Machine learning-based dynamic mortality prediction after traumatic brain injury

Our aim was to create simple and largely scalable machine learning-based algorithms that could predict mortality in a real-time fashion during intensive care after traumatic brain injury. We performed an observational multicenter study including adult TBI patients that were monitored for intracranial pressure (ICP) for at least 24 h in three ICUs. We used machine learning-based logistic regression modeling to create two algorithms (based on ICP, mean arterial pressure [MAP], cerebral perfusion pressure [CPP] and Glasgow Coma Scale [GCS]) to predict 30-day mortality. We used a stratified crossvalidation technique for internal validation. Of 472 included patients, 92 patients (19%) died within 30 days. Following cross-validation, the ICP-MAP-CPP algorithm's area under the receiver operating characteristic curve (AUC) increased from 0.67 (95% confidence interval [CI] 0.60-0.74) on day 1 to 0.81 (95% CI 0.75-0.87) on day 5. The ICP-MAP-CPP-GCS algorithm's AUC increased from 0.72 (95% CI 0.64-0.78) on day 1 to 0.84 (95% CI 0.78-0.90) on day 5. Algorithm misclassification was seen among patients undergoing decompressive craniectomy. In conclusion, we present a new concept of dynamic prognostication for patients with TBI treated in the ICU. Our simple algorithms, based on only three and four main variables, discriminated between survivors and non-survivors with accuracies up to 81% and 84%. These open-sourced simple algorithms can likely be further developed, also in low and middleincome countries.Peer reviewe

A prospective study of the relationship between prediagnostic Human Papillomavirus seropositivity and HPV DNA in subsequent cervical carcinomas

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2–8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA

Machine learning-based dynamic mortality prediction after traumatic brain injury

Our aim was to create simple and largely scalable machine learning-based algorithms that could predict mortality in a real-time fashion during intensive care after traumatic brain injury. We performed an observational multicenter study including adult TBI patients that were monitored for intracranial pressure (ICP) for at least 24 h in three ICUs. We used machine learning-based logistic regression modeling to create two algorithms (based on ICP, mean arterial pressure [MAP], cerebral perfusion pressure [CPP] and Glasgow Coma Scale [GCS]) to predict 30-day mortality. We used a stratified crossvalidation technique for internal validation. Of 472 included patients, 92 patients (19%) died within 30 days. Following cross-validation, the ICP-MAP-CPP algorithm's area under the receiver operating characteristic curve (AUC) increased from 0.67 (95% confidence interval [CI] 0.60-0.74) on day 1 to 0.81 (95% CI 0.75-0.87) on day 5. The ICP-MAP-CPP-GCS algorithm's AUC increased from 0.72 (95% CI 0.64-0.78) on day 1 to 0.84 (95% CI 0.78-0.90) on day 5. Algorithm misclassification was seen among patients undergoing decompressive craniectomy. In conclusion, we present a new concept of dynamic prognostication for patients with TBI treated in the ICU. Our simple algorithms, based on only three and four main variables, discriminated between survivors and non-survivors with accuracies up to 81% and 84%. These open-sourced simple algorithms can likely be further developed, also in low and middleincome countries

Mikrobilääkeresistenssi ja -jäämät nautatilalla - vaikutukset ympäristöön ja terveyteen (NAMI)

