Browsing by Subject "INJURY"

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  • Sidorova, Yulia A.; Bespalov, Maxim M.; Wong, Agnes W.; Kambur, Oleg; Jokinen, Viljami; Lilius, Tuomas O.; Suleymanova, Ilida; Karelson, Gunnar; Rauhala, Pekka V.; Karelson, Mati; Osborne, Peregrine B.; Keast, Janet R.; Kalso, Eija A.; Saarma, Mart (2017)
    Neuropathic pain caused by nerve damage is a common and severe class of chronic pain. Disease-modifying clinical therapies are needed as current treatments typically provide only symptomatic relief; show varying clinical efficacy; and most have significant adverse effects. One approach is targeting either neurotrophic factors or their receptors that normalize sensory neuron function and stimulate regeneration after nerve damage. Two candidate targets are glial cell line-derived neurotrophic factor (GDNF) and artemin (ARTN), as these GDNF family ligands (GFLs) show efficacy in animal models of neuropathic pain (Boucher et al., 2000; Gardell et al., 2003: Wang et al., 2008, 2014). As these protein ligands have poor drug-like properties and are expensive to produce for clinical use, we screened 18,400 drug-like compounds to develop small molecules that act similarly to GFLs (GDNF mimetics). This screening identified BT13 as a compound that selectively targeted GFL receptor RET to activate downstream signaling cascades. BT13 was similar to NGF and ARTN in selectively promoting neurite outgrowth from the peptidergic class of adult sensory neurons in culture, but was opposite to ARTN in causing neurite elongation without affecting initiation. When administered after spinal nerve ligation in a rat model of neuropathic pain, 20 and 25 mg/kg of BT13 decreased mechanical hypersensitivity and normalized expression of sensory neuron markers in dorsal root ganglia. In control rats, BT13 had no effect on baseline mechanical or thermal sensitivity, motor coordination, or weight gain. Thus, small molecule BT13 selectively activates RET and offers opportunities for developing novel disease-modifying medications to treat neuropathic pain.
  • Ala-Kurikka, Tommi; Pospelov, Alexey; Summanen, Milla; Alafuzoff, Aleksander; Kurki, Samu; Voipio, Juha; Kaila, Kai (2021)
    Objective Birth asphyxia (BA) is often associated with seizures that may exacerbate the ensuing hypoxic-ischemic encephalopathy. In rodent models of BA, exposure to hypoxia is used to evoke seizures, that commence already during the insult. This is in stark contrast to clinical BA, in which seizures are typically seen upon recovery. Here, we introduce a term-equivalent rat model of BA, in which seizures are triggered after exposure to asphyxia. Methods Postnatal day 11-12 male rat pups were exposed to steady asphyxia (15 min; air containing 5% O-2 + 20% CO2) or to intermittent asphyxia (30 min; three 5 + 5-min cycles of 9% and 5% O-2 at 20% CO2). Cortical activity and electrographic seizures were recorded in freely behaving animals. Simultaneous electrode measurements of intracortical pH, Po-2, and local field potentials (LFPs) were made under urethane anesthesia. Results Both protocols decreased blood pH to Significance The rate of brain pH recovery has a strong influence on post-asphyxia seizure propensity. The recurring hypoxic episodes during intermittent asphyxia promote neuronal excitability, which leads to seizures only after the suppressing effect of the hypercapnic acidosis is relieved. The present rodent model of BA is to our best knowledge the first one in which, consistent with clinical BA, behavioral and electrographic seizures are triggered after and not during the BA-mimicking insult.
