Lactate-Induced Glucose Output Is Unchanged by Metformin at a Therapeutic Concentration - A Mass Spectrometry Imaging Study of the Perfused Rat Liver

Metformin is the first line drug for type 2 diabetes but its molecular mechanisms remain unclear. Here, we have studied the acute effect of a therapeutically relevant intrahepatic concentration of metformin on glucose production from lactate. We selected the perfused rat liver as experimental system since it enables the complete control of drug dosage. We used MALDI (matrix-assisted laser desorption/ionization) mass spectrometry imaging to estimate the concentration of metformin in the livers and we measured the concentration of glucose in the effluent medium under basal conditions and following lactate addition. MALDI mass spectra of thin-sections of freeze-clamped rat liver perfused with metformin showed a peak at 130.16 m/z which was unambiguously assigned to metformin. The mass spectrometric detection limit was at a tissue concentration of about 250 nM, and uptake of metformin from the perfusion medium to the liver occurred with a K-m of 0.44 mM. Metformin was evenly distributed in the liver irrespective of its concentration in the perfusion medium and the duration of a perfusion. At a parenchymal concentration of 30 mu M, metformin did not induce any significant suppression of the basal or lactate-induced glucose release from the liver. These results show that matrix-assisted laser desorption/ionization mass spectrometry imaging can be applied to estimate the tissue concentration and distribution of metformin in a therapeutically relevant micromolar concentration range. Our findings challenge the view that metformin causes an inhibition of glucose release from the liver by an acute inhibition of mitochondrial glycerol 3-phosphate dehydrogenase (EC 1.1.5.3).Peer reviewe

Data on association between QRS duration on prehospital ECG and mortality in patients with confirmed STEMI

Data presented in this article relates to the research article entitled âAssociation between QRS duration on prehospital ECG and mortality in patients with suspected STEMIâ (Hansen et al., in press) [1].Data on the prognostic effect of automatically recoded QRS duration on prehospital ECG and presence of classic left and right bundle branch block in 1777 consecutive patients with confirmed ST segment elevation AMI is presented. Multivariable analysis, suggested that QRS duration >111 ms, left bundle branch block and right bundle branch block were independent predictors of 30 days all-cause mortality. For interpretation and discussion of these data, refer to the research article referenced above

Mortality risk prediction in elderly patients with cardiogenic shock : results from the CardShock study

Aims This study aimed to assess the utility of contemporary clinical risk scores and explore the ability of two biomarkers [growth differentiation factor-15 (GDF-15) and soluble ST2 (sST2)] to improve risk prediction in elderly patients with cardiogenic shock. Methods and results Patients (n = 219) from the multicentre CardShock study were grouped according to age (elderly >= 75 years and younger). Characteristics, management, and outcome between the groups were compared. The ability of the CardShock risk score and the IABP-SHOCK II score to predict in-hospital mortality and the additional value of GDF-15 and sST2 to improve risk prediction in the elderly was evaluated. The elderly constituted 26% of the patients (n = 56), with a higher proportion of women (41% vs. 21%, P <0.05) and more co-morbidities compared with the younger. The primary aetiology of shock in the elderly was acute coronary syndrome (84%), with high rates of percutaneous coronary intervention (87%). Compared with the younger, the elderly had higher in-hospital mortality (46% vs. 33%; P = 0.08), but 1 year post-discharge survival was excellent in both age groups (90% in the elderly vs. 88% in the younger). In the elderly, the risk prediction models demonstrated an area under the curve of 0.75 for the CardShock risk score and 0.71 for the IABP-SHOCK II score. Incorporating GDF-15 and sST2 improved discrimination for both risk scores with areas under the curve ranging from 0.78 to 0.84. Conclusions Elderly patients with cardiogenic shock have higher in-hospital mortality compared with the younger, but post-discharge outcomes are similar. Contemporary risk scores proved useful for early mortality risk prediction also in the elderly, and risk stratification could be further improved with biomarkers such as GDF-15 or sST2.Peer reviewe

Adrenomedullin : a marker of impaired hemodynamics, organ dysfunction, and poor prognosis in cardiogenic shock

Background: The clinical CardShock risk score, including baseline lactate levels, was recently shown to facilitate risk stratification in patients with cardiogenic shock (CS). As based on baseline parameters, however, it may not reflect the change in mortality risk in response to initial therapies. Adrenomedullin is a prognostic biomarker in several cardiovascular diseases and was recently shown to associate with hemodynamic instability in patients with septic shock. The aim of our study was to evaluate the prognostic value and association with hemodynamic parameters of bioactive adrenomedullin (bio-ADM) in patients with CS. Methods: CardShock was a prospective, observational, European multinational cohort study of CS. In this sub-analysis, serial plasma bio-ADM and arterial blood lactate measurements were collected from 178 patients during the first 10 days after detection of CS. Results: Both bio-ADM and lactate were higher in 90-day non-survivors compared to survivors at all time points (P <0.05 for all). Lactate showed good prognostic value during the initial 24 h (AUC 0.78 at admission and 0.76 at 24 h). Subsequently, lactate returned normal ( 55.7 pg/mL) at 48 h compared to those with low bio-ADM levels (49.1 vs. 22.6%, P = 0.001). High levels of bio-ADM were associated with impaired cardiac index, mean arterial pressure, central venous pressure, and systolic pulmonary artery pressure during the study period. Furthermore, high levels of bio-ADM at 48 to 96 h were related to persistently impaired cardiac and end-organ function. Conclusions: Bio-ADM is a valuable prognosticator and marker of impaired hemodynamics in CS patients. High levels of bio-ADM may show shock refractoriness and developing end-organ dysfunction and thus help to guide therapeutic approach in patients with CS.Peer reviewe