Tässä Ruokaviraston (ennen Elintarviketurvallisuusvirasto Evira), Luken ja SYKEn yhteisprojektissa tutkittiin mikrobilääkejäämien ja resistenttien suolistobakteerien kulkeutumista lääkityistä lypsylehmistä navettaympäristön kautta lantavarastoihin. Lisäksi arvioitiin niiden leviämistä lannan peltolevitysten välityksellä luonnon eliöihin sekä elintarviketuotantoketjussa. Projektissa tutkittiin myös anaerobisen mesofiilisen mädätyksen vaikutuksia lannassa oleviin mikrobilääkejäämiin ja resistentteihin suolistobakteereihin sekä toisaalta lannan mikrobilääkejäämien vaikutusta mädädysprosessin toimintaan. Lisäksi arvioitiin erilaisten lannan prosessointitapojen elinkaarisia ympäristövaikutuksia sekä vaikutuksia mikrobilääkejäämiin ja -resistenssiin. Resistentit ja moniresistentit suolistobakteerit kulkeutuivat lypsykarjatilalla lantavarastoihin, mutta ne eivät rikastuneet lantaketjussa. Lypsykarjan lietelannasta mitattiin hyvin pieniä pitoisuuksia mikrobilääkkeitä. Lääkittyjen eläinten sonnasta ja virtsasta taas mitattiin hoidon aikana hyvin korkeita pitoisuuksia mikrobilääkejäämiä, jolloin niistä muodostuvissa (kuivissa) lannoissa voi olla korkeita paikallisia pitoisuuksia mikrobilääkkeitä. Suomessa myös mikrobilääkkeillä lääkittyjen eläinten lannat levitetään pääosin käsittelemättöminä kasvinravinteiksi pelloille, jolloin lannan mukana voi levitä mikrobilääkejäämiä ja resistenttejä suolistobakteereita. Luonnon eliöt voivat altistua lannassa oleville mikrobilääkkeille ja resistenteille suolistobakteereille myös Suomen olosuhteissa. Lääkittyjen eläinten lantojen lannoitekäyttöä käsittelemättömänä tulisi arvioida kriittisesti. Mesofiilinen anaerobinen mädätys voi vähentää mikrobilääkejäämiä lannasta, mutta ei välttämättä hajota niitä. Se vähentää elävien suolistobakteerien määrää lannassa, mutta merkittävää vaikutusta resistenttien E. coli -bakteerien osuuteen ei havaittu. Erilaiset lannankäsittelytavat voivat kuitenkin soveltua – ravinteiden kierrätyksen ja energiantuoton lisäksi – mikrobilääkejäämien ja resistenssin torjumiseen, ja niitä tulisikin tässä tarkoituksessa tutkia tarkemmin Suomessa.I detta samprojekt mellan Livsmedelsverket (före detta Livsmedelssäkerhetsverket Evira), Luke och SYKE undersöktes spridningen av resthalter av antimikrobiella läkemedel och resistenta tarmbakterier från behandlade mjölkkor till gödsellager via ladugårdsmiljön. Därtill uppskattades spridningen till organismer i naturen via gödselspridning på åkrar samt i livsmedelskedjan. I projektet undersöktes även effekten av anaerob mesofil rötning på resthalter av antimikrobiella medel i gödsel och resistenta tarmbakterier samt även effekten av resthalter av antimikrobiella medel på rötningsprocessen. Dessutom analyserades livscykeln för miljöpåverkan av de olika gödselbearbetningsmetoderna samt effekterna på resthalter av antimikrobiella medel och resistens. Resistenta och multiresistenta tarmbakterier spreds på mjölkgården till gödsellagren, men anrikades inte i gödselkedjan. Mycket små halter av antimikrobiella medel uppmättes i mjölkkornas flytgödsel. Men mycket höga resthalter av antimikrobiella medel uppmättes i gödsel och urin medan djuren behandlades, och då kan det finnas höga lokala halter av antimikrobiella medel i deras (torr)gödsel. I Finland sprids gödsel även av antibiotikabehandlade djur till största delen obehandlad som växtnäring på åkrar, och då kan resthalter av antimikrobiella medel och resistenta tarmbakterier spridas med gödseln. Organismer i naturen kan utsättas för antimikrobiella medel i gödsel och resistenta tarmbakterier även i finländska förhållanden. Användningen av obehandlad gödsel från medicinerade djur borde utvärderas kritiskt. Mesofil anaerob rötning kan minska på mängden resthalter av antimikrobiella medel i gödseln, men bryter inte nödvändigtvis ned dem. Den minskar på mängden levande tarmbakterier i gödseln, men ingen betydande effekt på andelen resistenta E.coli-bakterier påvisades. Olika sätt att behandla gödsel kan ändå, utöver återvinning av näringsämnen och energiproduktion, lämpa sig för bekämpning av antimikrobiella resthalter och resistens, och de borde undersökas mera detaljerat i Finland i det syftet.This study was conducted by Finnish Food Authority (formerly Finnish Food Safety Authority Evira), Natural Resources Institute Finland Luke and Finnish Environment Institute SYKE in 2015–2018. The aims of the study were to examine how antimicrobial residues and antimicrobial-resistant E. coli bacteria spread via the manure chain from the dairy cows treated with antimicrobials to the farm environment and manure storages. Furthermore, the dissemination routes to the surrounding environment, ecosystems and back to the food chain in Finnish conditions were profiled. The effect of mesophilic anaerobic digestion process on the level of antimicrobial residues and antimicrobial-resistant E. coli was examined and, conversely, the effect of antimicrobial residues on the process as well. Finally, the life-cycle of different manure handling and processing methods, and their potential effects on nutrient recycling, energy production, antimicrobial residues and resistant bacteria were evaluated. Resistant and multi-resistant E. coli spread to the manure storages, although enrichment in their proportion over the manure chain was not detected. Only minor concentrations of antimicrobial residues were measured from the liquid manure. Instead, very high concentrations of antimicrobial residues were measured from the faeces, urine and milk of dairy cows medicated with antimicrobials, which may lead to high local concentrations in (dry) manures composed of them. In Finland, there is no withdrawal period for manure of medicated animals to be used as a fertilizer. Therefore, manures may contain antimicrobial residues, as well as resistant bacteria, which disseminate to the environment when applied to the fields. Animals and plants may be exposed to antimicrobial residues and resistant bacteria in agricultural and natural ecosystems in Finnish conditions as well. Therefore, fertilizer usage of faeces, urine and milk excreted by animals treated with antimicrobials should be subjected to critical assessment. Treating the manure with mesophilic anaerobic digestion may reduce the concentration of antimicrobial residues but does not necessarily destroy them. Furthermore, the process reduced the number of total E. coli bacteria, although it did not have an effect on the proportion of resistant E. coli. Along with energy production and nutrient recycling, different manure handling and processing methods may, however, be suitable for destroying and reducing antimicrobial residues and resistant bacteria from manure, and substantially reduce the emission of antimicrobial residues and resistant bacteria to the environment, as well as to the food chain. The aspect of tackling the spread of antimicrobial resistance is to be considered when manure processing methods are developed in Finland