  • Licht, Tamar; Kreisel, Tirzah; Biala, Yoav; Mohan, Sandesh; Yaari, Yoel; Anisimov, Andrey; Alitalo, Kari; Keshet, Eli (2020)
    Multiple insults to the brain lead to neuronal cell death, thus raising the question to what extent can lost neurons be replenished by adult neurogenesis. Here we focused on the hippocampus and especially the dentate gyrus (DG), a vulnerable brain region and one of the two sites where adult neuronal stem cells (NSCs) reside. While adult hippocampal neurogenesis was extensively studied with regard to its contribution to cognitive enhancement, we focused on their underestimated capability to repair a massively injured, nonfunctional DG. To address this issue, we inflicted substantial DG-specific damage in mice of either sex either by diphtheria toxin-based ablation of >50% of mature DG granule cells (GCs) or by prolonged brain-specific VEGF overexpression culminating in extensive, highly selective loss of DG GCs (thereby also reinforcing the notion of selective DG vulnerability). The neurogenic system promoted effective regeneration by increasing NSCs proliferation/survival rates, restoring a nearly original DG mass, promoting proper rewiring of regenerated neurons to their afferent and efferent partners, and regaining of lost spatial memory. Notably, concomitantly with the natural age-related decline in the levels of neurogenesis, the regenerative capacity of the hippocampus also subsided with age. The study thus revealed an unappreciated regenerative potential of the young DG and suggests hippocampal NSCs as a critical reservoir enabling recovery from catastrophic DG damage.
  • Hänninen, Mikko; Jäntti, Toni; Tolppanen, Heli; Segersvärd, Heli; Tarvasmäki, Tuukka; Lassus, Johan; Vausort, Melanie; Devaux, Yvan; Sionis, Alessandro; Tikkanen, Ilkka; Harjola, Veli-Pekka; Lakkisto, Päivi (2020)
    Cardiogenic shock (CS) is a life-threatening emergency. New biomarkers are needed in order to detect patients at greater risk of adverse outcome. Our aim was to assess the characteristics of miR-21-5p, miR-122-5p, and miR-320a-3p in CS and evaluate the value of their expression levels in risk prediction. Circulating levels of miR-21-5p, miR-122-5p, and miR-320a-3p were measured from serial plasma samples of 179 patients during the first 5-10 days after detection of CS, derived from the CardShock study. Acute coronary syndrome was the most common cause (80%) of CS. Baseline (0 h) levels of miR-21-5p, miR-122-5p, and miR-320a-3p were all significantly elevated in nonsurvivors compared to survivors (p <0.05 for all). Above median levels at 0h of each miRNA were each significantly associated with higher lactate and alanine aminotransferase levels and decreased glomerular filtration rates. After adjusting the multivariate regression analysis with established CS risk factors, miR-21-5p and miR-320a-3p levels above median at 0 h were independently associated with 90-day all-cause mortality (adjusted hazard ratio 1.8 (95% confidence interval 1.1-3.0), p = 0.018; adjusted hazard ratio 1.9 (95% confidence interval 1.2-3.2), p = 0.009, respectively). In conclusion, circulating plasma levels of miR-21-5p, miR-122-5p, and miR-320a-3p at baseline were all elevated in nonsurvivors of CS and associated with markers of hypoperfusion. Above median levels of miR-21-5p and miR-320a-3p at baseline appear to independently predict 90-day all-cause mortality. This indicates the potential of miRNAs as biomarkers for risk assessment in cardiogenic shock.
