Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

Immune cell profiles of metastatic HER2-positive breast cancer patients according to the sites of metastasis

Purpose Recent works have characterized that metastatic site can affect the tumour immune profiles and efficiency of cancer immunotherapies. The prognosis of HER2-positive breast cancer is associated with the characteristics of the tumour immune microenvironment, with immunological cells playing a central role in efficiency of HER2-targeted antibodies. Here we investigated the prognostic significance of different metastatic sites and their correlation to tumour immune profiles in HER2-positive breast cancer treated with trastuzumab. Methods We collected all (n = 54) HER2-positive metastatic breast cancer patients treated with trastuzumab containing regimens at Oulu University Hospital 2009-2014. Pathological and clinical data were collected from electronic patient records. The tumour immune profiles were analysed from pre-treatment primary tumours using well-characterized immunological markers with computer-assisted immune cell counting. Results Of the metastatic sites, only liver metastases were associated with poor prognosis (hazard ratio 1.809, 95% confidence interval 1.004-3.262), especially when presented as the primary site of metastases. Of the other sites, pulmonary metastases characterized a patient profile with trend to improved survival. Of the studied tumour immunological markers, patients with liver metastases had low densities of CD3(+) T cells (p = 0.030) and M1-like macrophages in their primary tumours (p = 0.025). Of the other studied markers and sites, patients with pulmonary metastases had low STAB1(+)-immunosuppressive macrophage density in their primary tumours. Conclusion Our results suggest that the site of metastasis is associated with prognosis in HER2-positive breast cancer, highlighted by the poor prognosis of liver metastases. Furthermore, liver metastases were associated with adverse tumour immune cell profiles.Peer reviewe

Prognostic significance of spatial and density analysis of T lymphocytes in colorectal cancer

Background Although high T cell density is a strong favourable prognostic factor in colorectal cancer, the significance of the spatial distribution of T cells is incompletely understood. We aimed to evaluate the prognostic significance of tumour cell-T cell co-localisation and T cell densities. Methods We analysed CD3 and CD8 immunohistochemistry in a study cohort of 983 colorectal cancer patients and a validation cohort (N = 246). Individual immune and tumour cells were identified to calculate T cell densities (to derive T cell density score) and G-cross function values, estimating the likelihood of tumour cells being co-located with T cells within 20 mu m radius (to derive T cell proximity score). Results High T cell proximity score associated with longer cancer-specific survival in both the study cohort [adjusted HR for high (vs. low) 0.33, 95% CI 0.20-0.52, P-trend < 0.0001] and the validation cohort [adjusted HR for high (vs. low) 0.15, 95% CI 0.05-0.45, P-trend < 0.0001] and its prognostic value was independent of T cell density score. Conclusions The spatial point pattern analysis of tumour cell-T cell co-localisation could provide detailed information on colorectal cancer prognosis, supporting the value of spatial measurement of T cell infiltrates as a novel, robust tumour-immune biomarker.Peer reviewe

Immediate effects of deep brain stimulation of anterior thalamic nuclei on executive functions and emotion-attention interaction in humans

BACKGROUND: Deep brain stimulation (DBS) of anterior thalamic nuclei (ANT) is a novel promising therapeutic method for treating refractory epilepsy. Despite reports of subjective memory impairments and mood disturbances in patients with ANT-DBS, little is known of its effects on cognitive and affective processes. HYPOTHESIS: The anterior thalamus has connections to prefrontal and limbic networks important for cognitive control and emotional reactivity. More specifically, anterior cingulate cortex (ACC), linked with ANT, has been assigned roles related to response inhibition and attention allocation to threat. Thus, we hypothesized ANT-DBS to influence executive functions, particularly response inhibition, and modulate emotional reactivity to threat. METHOD: Twelve patients having undergone ANT-DBS for intractable epilepsy participated in the study. Patients performed a computer-based executive reaction time (RT) test—that is, a go/ no-go visual discrimination task with threat-related emotional distractors and rule switching, while the DBS was switched ON (5/5 mA constant current) and OFF every few minutes. RESULTS: ANT-DBS increased the amount of commission errors—that is, errors where subjects failed to withhold from responding. Furthermore, ANT-DBS slowed RTs in context of threat-related distractors. When stimulation was turned off, threat-related distractors had no distinct effect on RTs. CONCLUSION: We found immediate objective effects of ANT-DBS on human cognitive control and emotion-attention interaction. We suggest that ANT-DBS compromised response inhibition and enhanced attention allocation to threat due to altered functioning of neural networks that involve the DBS-target, ANT, and the regions connected to it such as ACC. The results highlight the need to consider affective and cognitive side-effects in addition to the therapeutic effect when adjusting stimulation parameters. Furthermore, this study introduces a novel window into cognitive and affective processes by modulating the associative and limbic networks with direct stimulation of key nodes in the thalamus

Early recovery of frontal EEG slow wave activity during propofol sedation predicts outcome after cardiac arrest

