IV Thrombolysis-Bridging and Endovascular Treatment for Occlusive Internal Carotid Artery Dissection with Tandem Occlusion

Compared to other etiologies of ischemic stroke, occlusive internal carotid artery dissection responds worse to intravenous (IV) thrombolysis. Intracranial tandem occlusion is a predictor of poor outcome. A direct endovascular approach has been proposed as a safe and probably superior alternative to IV thrombolysis. However, it may lead to considerable treatment delays. We used rapidly initiated IV thrombolysis-bridging and subsequent endovascular treatment in two patients with severe hemispheric ischemia due to occlusive internal carotid artery dissection with tandem occlusion and achieved good outcomes. Minimizing recanalization times likely improves patient outcome and IV thrombolysis-bridging may be a reasonable strategy to achieve this. The positive initial results obtained with endovascular approaches and IV thrombolysis-bridging in this patient group deserve further scientific exploration

Elevated CRP levels indicate poor progression-free and overall survival on cancer patients treated with PD-1 inhibitors

Background Anti-PD-(L)1 agents are standard of care treatments in various cancers but predictive factors for therapy selection are limited. We hypothesised that markers of systemic inflammation would predict adverse outcomes in multiple cancers treated with anti-PD-(L)1 agents. Material and methods Discovery cohort consisted of patients who were treated with anti-programmed cell death protein-1 (PD-1) agents for advanced melanoma (MEL), non-small cell lung cancer (NSCLC) or renal and bladder cancers (GU) at Oulu University Hospital and had pretreatment C reactive protein (CRP), or neutrophil/lymphocyte values available. As a validation cohort, we collected patients treated with anti-PD-1 agents from three other hospitals in Finland. Results In the discovery cohort (n=56, MEL n=23, GU n=17, NSCLC n=16), elevated CRP over the upper limit of normal (ULN) (>10mg/mL) indicated poor progression-free (PFS; p=0.005) and overall survival (OS; p=0.000004) in the whole population and in MEL subgroup. Elevated neutrophil-to-lymphocyte ratio (>2.65) also indicated inferior PFS (p=0.02) and OS (p=0.009). In the validation cohort (n=107,MEL n=44, NSCLC n=42, GU n=17, other n=4), CRP over ULN also was a strong indicator for poor PFS (p=0.0000008), and OS (p=0.000006) in the whole population, and in MEL and NSCLC also. Conclusions Systemic inflammation suggested by elevated CRP is a very strong indicator for adverse prognosis on patients treated with anti-PD-(L)1 agents and has a potential negative predictive value for treatment with anti-PD-(L)1 agents. Prospective trials should investigate whether patients with elevated CRP gain any significant benefit from anti-PD-1 therapy.Peer reviewe

The prognostic and predictive roles of plasma C-reactive protein and PD-L1 in non-small cell lung cancer

Background: Anti-PD-(L)1 agents have revolutionized the treatment paradigms of non-small cell lung cancer (NSCLC), while predictive biomarkers are limited. It has been previously shown that systemic inflammation, indicated by elevated C-reactive protein (CRP) level, is associated with a poor prognosis in anti-PD-(L)1 treated. The aim of the study was to analyze the prognostic and predictive value of CRP in addition to traditional prognostic and predictive markers and tumor PD-L1 score. Methods: We identified all NSCLC patients (n = 329) who had undergone PD-L1 tumor proportion score (TPS) analysis at Oulu University Hospital 2015–22. CRP levels, treatment history, immune checkpoint inhibitor (ICI) therapy details, and survival were collected. The patients were categorized based on CRP levels (≤10 vs. >10) and PD-L1 TPS scores (10) carried a high negative predictive value with a median PFS of 4.11 months (CI 95% 0.00–9.63), which was similar to patients with low PD-L1 (4.11 months, CI 95% 2.61–5.60). Conclusions: Adding plasma CRP levels to PD-L1 TPS significantly increased the predictive value of sole PD-L1. Furthermore, patients with high CRP beard little benefit from anti-PD-(L)1 therapies independent of PD-L1 score. The study highlights the combined evaluation of plasma CRP and PD-L1 TPS as a negative predictive marker for ICI therapies.Peer reviewe