  • Kuula, Juho; Martola, Juha; Hakkarainen, Antti; Räikkönen, Katri; Savolainen, Sauli; Salli, Eero; Hovi, Petteri; Björkqvist, Johan; Kajantie, Eero; Lundbom, Nina (2022)
    Objectives To assess radiographic brain abnormalities and investigate volumetric differences in adults born preterm at very low birth weight ( Study design We recruited 79 adult same-sex sibling pairs with one born preterm at very low birth weight and the sibling at term. We acquired 3-T brain magnetic resonance imaging from 78 preterm participants and 72 siblings. A neuroradiologist, masked to participants' prematurity status, reviewed the images for parenchymal and structural abnormalities, and FreeSurfer software 6.0 was used to conduct volumetric analyses. Data were analyzed by linear mixed models. Results We found more structural abnormalities in very low birth weight participants than in siblings (37% vs 13%). The most common finding was periventricular leukomalacia, present in 15% of very low birth weight participants and in 3% of siblings. The very low birth weight group had smaller absolute brain volumes (-0.4 SD) and, after adjusting for estimated intracranial volume, less gray matter (-0.2 SD), larger ventricles (1.5 SD), smaller thalami (-0.6 SD), caudate nuclei (-0.4 SD), right hippocampus (-0.4 SD), and left pallidum (-0.3 SD). We saw no volume differences in total white matter (-0.04 SD; 95% CI, -0.13 to 0.09). Conclusions Preterm very low birth weight adults had a higher prevalence of brain abnormalities than their termborn siblings. They also had smaller absolute brain volumes, less gray but not white matter, and smaller volumes in several gray matter structures.
  • Goubert, Emmanuelle; Altvater, Marc; Rovira, Marie-Noelle; Khalilov, Ilgam; Mazzarino, Morgane; Sebastiani, Anne; Schaefer, Michael K. E.; Rivera, Claudio; Pellegrino, Christophe (2019)
    Brain trauma triggers a cascade of deleterious events leading to enhanced incidence of drug resistant epilepsies, depression, and cognitive dysfunctions. The underlying mechanisms leading to these alterations are poorly understood and treatment that attenuates those sequels are not available. Using controlled-cortical impact as an experimental model of brain trauma in adult mice, we found a strong suppressive effect of the sodium-potassium-chloride importer (NKCC1) specific antagonist bumetanide on the appearance of depressive-like behavior. We demonstrate that this alteration in behavior is associated with an impairment of post-traumatic secondary neurogenesis within the dentate gyrus of the hippocampus. The mechanism mediating the effect of bumetanide involves early transient changes in the expression of chloride regulatory proteins and qualitative changes in GABA(A) mediated transmission from hyperpolarizing to depolarizing after brain trauma. This work opens new perspectives in the early treatment of human post-traumatic induced depression. Our results strongly suggest that bumetanide might constitute an efficient prophylactic treatment to reduce neurological and psychiatric consequences of brain trauma.
  • Pham, Dan Duc; Bruelle, Celine; Do, Hai Thi; Pajanoja, Ceren; Jin, Congyu; Olkkonen, Vesa M.; Eriksson-Rosenberg, Ove; Jauhiainen, Matti; Lalowski, Maciej; Lindholm, Dan (2019)
    Lipid-induced toxicity is part of several human diseases, but the mechanisms involved are not fully understood. Fatty liver is characterized by the expression of different growth and tissue factors. The neurotrophin, nerve growth factor (NGF) and its pro-form, pro-NGF, are present in fatty liver together with p75 neurotrophin receptor (p75NTR). Stimulation of human Huh7 hepatocyte cells with NGF and pro-NGF induced Sterol-regulator-element-binding protein-2 (SREBP2) activation and increased Low-Density Lipoprotein Receptor (LDLR) expression. We observed that phosphorylation of caspase-2 by p38 MAPK was essential for this regulation involving a caspase-3-mediated cleavage of SREBP2. RNA sequencing showed that several genes involved in lipid metabolism were altered in p75NTR-deficient mouse liver. The same lipogenic genes were downregulated in p75NTR gene-engineered human Huh7 cells and reciprocally upregulated by stimulation of p75NTRs. In the knock-out mice the serum cholesterol and triglyceride levels were reduced, suggesting a physiological role of p75NTRs in whole-body lipid metabolism. Taken together, this study shows that p75NTR signaling influences a network of genes involved in lipid metabolism in liver and hepatocyte cells. Modulation of p75NTR signaling may be a target to consider in various metabolic disorders accompanied by increased lipid accumulation.
