Measurements and Variability of Arterial Blood Pressure and Heart Interval in Conscious and Anesthetized Dogs

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Treatment response of colorectal cancer liver metastases to neoadjuvant or conversion therapy : a prospective multicentre follow-up study using MRI, diffusion-weighted imaging and H-1-MR spectroscopy compared with histology (subgroup in the RAXO trial)

Background: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. Patients and methods: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusionweighted imaging and H-1-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and KaplaneMeier estimates of overall survival (OS). Results: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). H-1-MRS revealed steatohepatosis induced by systemic therapy. Conclusions: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.Peer reviewe

Continuous mHealth Patch Monitoring for the Algorithm-Based Detection of Atrial Fibrillation: Feasibility and Diagnostic Accuracy Study

Peer reviewe

Continuous 24-h Photoplethysmogram Monitoring Enables Detection of Atrial Fibrillation

Aim: Atrial fibrillation (AF) detection is challenging because it is often asymptomatic and paroxysmal. We evaluated continuous photoplethysmogram (PPG) for signal quality and detection of AF.Methods: PPGs were recorded using a wrist-band device in 173 patients (76 AF, 97 sinus rhythm, SR) for 24 h. Simultaneously recorded 3-lead ambulatory ECG served as control. The recordings were split into 10-, 20-, 30-, and 60-min time-frames. The sensitivity, specificity, and F1-score of AF detection were evaluated for each time-frame. AF alarms were generated to simulate continuous AF monitoring. Sensitivities, specificities, and positive predictive values (PPVs) of the alarms were evaluated. User experiences of PPG and ECG recordings were assessed. The study was registered in the Clinical Trials database (NCT03507335).Results: The quality of PPG signal was better during night-time than in daytime (67.3 +/- 22.4% vs. 30.5 +/- 19.4%, p < 0.001). The 30-min time-frame yielded the highest F1-score (0.9536), identifying AF correctly in 72/76 AF patients (sensitivity 94.7%), only 3/97 SR patients receiving a false AF diagnosis (specificity 96.9%). The sensitivity and PPV of the simulated AF alarms were 78.2 and 97.2% at night, and 49.3 and 97.0% during the daytime. 82% of patients were willing to use the device at home.Conclusion: PPG wrist-band provided reliable AF identification both during daytime and night-time. The PPG data's quality was better at night. The positive user experience suggests that wearable PPG devices could be feasible for continuous rhythm monitoring.Peer reviewe

The Development of Mouse APECED Models Provides New Insight into the Role of AIRE in Immune Regulation

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy is a rare recessive autoimmune disorder caused by a defect in a single gene called AIRE (autoimmune regulator). Characteristics of this disease include a variable combination of autoimmune endocrine tissue destruction, mucocutaneous candidiasis and ectodermal dystrophies. The development of Aire-knockout mice has provided an invaluable model for the study of this disease. The aim of this review is to briefly highlight the strides made in APECED research using these transgenic murine models, with a focus on known roles of Aire in autoimmunity. The findings thus far are compelling and prompt additional areas of study which are discussed

Tulosperusteiset rahoitusmallit kalastonhoidon vauhdittajina

Ympäristöhaasteiden ratkaiseminen vaatii systeemisiä muutoksia ja rahallisia panostuksia. Samaan aikaan julkisen sektorin kyvykkyys rahoittaa vaadittavia toimenpiteitä on heikentynyt julkisen talouden kasvavan kestävyysvajeen vuoksi. On tärkeää kehittää aktiivisesti uusia rahoitustapoja, jotka tehostavat julkisen rahan vaikuttavuutta sekä perustuvat malleihin, joilla yksityistä sijoituspääomaa pystytään hyödyntämään ympäristötavoitteiden edistämisessä nykyistä enemmän. Uudet tulosperusteiset rahoitusmallit siirtävät tarkastelun tarkkaan rajattujen suoritteiden tai toimien hankinnasta tulosten ja vaikutusten perusteella tapahtuviin maksuihin ja muuttavat nykyiset ympäristöhaasteet sijoituskohteiksi. Kalavarojen tilan parantaminen on tärkeä yhteiskunnallinen tavoite, jonka saavuttaminen edellyttää onnistumisia mm. kalastuksen säätelyssä, vaellusreittien avaamisessa ja veden tilan parantamisessa. Esiselvityksessä tarkastellaan minkälaisiin tavoitteisiin ja toimenpiteisiin tulosperusteiset rahoitus- ja hankintamallit voisivat soveltua kalavarojen tilaa parantavien toimien osalta. Lisäksi työssä arvioidaan uudenlaisten rahastomallien mahdollisuuksia lisätä yksityistä rahoitusta tai sijoituspääomaa kalataloudellisten kunnostusten toteuttamiseen. Selvitystyön perusteella tavoitteena on käynnistää pilotointityö tulosperusteisista rahoitusmalleista kalataloudellisissa kunnostuksissa