Use of noninvasive and invasive mechanical ventilation in cardiogenic shock : A prospective multicenter study

Background: Despite scarce data, invasive mechanical ventilation (MV) is widely recommended over noninvasive ventilation (NIV) for ventilatory support in cardiogenic shock (CS). We assessed the real-life use of different ventilation strategies in CS and their influence on outcome focusing on the use of NIV and MV. Methods: 219 CS patients were categorized by the maximum intensity of ventilatory support they needed during the first 24 h into MV (n= 137; 63%), NIV(n= 26; 12%), and supplementary oxygen (n= 56; 26%) groups. We compared the clinical characteristics and 90-day outcome between the MV and the NIV groups. Results: Mean age was 67 years, 74% were men. The MV and NIV groups did not differ in age, medical history, etiology of CS, PaO2/FiO(2) ratio, baseline hemodynamics or LVEF. MV patients predominantly presented with hypoperfusion, with more severe metabolic acidosis, higher lactate levels and greater need for vasoactive drugs, whereas NIV patients tended to be more often congestive. 90-day outcome was significantly worse in the MV group (50% vs. 27%), but after propensity score adjustment, mortality was equal in both groups. Confusion, prior CABG, ACS etiology, higher lactate level, and lower baseline PaO2 were independent predictors of mortality, where as ventilation strategy did not have any influence on outcome. Conclusions: Although MV is generally recommended mode of ventilatory support in CS, a fair number of patients were successfully treated with NIV. Moreover, ventilation strategy was not associated with outcome. Thus, NIV seems a safe option for properly chosen CS patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Myocardial Work in Patients Hospitalized With COVID‐19:Relation to Biomarkers, COVID‐19 Severity, and All‐Cause Mortality

BACKGROUND: COVID‐19 infection has been hypothesized to affect left ventricular function; however, the underlying mechanisms and the association to clinical outcome are not understood. The global work index (GWI) is a novel echocardiographic measure of systolic function that may offer insights on cardiac dysfunction in COVID‐19. We hypothesized that GWI was associated with disease severity and all‐cause death in patients with COVID‐19. METHODS AND RESULTS: In a multicenter study of patients admitted with COVID‐19 (n=305), 249 underwent pressure‐strain loop analyses to quantify GWI at a median time of 4 days after admission. We examined the association of GWI to cardiac biomarkers (troponin and NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide]), disease severity (oxygen requirement and CRP [C‐reactive protein]), and all‐cause death. Patients with elevated troponin (n=71) exhibited significantly reduced GWI (1508 versus 1707 mm Hg%; P=0.018). A curvilinear association to NT‐proBNP was observed, with increasing NT‐proBNP once GWI decreased below 1446 mm Hg%. Moreover, GWI was significantly associated with a higher oxygen requirement (relative increase of 6% per 100–mm Hg% decrease). No association was observed with CRP. Of the 249 patients, 37 died during follow‐up (median, 58 days). In multivariable Cox regression, GWI was associated with all‐cause death (hazard ratio, 1.08 [95% CI, 1.01–1.15], per 100–mm Hg% decrease), but did not increase C‐statistics when added to clinical parameters. CONCLUSIONS: In patients admitted with COVID‐19, our findings indicate that NT‐proBNP and troponin may be associated with lower GWI, whereas CRP is not. GWI was independently associated with all‐cause death, but did not provide prognostic information beyond readily available clinical parameters. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04377035