  • Kluger, Yoram; Ben Ishay, Ofir; Sartelli, Massimo; Katz, Amit; Ansaloni, Luca; Gomez, Carlos Augusto; Biffl, Walter; Catena, Fausto; Fraga, Gustavo P.; Di Saverio, Salomone; Goran, Augustin; Ghnnam, Wagih; Kashuk, Jeffry; Leppaniemi, Ari; Marwah, Sanjay; Moore, Ernest E.; Bala, Miklosh; Massalou, Damien; Mircea, Chirica; Bonavina, Luigi (2015)
    Caustic material ingestion injuries (CMI) are uncommon. Only 5,000 cases are reported in the United States each year and most acute care healthcare facilities admit only a few cases annually. Accordingly, no single institution can claim extensive experience, and management protocols are most probably based on either expert opinion or literature reports. In this study, we will attempt to review opinions and practices of representatives of the board members of the World Society of Emergency Surgery and compare them to the current literature.
  • Wibroe, Morten; Cappelen, Johan; Castor, Charlotte; Clausen, Niels; Grillner, Pernilla; Gudrunardottir, Thora; Gupta, Ramneek; Gustavsson, Bengt; Heyman, Mats; Holm, Stefan; Karppinen, Atte; Klausen, Camilla; Lönnqvist, Tuula; Mathiasen, Rene; Nilsson, Pelle; Nysom, Karsten; Persson, Karin; Rask, Olof; Schmiegelow, Kjeld; Sehested, Astrid; Thomassen, Harald; Tonning-Olsson, Ingrid; Zetterqvist, Barbara; Juhler, Marianne (2017)
    Background: Central nervous system tumours constitute 25% of all childhood cancers; more than half are located in the posterior fossa and surgery is usually part of therapy. One of the most disabling late effects of posterior fossa tumour surgery is the cerebellar mutism syndrome (CMS) which has been reported in up to 39% of the patients but the exact incidence is uncertain since milder cases may be unrecognized. Recovery is usually incomplete. Reported risk factors are tumour type, midline location and brainstem involvement, but the exact aetiology, surgical and other risk factors, the clinical course and strategies for prevention and treatment are yet to be determined. Methods: This observational, prospective, multicentre study will include 500 children with posterior fossa tumours. It opened late 2014 with participation from 20 Nordic and Baltic centres. From 2016, five British centres and four Dutch centres will join with a total annual accrual of 130 patients. Three other major European centres are invited to join from 2016/17. Follow-up will run for 12 months after inclusion of the last patient. All patients are treated according to local practice. Clinical data are collected through standardized online registration at pre-determined time points pre- and postoperatively. Neurological status and speech functions are examined pre- operatively and postoperatively at 1-4 weeks, 2 and 12 months. Pre- and postoperative speech samples are recorded and analysed. Imaging will be reviewed centrally. Pathology is classified according to the 2007 WHO system. Germline DNA will be collected from all patients for associations between CMS characteristics and host genome variants including pathway profiles. Discussion: Through prospective and detailed collection of information on 1) differences in incidence and clinical course of CMS for different patient and tumour characteristics, 2) standardized surgical data and their association with CMS, 3) diversities and results of other therapeutic interventions, and 4) the role of host genome variants, we aim to achieve a better understanding of risk factors for and the clinical course of CMS - with the ultimate goal of defining strategies for prevention and treatment of this severely disabling condition.