Aim of the study: EEG slow wave activity (SWA) has shown prognostic potential in post-resuscitation care. In this prospective study, we investigated the accuracy of continuously measured early SWA for prediction of the outcome in comatose cardiac arrest (CA) survivors. Methods: We recorded EEG with a disposable self-adhesive frontal electrode and wireless device continuously starting from ICU admission until 48 h from return of spontaneous circulation (ROSC) in comatose CA survivors sedated with propofol. We determined SWA by offline calculation of C-Trend (R) Index describing SWA as a score ranging from 0 to 100. The functional outcome was defined based on Cerebral Performance Category (CPC) at 6 months after the CA to either good (CPC 1-2) or poor (CPC 3-5). Results: Outcome at six months was good in 67 of the 93 patients. During the first 12 h after ROSC, the median C-Trend Index value was 38.8 (interquartile range 28.0-56.1) in patients with good outcome and 6.49 (3.01-18.2) in those with poor outcome showing significant difference (p < 0.001) at every hour between the groups. The index values of the first 12h predicted poor outcome with an area under curve of 0.86 (95% CI0.61-0.99). With a cutoff value of 20, the sensitivity was 83.3% (69.6%-92.3%) and specificity 94.7% (83.4%-99.7%) for categorization of outcome. Conclusion: EEG SWA measured with C-Trend Index during propofol sedation offers a promising practical approach for early bedside evaluation of recovery of brain function and prediction of outcome after CA.Peer reviewe

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Oulun seudun, Pohjois-Pohjanmaan ja Kainuun liikenteenhallintasuunnitelma

Oulun seudun, Pohjois-Pohjanmaan ja Kainuun liikenteenhallintasuunnitelmassa on esitetty keskeiset liikenteenhallinnan lähtökohdat, tavoitteet, kehittämistoimenpiteet, niiden kustannukset ja vaikutukset sekä aikatauluehdotus niiden toteutuksesta. Aktiivisessa liikenneverkon operoinnissa Oulun seudulla tähdätään erityisesti ajantasaiseen liikenteen ohjauksen ja tiedotuksen kehittämiseen sekä häiriönhallinnan parantamiseen ja liikenneverkon käytön optimointiin. Muilla kaupunkiseuduilla toimenpiteet kohdistuvat suurelta osin pistemäisten ongelmien ratkaisemiseen. Pääteillä aktiivinen liikenneverkon operointi kohdistuu tiekohtaisten liikenteenhallintajärjestelmien, häiriönhallinnan toimintamallien ja varareittijärjestelmien sekä tiekohtaisten ja seudullisten liikenteen ohjauksien kehittämiseen. Turvalliseen liikkumiseen tähtääviä liikenteenhallinnan toimenpiteitä ovat liikennevalojärjestelmien kehittäminen, häiriönhal linnan kehittäminen sekä nopeusrajoitusten noudattamista tukevat toimenpiteet. Liikenneturvallisuutta parannetaan myös pienillä liikenteenhallinnan turvallisuustoimenpiteillä, kuten liikuteltavat nopeusnäytöt, huomiovalot suojateillä esim. koulujen kohdilla ja liikennevalojen erityisohjaukset (esim. lasten pitkä vihreä). Joukkoliikenteen, kävelyn ja pyöräilyn toimenpiteet kohdistuvat pääosin Oulun seudulle. Toimenpiteitä ovat informaation määrän, laadun ja ajantasaisuuden parantaminen sekä valoetuuksien kehittäminen. Toimenpiteillä pyritään vaikuttamaan joukkoliikenteen kulkumuotoosuuden kasvuun lisäämällä sen houkuttelevuutta. Kevyen liikenteen kulkumuoto-osuuden kasvua tuetaan toteuttamalla kevyen liikenteen reittiopas ja kunnossapitotietopalveluja. Liikennejärjestelmän ajantasainen tilannekuva toimii liikenteenhallinnan toimintojen perustana. Oulun seudulla kehitetään liikenteen seurantaa ja ajantasaista liikennemallia, jonka avulla voidaan paremmin tiedottaa ja ohjata liikennettä sekä vaikuttaa liikenteen kysynnän ohjaukseen. Merkittävimpiä toimenpiteitä ovat liikenteenhallinnan tietoliikenneverkon rakentaminen ja liikennekameraverkon laajentaminen. Tilannekuvan kehittämisessä on tärkeää viranomaisten välisen yhteistyön syventäminen. Liikenteenhallinnan toimenpiteiden kokonaiskustannuksiksi v. 2012–2020 on arvioitu noin 17 milj. euroa ja ylläpitokustannusten suuruudeksi noin 1,5 milj. euroa vuodessa. Toimenpiteiden toteutuksen ajankohtaan vaikuttaa hyvin paljon vallitseva rahoitustilanne ja mahdolliset toimintaympäristön muutokset

Kaakkois-Suomen liikenteen hallinnan ydinsuunnitelma

Kaakkois-Suomen ELY-keskuksen liikenteen hallinnan ydinsuunnitelmassa on kuvattu liikenteen hallinnan palvelut ja päätoimenpiteet seuraavien vuosien aikana. Suunnitelmassa on esitetty myös alueen muiden toimijoiden sekä valtakunnallisten sidosryhmien liikenteen hallinnan lähivuosien tarpeita. Esitetyt toimenpiteet vaativat usein yhteistyötä eri toimijoiden kesken, minkä vuoksi vuorovaikutus ja yhteydenpito ohjelman toteuttamiseksi Kaakkois-Suomen alueella sekä kansallisesti on tärkeää. Erityisesti tällaisia osa‐alueita ovat häiriönhallinnan ja rajaliikenteen kehittäminen