Increasing prevalence and high incidence of celiac disease in elderly people: A population-based study

<p>Abstract</p> <p>Background</p> <p>Celiac disease may emerge at any age, but little is known of its appearance in elderly people. We evaluated the prevalence of the condition in individuals over 55 years of age, and determined the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s).</p> <p>Methods</p> <p>The study based on prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002. A second screening in the same population was carried out in 2005, comprising now 2216 individuals. Positive tissue transglutaminase antibodies were confirmed with small bowel biopsy.</p> <p>Results</p> <p>Within three years the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. Five new cases were found among patients previously seronegative; two had minor abdominal symptoms and three were asymptomatic. The incidence of celiac disease in 2002–2005 was 0.23%, giving an annual incidence of 0.08% in this population.</p> <p>Conclusion</p> <p>The prevalence of celiac disease was high in elderly people, but the symptoms were subtle. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may develop even in the elderly. Increased alertness to the disorder is therefore warranted.</p

Finnish study of intraoperative irrigation versus drain alone after evacuation of chronic subdural haematoma (FINISH): a study protocol for a multicentre randomised controlled trial

Introduction Chronic subdural haematomas (CSDHs) are one of the most common neurosurgical conditions. The goal of surgery is to alleviate symptoms and minimise the risk of symptomatic recurrences. In the past, reoperation rates as high as 20%-30% were described for CSDH recurrences. However, following the introduction of subdural drainage, reoperation rates dropped to approximately 10%. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural drainage. Yet, the role of intraoperative irrigation has not been established. If there is no difference in recurrence rates between intraoperative irrigation and no irrigation, CSDH surgery could be carried out faster and more safely by omitting the step of irrigation. The aim of this multicentre randomised controlled trial is to study whether no intraoperative irrigation and subdural drainage results in non-inferior outcome compared with intraoperative irrigation and subdural drainage following burr-hole craniostomy of CSDH.Methods and analysis This is a prospective, randomised, controlled, parallel group, non-inferiority multicentre trial comparing single burr-hole evacuation of CSDH with intraoperative irrigation and evacuation of CSDH without irrigation. In both groups, a passive subdural drain is used for 48hours as a standard of treatment. The primary outcome is symptomatic CSDH recurrence requiring reoperation within 6months. The predefined non-inferiority margin for the primary outcome is 7.5%. To achieve a 2.5% level of significance and 80% power, we will randomise 270 patients per group. Secondary outcomes include modified Rankin Scale, rate of mortality, duration of operation, length of hospital stay, adverse events and change in volume of CSDH.Ethics and dissemination The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District (HUS/3035/2019 238) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations.Trial registration number NCT04203550</div

MMP-9/RECK imbalance: a mechanism associated with high-grade cervical lesions and genital infection by Human Papillomavirus (HPV) and Chlamydia trachomatis

"Manuscript"BACKGROUND: Matrix metalloproteinases (MMP) are important enzymes in the tumor microenvironment associated with progression of cervical intraepithelial neoplasia (CIN) toward squamous cell carcinoma (SCC) of the cervix. However, the role of MMPs in the inflammatory process associated with Chlamydia trachomatis infection concomitant with the carcinogenic process driven by HPV has not yet been addressed. In the present study, we analyzed the state of the MMP-9-RECK axis in cervical carcinogenesis. METHODS: The levels of MMP-9 and RECK expression were analyzed by immunocytochemistry in liquid-based cytology samples from 136 women with high-grade cervical lesions (CIN2/CIN3) and cervical SCC diagnosed by LLETZ, and in 196 women without cervical neoplasia or CIN1. Real-time qPCR was performed to analyze expression of MMP-9 and RECK in 15 cervical samples. The presence of HPV-DNA and other genital pathogens was evaluated by PCR. RESULTS: We found a higher expression of MMP-9 [OR, 4.2; 95% confidence interval (CI), 2.2-7.8] and lower expression of RECK (OR, 0.4; 95% CI, 0.2-0.7) in women with CIN2/CIN3/SCC when compared with women from the control group (no neoplasia/CIN1). A statistically significant association was also found between MMP-9/RECK imbalance and infection by alpha-9 HPV and C. trachomatis. The prevalence of C. trachomatis infection was significantly higher in women with high-grade cervical disease (OR, 3.7; 95% CI, 1.3-11.3). CONCLUSIONS: MMP-9/RECK imbalance in cervical smears is significantly associated with high-grade cervical diseases and infection by alpha-9 HPV and C. trachomatis. IMPACT: MMP-9/RECK imbalance during cervical inflammation induced by C. trachomatis might play a role in HPV-mediated cervical carcinogenesis.This work was supported by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), numbers 2008/03232-1 (to L.L. Villa) and 2012/09746-2 (to M.G. Discacciati and S.S. Maria-Engler) and National Counsel of Technological and Scientific Development pharmaceutical innovation (CNPQ-INCT-if; to S.S. Maria-Engler)