  • Lalowski, Maciej M.; Björk, Susann; Finckenberg, Piet; Soliymani, Rabah; Tarkia, Miikka; Calza, Giulio; Blokhina, Daria; Tulokas, Sari; Kankainen, Matti; Lakkisto, Päivi; Baumann, Marc; Kankuri, Esko; Mervaala, Eero (2018)
    The heart of a newborn mouse has an exceptional capacity to regenerate from myocardial injury that is lost within the first week of its life. In order to elucidate the molecular mechanisms taking place in the mouse heart during this critical period we applied an untargeted combinatory multiomics approach using large-scale mass spectrometry-based quantitative proteomics, metabolomics and mRNA sequencing on hearts from 1-day-old and 7-day-old mice. As a result, we quantified 1.937 proteins (366 differentially expressed), 612 metabolites (263 differentially regulated) and revealed 2.586 differentially expressed gene loci (2.175 annotated genes). The analyses pinpointed the fructose-induced glycolysis-pathway to be markedly active in 1-day-old neonatal mice. Integrated analysis of the data convincingly demonstrated cardiac metabolic reprogramming from glycolysis to oxidative phosphorylation in 7-days old mice, with increases of key enzymes and metabolites in fatty acid transport (acylcarnitines) and beta-oxidation. An upsurge in the formation of reactive oxygen species and an increase in oxidative stress markers, e.g., lipid peroxidation, altered sphingolipid and plasmalogen metabolism were also evident in 7-days mice. In vitro maintenance of physiological fetal hypoxic conditions retained the proliferative capacity of cardiomyocytes isolated from newborn mice hearts. In summary, we provide here a holistic, multiomics view toward early postnatal changes associated with loss of a tissue regenerative capacity in the neonatal mouse heart. These results may provide insight into mechanisms of human cardiac diseases associated with tissue regenerative incapacity at the molecular level, and offer a prospect to discovery of novel therapeutic targets.
  • Boström, Anna; Hielm-Bjorkman, Anna; Chang, Yu-Mei; Weller, Renate; Davies, Emma (2014)
  • Nummela, Mari T.; Pyhältö, Tuomo T.; Bensch, Frank V.; Heinänen, Mikko T.; Koskinen, Seppo K. (2022)
    Purpose To assess the healing of costal cartilage fractures (CCFX) in patients with blunt polytrauma with follow-up imaging and clinical examination. Effect on physical performance and quality of life (QoL) was also evaluated. Methods The study group comprised twenty-one patients with diagnosed CCFX in trauma CT. All the patients underwent MRI, ultrasound, ultra-low-dose CT examinations, and clinical status control. The patients completed QoL questionnaires. Two radiologists evaluated the images regarding fracture union, dislocation, calcifications, and persistent edema at fracture site. An attending trauma surgeon clinically examined the patients, with emphasis on focal tenderness and ribcage mobility. Trauma registry data were accessed to evaluate injury severity and outcome. Results The patients were imaged at an average of 34.1 months (median 36, range 15.8-57.7) after the initial trauma. In 15 patients (71.4%), CCFX were considered stable on imaging. Cartilage calcifications were seen on healed fracture sites in all the patients. The fracture dislocation had increased in 5 patients (23.8%), and 1 patient (4.8%) showed signs of a non-stable union. Four patients (19.0%) reported persistent symptoms from CCFX. Conclusion Non-union in CCFX is uncommon but may lead to decreased stability and discomfort. Both clinical and radiological examinations play an important part in the post-traumatic evaluation of CCFX. CT and MRI visualize the healing process, while dynamic ultrasound may reveal instability. No significant difference in QoL was detected between patients with radiologically healed and non-healed CCFX. Post-traumatic disability was mostly due to other non-thoracic injuries.
  • Hafez, Ahmad; Ibrahim, Tarik F.; Raj, Rahul; Antinheimo, Jussi; Siironen, Jari; Hernesniemi, Juha (2016)
    BACKGROUND: Most of the physician's attention during spinal surgery, when using wires and screws, is toward the avoidance of injuries of critical structures (nerves and vessels). When such wires are broken during surgery, the most important point is to take them out safely or, if it is impossible, to leaf them in secure place and follow the patient closely. Migrations of broken Kirschner wire (K-wire) are well known in literature; however, to the best of our knowledge, migration of a fractured K-wire during anterior atlantoaxial fixation of cervical spine has not been reported in the literature. CASE DESCRIPTION: We report a case in which a fractured K-wire was imbedded in the lateral mass of C1 for 3 years and then migrated to endanger the dominant right vertebral artery. By using posterior approach and drilling right part of posterior arch of C1, we manage to secure the vertebral artery. The broken K-wire was extracted successfully. In our case, with optimal follow-up, the burred wire inside hard bone was moved in delayed fashion to come out of the bone, grooving the dominant vertebral artery. CONCLUSIONS: Our recommendation is to inspect the K-wire before using it and to try retrieve as much as possible when removing it.