Personality and Dietary Intake - Findings in the Helsinki Birth Cohort Study

Peer reviewe

Metabolic profiling of alcohol consumption in 9778 young adults

Background: High alcohol consumption is a major cause of morbidity, yet alcohol is associated with both favourable and adverse effects on cardiometabolic risk markers. We aimed to characterize the associations of usual alcohol consumption with a comprehensive systemic metabolite profile in young adults. Methods: Cross-sectional associations of alcohol intake with 86 metabolic measures were assessed for 9778 individuals from three population-based cohorts from Finland (age 24-45 years, 52% women). Metabolic changes associated with change in alcohol intake during 6-year follow-up were further examined for 1466 individuals. Alcohol intake was assessed by questionnaires. Circulating lipids, fatty acids and metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. Results: Increased alcohol intake was associated with cardiometabolic risk markers across multiple metabolic pathways, including higher lipid concentrations in HDL subclasses and smaller LDL particle size, increased proportions of monounsaturated fatty acids and decreased proportion of omega-6 fatty acids, lower concentrations of glutamine and citrate (P<0.001 for 56 metabolic measures). Many metabolic biomarkers displayed U-shaped associations with alcohol consumption. Results were coherent for men and women, consistent across the three cohorts and similar if adjusting for body mass index, smoking and physical activity. The metabolic changes accompanying change in alcohol intake during follow-up resembled the cross-sectional association pattern (R-2 = 0.83, slope = 0.7260.04). Conclusions: Alcohol consumption is associated with a complex metabolic signature, including aberrations in multiple biomarkers for elevated cardiometabolic risk. The metabolic signature tracks with long-term changes in alcohol consumption. These results elucidate the double-edged effects of alcohol on cardiovascular risk.Peer reviewe

Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events

Background: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. Methods: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. Results: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT −/AE + group, 26.7% in the RT −/AE − group and 18.3% in the RT + /AE − group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT −/AE − and RT + /AE − groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT −/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582–0.935; p = 0.012, and HR 0.620; 95% CI 0.499–0.769; p < 0.001, respectively). Conclusions: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.Peer reviewe

Metabolic Signatures of Adiposity in Young Adults : Mendelian Randomization Analysis and Effects of Weight Change

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Common Inflammation-Related Candidate Gene Variants and Acute Kidney Injury in 2647 Critically Ill Finnish Patients

Acute kidney injury (AKI) is a syndrome with high incidence among the critically ill. Because the clinical variables and currently used biomarkers have failed to predict the individual susceptibility to AKI, candidate gene variants for the trait have been studied. Studies about genetic predisposition to AKI have been mainly underpowered and of moderate quality. We report the association study of 27 genetic variants in a cohort of Finnish critically ill patients, focusing on the replication of associations detected with variants in genes related to inflammation, cell survival, or circulation. In this prospective, observational Finnish Acute Kidney Injury (FINNAKI) study, 2647 patients without chronic kidney disease were genotyped. We defined AKI according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We compared severe AKI (Stages 2 and 3, n = 625) to controls (Stage 0, n = 1582). For genotyping we used iPLEX(TM) Assay (Agena Bioscience). We performed the association analyses with PLINK software, using an additive genetic model in logistic regression. Despite the numerous, although contradictory, studies about association between polymorphisms rs1800629 in TNFA and rs1800896 in IL10 and AKI, we found no association (odds ratios 1.06 (95% CI 0.89-1.28, p = 0.51) and 0.92 (95% CI 0.80-1.05, p = 0.20), respectively). Adjusting for confounders did not change the results. To conclude, we could not confirm the associations reported in previous studies in a cohort of critically ill patients.Peer reviewe