Continuation of fluoropyrimidine treatment with S-1 after cardiotoxicity on capecitabine- or 5-fluorouracil-based therapy in patients with solid tumours : a multicentre retrospective observational cohort study

Publisher Copyright: © 2022 The Author(s)Background: Capecitabine- or 5-fluorouracil (5-FU)-based chemotherapy is widely used in many solid tumours, but is associated with cardiotoxicity. S-1 is a fluoropyrimidine with low rates of cardiotoxicity, but evidence regarding the safety of switching to S-1 after 5-FU- or capecitabine-associated cardiotoxicity is scarce. Patients and methods: This retrospective study (NCT04260269) was conducted at 13 centres in 6 countries. The primary endpoint was recurrence of cardiotoxicity after switch to S-1-based treatment due to 5-FU- or capecitabine-related cardiotoxicity: clinically meaningful if the upper boundary of the 95% confidence interval (CI; by competing risk) is not including 15%. Secondary endpoints included cardiac risk factors, diagnostic work-up, treatments, outcomes, and timelines of cardiotoxicity. Results: Per protocol, 200 patients, treated between 2011 and 2020 [median age 66 years (range 19-86); 118 (59%) males], were included. Treatment intent was curative in 145 (73%). Initial cardiotoxicity was due to capecitabine (n = 170), continuous infusion 5-FU (n = 22), or bolus 5-FU (n = 8), which was administered in combination with other chemotherapy, targeted agents, or radiotherapy in 133 patients. Previous cardiovascular comorbidities were present in 99 (50%) patients. Cardiotoxic events (n = 228/200) included chest pain (n = 125), coronary syndrome/infarction (n = 69), arrhythmia (n = 22), heart failure/cardiomyopathy (n = 7), cardiac arrest (n = 4), and malignant hypertension (n = 1). Cardiotoxicity was severe or life-threatening in 112 (56%) patients and led to permanent capecitabine/5-FU discontinuation in 192 (96%). After switch to S-1, recurrent cardiotoxicity was observed in eight (4%) patients (95% CI 2.02-7.89, primary endpoint met). Events were limited to grade 1-2 and occurred at a median of 16 days (interquartile range 7-67) from therapy switch. Baseline ischemic heart disease was a risk factor for recurrent cardiotoxicity (odds ratio 6.18, 95% CI 1.36-28.11). Conclusion: Switching to S-1-based therapy is safe and feasible after development of cardiotoxicity on 5-FU- or capecitabine-based therapy and allows patients to continue their pivotal fluoropyrimidine-based treatment.Peer reviewe

Centralized repeated resectability assessment of patients with colorectalliver metastases during first-line treatment : prospective study

Y Background: Metastasectomy is probably underused in metastatic colorectal cancer. The aim of this study was to investigate the effect of centralized repeated assessment on resectability rate of liver metastases. Methods: The prospective RAXO study was a nationwide study in Finland. Patients with treatable metastatic colorectal cancer at any site were eligible. This planned substudy included patients with baseline liver metastases between 2012 and 2018. Resectability was reassessed by the multidisciplinary team at Helsinki tertiary referral centre upfront and twice during first-line systemic therapy. Outcomes were resectability rates, management changes, and survival. Results: Of 812 patients included, 301 (37.1 per cent) had liver-only metastases. Of these, tumours were categorized as upfront resectable in 161 (53.5 per cent), and became amenable to surgery during systemic treatment in 63 (20.9 per cent). Some 207 patients (68.7 per cent) eventually underwent liver resection or ablation. At baseline, a discrepancy in resectability between central and local judgement was noted for 102 patients (33.9 per cent). Median disease-free survival (DFS) after first resection was 20 months and overall survival (OS) 79 months. Median OS after diagnosis of metastatic colorectal cancer was 80, 32, and 21 months in R0-1 resection, R2/ablation, and non-resected groups, and 5-year OS rates were 68, 37, and 9 per cent, respectively. Liver and extrahepatic metastases were present in 511 patients. Of these, tumours in 72 patients (14.1 per cent) were categorized as upfront resectable, and 53 patients (10.4 per cent) became eligible for surgery. Eventually 110 patients (21.5 per cent) underwent liver resection or ablation. At baseline, a discrepancy between local and central resectability was noted for 116 patients (22.7 per cent). Median DFS from first resection was 7 months and median OS 55 months. Median OS after diagnosis of metastatic colorectal cancer was 79, 42, and 17 months in R0-1 resection, R2/ablation, and non-resected groups, with 5-year OS rates of 65, 39, and 2 per cent, respectively. Conclusion: Repeated centralized resectability assessment in patients with colorectal liver metastases improved resection and survival rates.Peer reviewe

Syrjäytymisvaarassa olevien vajaakuntoisten nuorten kuntoutustarpeen arviointi

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