  • Rytkönen, Kaisa; Ventä, Irja (2018)
    The aim of the study was to evaluate the proximity of the mandibular third molar (M3) and the inferior alveolar canal (IAC) in a panoramic radiograph of 20-year-old subjects. The specific aim was to assess differences in this proximity over time. Two similar samples of panoramic radiographs taken in a routine oral health examination with 20-year time interval were examined retrospectively and images with both mandibular M3s were included. The material consisted of 300 subjects (25% men, mean age 20.5 +/- 0.6 years). The radiographic relationship between the mandibular M3 root and the IAC was assessed as follows: the M3 root was either apart from, tangential to, superimposed with, or inferior to the IAC. Differences between frequencies were tested using the chi-squared test. In the combined samples, only 16% of the M3s located apart from the IAC, 15% located tangential to, 61% superimposed with, and 8% inferior to the IAC. The proportion of the intimate locations had increased during the 20-year time interval from 79 to 88% (P <0.01) and especially in females (P <0.05). The vast majority of the mandibular M3s situated very close to the mandibular canal. Our results suggest that in the cohort of 20-year-old non-extraction subjects, most of the M3s are possibly at risk for inferior alveolar nerve injury at removal, as judged from the panoramic radiograph, and also the number of such teeth has increased over the 20-year period.
  • Björkman, P.; Weselius, E. -M.; Kokkonen, T.; Rauta, V.; Alback, A.; Venermo, M. (2019)
    Background and Aims: Stenosis due to intimal hyperplasia and restenosis after initially successful percutaneous angioplasty are common reasons for failing arteriovenous fistulas. The aim of this study was to evaluate the effect of drug-coated balloons in the treatment of arteriovenous fistula stenosis. Design: Single-center, parallel group, randomized controlled trial. Block randomized by sealed envelope 1:1. Materials and Methods: A total of 39 patients with primary or recurrent stenosis in a failing native arteriovenous fistulas were randomized to drug-coated balloon (n=19) or standard balloon angioplasty (n=20). Follow-up was 1year. Primary outcome measure was target lesion revascularization. Results: In all, 36 stenoses were analyzed; three patients were excluded due to technical failure after randomization. A total of 88.9% (16/18) in the drug-coated balloon group was revascularized or occluded within 1year, compared to 22.2% (4/18) of the stenoses in the balloon angioplasty group (relative risk for drug-coated balloon 7.09). Mean time-to- target lesion revascularization was 110 and 193days after the drug-coated balloon and balloon angioplasty, respectively (p=0.06). Conclusions: With 1-year follow-up, the target lesion revascularization-free survival after drug-coated balloon-treatment was clearly worse. The reason for this remains unknown, but it may be due to differences in the biological response to paclitaxel in the venous arteriovenous fistula-wall compared to its antiproliferative effect in the arterial wall after drug-coated balloon treatment of atherosclerotic occlusive lesions. Trial registration: NCT03036241
  • Björkman, Johannes; Setälä, Piritta; Pulkkinen, Ilkka; Raatiniemi, Lasse; Nurmi, Jouni (2022)
    Background: Trauma is the leading cause of death especially in children and young adults. Prehospital care following trauma emphasizes swift transport to a hospital following initial care. Previous studies have shown conflicting results regarding the effect of time on the survival following major trauma. In our study we investigated the effect of prehospital time-intervals on 30-day mortality on trauma patients that received prehospital critical care. Methods: We performed a retrospective study on all trauma patients encountered by helicopter emergency medical services in Finland from 2012 to 2018. Patients discharge diagnoses were classed into (1) trauma without traumatic brain injury, (2) isolated traumatic brain injury and (3) trauma with traumatic brain injury. Emergency medical services response time, helicopter emergency medical services response time, on-scene time and transport time were used as time-intervals and age, Glasgow coma scale, hypotension, need for prehospital airway intervention and ICD-10 based Injury Severity Score were used as variables in logistic regression analysis. Results: Mortality data was available for 4,803 trauma cases. The combined 30-day mortality was 12.1% (582/4,803). Patients