Heme oxygenase-1 repeat polymorphism in septic acute kidney injury

Acute kidney injury (AKI) is a syndrome that frequently affects the critically ill. Recently, an increased number of dinucleotide repeats in the HMOX1 gene were reported to associate with development of AKI in cardiac surgery. We aimed to test the replicability of this finding in a Finnish cohort of critically ill septic patients. This multicenter study was part of the national FINNAKI study. We genotyped 300 patients with severe AKI (KDIGO 2 or 3) and 353 controls without AKI (KDIGO 0) for the guanine-thymine (GTn) repeat in the promoter region of the HMOX1 gene. The allele calling was based on the number of repeats, the cut off being 27 repeats in the S-L (short to long) classification, and 27 and 34 repeats for the S-M-L2 (short to medium to very long) classification. The plasma concentrations of heme oxygenase-1 (HO-1) enzyme were measured on admission. The allele distribution in our patients was similar to that published previously, with peaks at 23 and 30 repeats. The S-allele increases AKI risk. An adjusted OR was 1.30 for each S-allele in an additive genetic model (95% CI 1.01-1.66; p = 0.041). Alleles with a repeat number greater than 34 were significantly associated with lower HO-1 concentration (p<0.001). In septic patients, we report an association between a short repeat in HMOX1 and AKI risk

Syitä yli 25-vuotiaiden ja synnyttäneiden lisääntyneisiin raskaudenkeskeytyksiin : Lahden kaupungin perusterveydenhuollon ammattilaisten näkökulmia