Haavainen paksusuolitulehdus : tietopaketti Terveysnettiin

Tämän projektin tehtävänä oli tuottaa tietopaketti haavaisesta paksusuolitulehduksesta Terveysnetti- verkkosivustolle. Terveysnetti on Turun ammattikorkeakoulun, Salon terveyskeskuksen, Salon aluesairaalan ja Salon kaupungin ylläpitämä verkkosivusto. Verkkosivusto on jaettu eri-ikäisille suunnattuihin osa-alueisiin, joita ovat juniorinetti, nuorisonetti, työikäisten netti ja seniorinetti. Tämän opinnäytetyön sisältö rajattiin koskemaan työikäisten nettiin kuuluvaa sisältöä. Tavoitteena oli tehdä helposti omaksuttava ja helppolukuinen tietopaketti äskettäin diagnoosin saaneille ja heidän läheisilleen. Projektin tuotoksena syntyi haavaista paksusuolitulehdusta käsittelevä verkkosivusto. Verkkosivusto jaettiin seuraaviin osa-alueisiin: tietoa haavaisesta paksusuolitulehduksesta, oireet, tutkimukset, hoito, elämä haavaisen paksusuolitulehduksen kanssa, liitännäissairaudet ja linkkejä. Haavainen paksusuolitulehdus on krooninen tulehduksellinen suolistosairaus, jonka tarkkaa syntymekanismia ei tunneta. Haavaista paksusuolitulehdusta pidetään tyypillisesti nuorten aikuisten sairautena, sillä tavanomainen sairastumisikä on 20 – 35 ikävuoden välillä. Haavaisen paksusuolitulehduksen esiintyvyys ja ilmaantuvuus on ollut parin viimeisen vuosikymmenen aikana kasvussa. Esiintyvyydeksi arvioidaan 300 - 400 / 100 000 henkilöä. Taudinkulku vaihtelee yksilöllisesti, oireettomien ja oireellisten pahenemisvaiheiden välillä. Suolitulehdus esiintyy vaihtelevan laajuisella alueella paksusuolessa. Oireina ovat tyypillisesti veriripuli, vatsakivut ja limaiset ulosteet. Haavaiseen paksusuolitulehdukseen saattaa liittyä myös eri elinjärjestelmissä ilmaantuvia liitännäissairauksia. Sairauteen ei ole toistaiseksi löydetty parantavaa hoitoa – ensisijaisena hoitona on lääkehoito. Lääkehoidosta huolimatta noin 30 % sairastuneista hoidetaan lopulta leikkauksella. Sairauden kroonisesta luonteesta huolimatta valtaosa sairastuneista elää pääosin normaalia elämää. Pahenemisvaiheen aikana ilmenevät oireet voivat haitata opiskelua, työntekoa ja harrastuksia.The purpose of this project was to create an information package about ulcerative colitis for the Terveysnetti website. Terveysnetti is maintained by the Turku University of Applied Sciences, the Salo healthcare center, and Salo regional hospital and the City of Salo. The website is divided into different parts for different age groups: junior net, youth net, working-age net and senior net. The scope of this final project was limited to the contents for the working-age net. The goal was to produce an information package, which is easy to read and understand, for people who have recently received a diagnosis, and their loved ones. Hence, the outcome of the project was a webpage related to the topic. The webpage was divided into the following components: information pertaining to ulcerative colitis, symptoms, examinations, treatment, living with ulcerative colitis, comorbid conditions and links. Ulcerative colitis is a chronic, inflammatory disease of the intestines for which the mechanism of the formation of the disease is unknown. Ulcerative colitis is typically considered an illness in young adults because people aged between 20 and 35 most commonly suffer from the disease. The occurrence and frequency of ulcerative colitis has been on the rise in the past couple of decades. The occurrence of the disease is estimated to be 300–400/100,000 people. The course of the disease varies between asymptomatic and symptomatic periods, depending on the individual. An infection occurs in varying dimensions in the large intestine. Typical symptoms are bloody diarrhea, stomach pains and mucous stools. Ulcerative colitis may also be associated with various comorbid conditions in various organs. There are no known cures for the disease at the moment; it is primarily treated with medication. Despite treatment with medication, about 30 % of those diagnosed with the disease are eventually operated on. Despites the disease’s chronic nature, the majority of those diagnosed with the disease live a normal life. The symptoms occurring during a relapse of the disease may impede the performance of study, work and hobbies

Is the high intensity symptoms experienced by patients admitted with chronic obstructive pulmonary disease documented by health professionals? - a prospective survey with comparison of patient reported outcomes and medical records

Context: Patients with chronic obstructive pulmonary disease (COPD) have a high symptom burden and reduced quality of life. There is an increasing attention on palliation for patients with COPD. Recognition of symptoms is a prerequisite for palliation. Objectives: We aim to investigate the extent to which symptoms in patients with COPD are recognized in the documentation of the health professionals, indicated in ‘Doctors Symptom Recognition Rate’ (DSR), ‘Nurses Symptom Recognition Rate’ (NSR) or ‘Doctors and/or Nurses Symptom Recognition rates ’(DNSR) as a team, respectively. Methods: Patients with COPD (n = 40) admitted in two respiratory units, responded within 48 h on two symptom-screening-tools that access quality of life; COPD assessment test (CAT) used for the treatment of COPD and EORTC-QLQ-C15-PAL used for palliation in patients with cancer. Patient-described symptomatology was compared to the symptoms as recognized in the documentation of doctors and/or nurses. Results: There was a significant discrepancy between the symptomatology indicated by patients with COPD on CAT and EORTC-QLQ-C15-PAL, and the degree by which it was recognized in the medical records indicated in DSR or NSR. In 30 out of 44 items DSR or NSR were < 70%. There was a significant difference between DNSR versus DSR or NSR, respectively, in 19 out of 22 items. Conclusion: A team-based symptom recognition DNSR is superior when compared to DSR or NSR. Team-based systematic screening is suggested as a pathway to increase symptom recognition in patients with COPD. Increased rates of symptom recognition may improve symptom alleviation and thus palliation