with trauma without a traumatic brain injury had the lowest mortality, at 4.3% (111/2,605), whereas isolated traumatic brain injury had the highest, at 22.9% (435/1,903). Patients with both trauma and a traumatic brain injury had a mortality of 12.2% (36/295). Following adjustments, no association was observed between time intervals and 30-day mortality. Discussion: Our study revealed no significant association between different timespans and mortality following severe trauma in general. Trends in odds ratios can be interpreted to favor more expedited care, however, no statistical significance was observed. As trauma forms a heterogenous patient group, specific subgroups might require different approaches regarding the prehospital timeframes. Study type: prognostic/therapeutic/diagnostic test. (C) 2022 The Authors. Published by Elsevier Ltd.
  • Azbel, Michael; Heinänen, Mikko; Lääperi, Mitja; Kuisma, Markku (2021)
    Background The COVID-19 pandemic has had profound effects on the utilization of health care services, including Emergency Medical Services (EMS). Social distancing measures taken to prevent the spread of the disease have greatly affected the functioning of societies and reduced or halted many activities with a risk of injury. The aim of this study was to report the effects of lockdown measures on trauma-related EMS calls in the Finnish capital area. Methods We conducted a retrospective cohort study of all EMS calls in the Helsinki University Hospital (HUH) catchment area between 1 January and 31 July 2020. Calls were identified from the HUH EMS database. Calls were grouped into pre-lockdown, lockdown, and post-lockdown periods according to the restrictions set by the Finnish government and compared to the mean number of calls for the corresponding periods in 2018 and 2019. Statistical comparisons were performed using Mann-Whitney U-test for weekly numbers and percentages. Results During the study period there was a total of 70,705 EMS calls, of which 14,998 (21.2%) were related to trauma; 67,973 patients (median age 61.6 years; IQR 35.3-78.6) were met by EMS. There was no significant change in the weekly number of total or trauma-related EMS calls during the pre-lockdown period. During the lockdown period, the number of weekly total EMS calls was reduced by 12.2% (p = 0.001) and the number of trauma-related calls was reduced by 23.3% (p = 0.004). The weekly number of injured patients met by EMS while intoxicated with alcohol was reduced by 41.8% (p = 0.002). During the post-lockdown period, the number of total and trauma-related calls and the number of injured patients intoxicated by alcohol returned to previous years' levels. Conclusions The COVID-19 pandemic and social distancing measures reduced the number of trauma-related EMS calls. Lockdown measures had an especially significant effect on the number of injured patients intoxicated by alcohol met by the EMS.
  • Rentola, Raisa; Hästbacka, Johanna; Heinonen, Erkki; Rosenberg, Per H.; Häggblom, Tom; Skrifvars, Markus B. (2018)
    Arterial blood gas (ABG) analysis is the traditional method for measuring the partial pressure of carbon dioxide. In mechanically ventilated patients a continuous noninvasive monitoring of carbon dioxide would obviously be attractive. In the current study, we present a novel formula for noninvasive estimation of arterial carbon dioxide. Eighty-one datasets were collected from 19 anesthetized and mechanically ventilated pigs. Eleven animals were mechanically ventilated without interventions. In the remaining eight pigs the partial pressure of carbon dioxide was manipulated. The new formula (Formula 1) is PaCO2 = PETCO2 + k(PETO2 - PaO2) where PaO2 was calculated from the oxygen saturation. We tested the agreements of this novel formula and compared it to a traditional method using the baseline PaCO2 - ETCO2 gap added to subsequently measured, end-tidal carbon dioxide levels (Formula 2). The mean difference between PaCO2 and calculated carbon dioxide (Formula 1) was 0.16 kPa (+/- SE 1.17). The mean difference between PaCO2 and carbon dioxide with Formula 2 was 0.66 kPa (+/- SE 0.18). With a mixed linear model excluding cases with cardiorespiratory collapse, there was a significant difference between formulae (p <0.001), as well as significant interaction between formulae and time (p <0.001). In this preliminary animal study, this novel formula appears to have a reasonable agreement with PaCO2 values measured with ABG analysis, but needs further validation in human patients.