Tiainen, Satu & Tuukkala, Sanna. Syitä yli 25-vuotiaiden ja synnyttäneiden lisääntynei-siin raskaudenkeskeytyksiin – Lahden kaupungin perusterveydenhuollon ammattilaisten näkökulmia. Lahti, syksy 2009, 46 s., 3 liitettä. Diakonia-ammattikorkeakoulu/Lahden ammattikorkeakoulu, Sosiaali- ja terveysala, Hoitotyön koulutusohjelma, Terveydenhoitotyön suuntautumisvaihtoehto, terveydenhoitaja (AMK) Raskaudenkeskeytykset ovat lisääntyneet huomattavasti Lahdessa erityisesti yli 25-vuotiaiden ja synnyttäneiden naisten keskuudessa. Ehkäisyneuvonnan resursseja on lisätty ja ehkäisyvalmisteiden saanti on helpottunut, mutta raskaudenkeskeytysten määrä ei ole vähentynyt. Suomessa suurin osa raskaudenkeskeytyksistä tehdään sosiaalisten syiden perusteella, kuitenkin raskaudenkeskeytykseen johtavista tekijöistä on olemassa vain vähän tietoa. Tutkimus sai alkunsa työelämän tarpeesta, Lahden kaupungin Sosiaali- ja terveystoimesta. Tutkimuksen tarkoituksena oli tuottaa tietoa siitä miksi raskaudenkeskeytykset ovat yleistyneet yli 25-vuotiaiden ja synnyttäneiden naisten keskuudessa perusterveydenhuollon ammattilaisten näkökulmasta. Tarkoituksena oli myös selvittää, miten terveydenhuollon ammattilaiset kehittäisivät ehkäisyneuvontaa, jotta kyseisten naisten raskaudenkeskeytykset vähenisivät. Tutkimuksesta saadun tiedon tavoitteena on kehittää Lahden perusterveydenhuollon ehkäisyneuvontaa ja vähentää yli 25-vuotiaiden ja synnyttäneiden raskaudenkeskeytysten määrää. Tutkimusmenetelmänä käytettiin kvalitatiivista eli laadullista tutkimusta. Aineisto kerättiin teemahaastattelujen avulla. Haastatteluun osallistui viisi terveydenhoitajaa ja kaksi lääkäriä, jotka työskentelevät Lahden kaupungin perusterveydenhuollossa. Aineiston analyysissä käytettiin sisällönanalyysia. Yleisin esille tullut syy yli 25-vuotiaiden ja synnyttäneiden naisten raskaudenkeskeytyksiin oli välinpitämättömyys. Ihmisillä on nykyään paljon tietoa ja ehkäisyvalmisteita saatavilla, mutta silti usein raskaudenkeskeytyksien syynä on hoitamaton ehkäisy. Sosiaaliset perusteet olivat yleisimpiä syitä raskaudenkeskeytyksiin. Niistä merkittävimpiä olivat parisuhteiden vaihtuminen, pitkät opiskeluajat, urakeskeisyys ja taloudelliset syyt. Palveluiden saannin vaikeutta pidettiin yhtenä syynä raskaudenkeskeytyksiin. Kehittä-misehdotuksena nähtiin poikien ja miesten huomioiminen ehkäisyneuvonnassa. Yhteistyön lisäämistä ehkäisyneuvolan ja äitiysneuvolan välillä sekä äitiysneuvolan terveydenhoitajien tiedon lisäämistä ehkäisyasioista pidettiin haastatteluissa yhtenä kehittämisehdotuksena. Mediassa toivottiin otettavan enemmän esille ehkäisyasioita. Ehkäisyä tulisi korostaa mediassa osana terveydestä huolehtimista eikä keskittyä ehkäisyvalmisteiden haittavaikutuksiin. Tutkimustulosten perusteella ihmisillä on tietoa ehkäisymenetelmistä, mutta välinpitämättömän suhtautumisen vuoksi raskaudenkeskeytykset lisääntyvät edelleen. Nopea palveluihin pääsy ja äitiysneuvolan työntekijöiden ehkäisyneuvontataitojen kehittäminen vähentäisivät mahdollisesti raskaudenkeskeytysten määrää. Asiasanat: abortti, ehkäisyneuvonta, kehittäminen, neuvolatTiainen, Satu & Tuukkala, Sanna. Causes of increased abortions of over 25 year old women and women who have given birth – perspectives of health care employees in Lahti municipality. Lahti autumn 2009, 46 pages, 3 appendices. Diaconia Polytechnic/Lahti University of Applied Sciences, Faculty of Social and Health Care, Degree Programme in Health Care. The number of abortions has increased significantly especially among over 25 year old women and women who have given birth despite contraceptive options and prevention counseling increase. The major part of abortions are based on social motives. Neverthe-less, there is only a little knowledge about the causes of abortions. The work was commissioned by the social and health workers of Lahti municipality. The objective of this study was to examine the causes of increased abortions of over 25 year old women and women who have given birth. The objective was also to research employees´ methods to improve prevention counseling and decrease the amount of abortions. The results of the study can be used to improve prevention counseling of health care in Lahti municipality and decrease the amount of abortions of over 25 year old women and women who have given birth. This study is qualitative. The material was collected by a theme interview. Five public health nurses and two doctors were interviewed for the study. All of them work in the health care unit of Lahti municipality. An analysis of the content was used in the analysis of the material. The disregard was the most general cause of abortions of 25 year old women and women who have given birth. Nowadays people have a lot of information and contraceptives are available. Nevertheless, the cause of abortions is commonly the lack of prevention. Social motives were the most general cause for abortions. The most notable motives were changes in relationships, importance of a career and financial motives. A difficulty to acquire health services was also a cause. Based on the study, men and boys should be noticed and motivated in prevention counseling. The employees of maternity clinics should be given more information on prevention counseling. Also in the study there was hope for more co-operation between the maternity clinics and the prevention counseling clinic. Based on the study, it is advisable to talk about prevention in media. It should be discussed as part of taking care of health instead of concentrating on disadvantages. The results of the study prove that people have information about contraceptives. Still abortions increase because of careless attitudes. Acquiring services quickly and improving prevention counseling skills of maternity clinic employees would potentially decrease the amount of abortions. Keywords: abortion, prevention counselin