency of TAMs and CCL2 expressing cells in three groups of primary tumor (PT)-recurrence (R) pairs, where relapse was recorded within 2years (group 1), between 5 and 10years (group 2), and after 10years (group 3). In our study all established breast cancers were heavily infiltrated by CD68 positive cells. Both in PTs and in R lesions the infiltration was more abundant in the peritumoral than in the intratumoral stroma. The mean frequency of M2 marker and CD14 positive cells in the intratumoral stroma and CCL2 expressing tumor cells was higher in the Rs as compared to the corresponding PTs. In PTs, a high frequency of CD14 positive cells and a high expression of CCL2 by tumor cells was associated with an early recurrence. The findings support the current understanding of immune cell orchestrated development, progression and metastatic spread of breast cancer. Our study showed that a high frequency of CCL2 positive tumor cells and CD14 positive TAMs are significant risk factors for rapid tumor recurrence. Potential targets for intervention are discussed.Peer reviewe

Clever-1 positive macrophages in breast cancer

Purpose Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically, how Clever-1 + macrophages correlate with clinicopathologic factors, Tumor Infiltrating Lymphocytes (TILs) and prognosis. Methods Tissue microarray blocks were made from 373 primary breast cancer operation specimens. Hematoxylin and Eosin (H&E-staining) and immunohistochemical staining with Clever-1, CD3, CD4 and CD8 antibodies were performed. Differences in quantities of Clever-1 + macrophages and TILs were analyzed. Clever-1 + cell numbers were correlated with 25-year follow-up survival data and with breast cancer clinicopathologic parameters. Results Low numbers of intratumoral Clever-1 + cells were found to be an independent adverse prognostic sign. Increased numbers of Clever-1 + cells were found in high grade tumors and hormone receptor negative tumors. Tumors that had higher amounts of Clever-1 + cells also tended to have higher amounts of TILs. Conclusion The association of intratumoral Clever-1 + macrophages with better prognosis might stem from the function of Clever as a scavenger receptor that modulates tumor stroma. The association of Clever-1 + macrophages with high number of TILs and better prognosis indicates that immunosuppression by M2 macrophages is not necessarily dampening adaptive immune responses but instead keeping them in control to avoid excess inflammation.Peer reviewe

Histopathological features of breast tumours in BRCA1, BRCA2 and mutation-negative breast cancer families

INTRODUCTION: Histopathological features of BRCA1 and BRCA2 tumours have previously been characterised and compared with unselected breast tumours; however, familial non-BRCA1/2 tumours are less well known. The aim of this study was to characterise familial non-BRCA1/2 tumours and to evaluate routine immunohistochemical and pathological markers that could help us to further distinguish families carrying BRCA1/2 mutations from other breast cancer families. METHODS: Breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2 and 74 non-BRCA1/2 families were studied on a tumour tissue microarray. Immunohistochemical staining of oestrogen receptor (ER), progesterone receptor (PgR) and p53 as well as the histology and grade of these three groups were compared with each other and with the respective information on 862 unselected control patients from the archives of the Pathology Department of Helsinki University Central Hospital. Immunohistochemical staining of erbB2 was also performed among familial cases. RESULTS: BRCA1-associated cancers were diagnosed younger and were more ER-negative and PgR-negative, p53-positive and of higher grade than the other tumours. However, in multivariate analysis the independent factors compared with non-BRCA1/2 tumours were age, grade and PgR negativity. BRCA2 cases did not have such distinctive features compared with non-BRCA1/2 tumours or with unselected control tumours. Familial cases without BRCA1/2 mutations had tumours of lower grade than the other groups. CONCLUSIONS: BRCA1 families differed from mutation-negative families by age, grade and PgR status, whereas ER status was not an independent marker

Volumetric modulated arc therapy for synchronous bilateral whole breast irradiation – A case study

PurposeThe treatment planning of bilateral breast irradiation (BBI) is a challenging task. The overlapping of tangential fields is usually unavoidable without compromising the target coverage. The purpose of this study was to investigate the technical feasibility and benefits of a single isocentre volumetric modulated arc therapy (VMAT) in BBI.Methods and materialsTwo women with bilateral breast cancer were included in this case study. The first patient (Pat#1) underwent a bilateral breast-conserving surgery and sentinel lymph node biopsy. The second patient (Pat#2) underwent a bilateral ablation and axillary lymph node dissection. Planning target volumes (PTV) and organs at risk were delineated on CT images. VMAT plans were created with four (two for both sides, Pat#1) or two (one for each breast, Pat#2) separate VMAT fields. Subsequently, traditional tangential field plans were generated for each patient and the dosimetric parameters were compared.ResultsThe treatment times of the patients with VMAT were less than 15[[ce:hsp sp="0.25"/]]min with daily CBCT imaging. When compared to the standard tangential field technique, the VMAT plans improved the PTV dose coverage and dose homogeneity with improved sparing of lungs and heart. With traditional field arrangement, the overlapping of the tangential fields was inevitable without significantly compromising the target coverage, whereas with VMAT the hotspots were avoided. The patients were treated with the VMAT technique and no acute skin toxicity was observed with either of the patients.ConclusionsA single isocentre VMAT technique has been implemented clinically for BBI. With the VMAT techniques, the dose delivery was quick and the hotspots in the field overlapping areas were avoided. The PTV dose coverage was superior in VMAT plans when compared with conventional tangential technique plans

Clever-1 positive macrophages in breast cancer

Purpose: Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically, how Clever-1 + macrophages correlate with clinicopathologic factors, Tumor Infiltrating Lymphocytes (TILs) and prognosis. Methods: Tissue microarray blocks were made from 373 primary breast cancer operation specimens. Hematoxylin and Eosin (H&E-staining) and immunohistochemical staining with Clever-1, CD3, CD4 and CD8 antibodies were performed. Differences in quantities of Clever-1 + macrophages and TILs were analyzed. Clever-1 + cell numbers were correlated with 25-year follow-up survival data and with breast cancer clinicopathologic parameters. Results: Low numbers of intratumoral Clever-1 + cells were found to be an independent adverse prognostic sign. Increased numbers of Clever-1 + cells were found in high grade tumors and hormone receptor negative tumors. Tumors that had higher amounts of Clever-1 + cells also tended to have higher amounts of TILs. Conclusion: The association of intratumoral Clever-1 + macrophages with better prognosis might stem from the function of Clever as a scavenger receptor that modulates tumor stroma. The association of Clever-1 + macrophages with high number of TILs and better prognosis indicates that immunosuppression by M2 macrophages is not necessarily dampening adaptive immune responses but instead keeping them in control to avoid excess inflammation.</p