  • Kurvinen, Annika; Lohi, Jouko; Sorsa, Timo; Jalanko, Hannu; Pakarinen, Mikko P. (2016)
    Background. Intestinal failure is associated frequently with liver injury, which persists after weaning off parenteral nutrition. We compared features of liver remodeling in intestinal failure during and after weaning off parenteral nutrition. Methods. Liver biopsies and serum samples were obtained from 25 intestinal failure patients at a median age of 9.7 years (interquartile range: 4.6-18) and from age-matched control patients. Seven patients had been receiving parenteral nutrition for 53 months (22-160), and 18 patients had been weaned off parenteral nutrition 6.3 years (2.4-17) earlier, after having received parenteral nutrition for 10 months (3.3-34). Expression of alpha smooth muscle actin, collagen 1, proinflammatory cytokines, growth factors, and matrix metalloproteinases (MMPs) was measured. Results. Significant increases in immunohistochemical expression of alpha-smooth muscle actin and collagen 1 were observed predominantly in portal areas and were similar to increases seen in patients currently receiving parenteral nutrition and in patients weaned off parenteral nutrition. Gene and protein expressions of alpha-smooth muscle actin and collagen were interrelated. Gene expression of ACTA2, encoding alpha-smooth muscle actin, was increased only in patients who were receiving parenteral nutrition currently. Comparable upregulation of interleukin-1 (alpha and beta), epidermal growth factor, integrin-beta 6, and MMP9 gene expression was observed in both patient groups, irrespective of whether they were receiving parenteral nutrition currently. Liver expression and serum levels of TIMP1 and MMP7 were increased only in the patients on parenteral nutrition currently but were not increased after weaning off parenteral nutrition. Conclusion. Intestinal failure is characterized by abnormal activation of hepatic myofibroblast and accumulation of collagen both during and after weaning off parenteral nutrition. Persistent transcriptional upregulation of proinflammatory and fibrogenic cytokines after weaning off parenteral nutrition suggests that factors other than parenteral nutrition may contribute to intestinal failure associated liver disease.
  • Ajoolabady, Amir; Aslkhodapasandhokmabad, Hami; Libby, Peter; Tuomilehto, Jaakko; Lip, Gregory Y. H.; Penninger, Josef M.; Richarrdson, Des. R.; Tang, Daoli; Zhou, Hao; Wang, Shuyi; Kionsky, Daniel . J.; Kroemer, Guido; Ren, Jun (2021)
    Ferroptosis is a form of regulated cell death modality associated with disturbed iron-homeostasis and unrestricted lipid peroxidation. Ample evidence has depicted an essential role for ferroptosis as either the cause or consequence for human diseases, denoting the likely therapeutic promises for targeting ferroptosis in the preservation of human health. Ferritinophagy, a selective form of autophagy, contributes to the initiation of ferroptosis through degradation of ferritin, which triggers labile iron overload (IO), lipid peroxidation, membrane damage, and cell death. In this review, we will delineate the role of ferritinophagy in ferroptosis, and its underlying regulatory mechanisms, to unveil the therapeutic value of ferritinophagy as a target in the combat of ferroptosis to manage metabolic diseases.