Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon

Somatostatin Receptor Expression Is Associated With Metastasis and Patient Outcome in Pulmonary Carcinoid Tumors

Context: Pulmonary carcinoids (PCs) belong to neuroendocrine tumors that often overexpress somatostatin receptors (SSTRs). This overexpression provides a molecular basis for tumor imaging and treatment with somatostatin analogs. Objective: To evaluate SSTR1 to SSTR5 distribution in a large set of PC tumors and to investigate whether the expression is associated with clinicopathological and outcome data. Design, Setting, and Patients: This retrospective study was conducted at Helsinki University Hospital and University of Helsinki. It included 178 PC tumors coupled with patients' clinical data retrieved through Finnish biobanks. After histological reclassification, tissue specimens were processed into next-generation tissue microarray format and stained immunohistochemically with monoclonal SSTR1 to SSTR5 antibodies. Main Outcome Measure: SSTR1 to SSTR5 expression in PC tumors. Results: Expression of SSTR1 to SSTR5 was detected in 52%, 75%, 56%, 16%, and 32% of the tumors, respectively. Membrane-bound staining was observed for all receptors. SSTR2 negativity and SSTR4 positivity was associated with lymph node involvement at the time of surgery (P = 0.014 and P = 0.017, respectively) and with distant metastasis (P = 0.027 and P = 0.015, respectively). SSTR3 and SSTR4 expression was associated with increased risk of shorter survival [P = 0.046, hazard ratio (HR) 4.703, 95% CI 1.027 to 21.533; and P = 0.013, HR 6.64, 95% CI 1.48 to 29.64, respectively], whereas expression of SSTR1 and SSTR2 was associated with improved outcome (P = 0.021, HR 0.167, 95% CI 0.037 to 0.765; and P = 0.022, HR 0.08, 95% CI 0.01 to 0.70, respectively). Conclusion: SSTR1 to SSTR5 expression is observed in PCs. As SSTR expression is associated with the tumor's metastatic potential and patient outcome, these receptors may offer the possibility for individualized prognosis estimation.Peer reviewe

Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

Performance of Finnish biobanks in nationwide pulmonary carcinoid tumour research

Finnish hospital-integrated biobanks administer millions of formalin-fixed paraffin-embedded tissue samples collected within the clinical diagnostics. According to the Finnish Biobank Act, these samples can be coupled with patients’ clinical follow-up data and the data retrieved from national health registries. We collected a nationwide pulmonary carcinoid tumour series from Finnish biobanks to study prognostic factors as well as to explore how the number of tumours found in the Finnish biobanks corresponds to the number of tumours registered by the Finnish Cancer Registry (FCR). Finnish biobanks identified 88% of the tumours registered by the FCR and were able to deliver 63%. The main reasons for lacking samples were paucity of resected primary tumour tissue, incompatible primary diagnosis, and the absence of tissue blocks in the archives. The main bottleneck in the sample application process was retrieving patient data. Altogether, we received 224 tumour samples with appropriate patient data and identified six prognostic factors for shorter disease-specific survival: age over 56 years at the time of diagnosis, tumour size over 2.5 cm, atypical histology, Ki-67 proliferation index higher than 2.5%, hilar/mediastinal lymph node involvement at the time of diagnosis, and the presence of metastatic disease. In conclusion, the Finnish biobank infrastructure offers excellent opportunities for tissue-based research. However, to be able to develop the biobank operations further, involving more medical knowledge in the sample and data acquisition process is a necessity. Also, when working with tissue samples collected over decades, histological expertise is essential for re-evaluation and re-classification of the samples.Peer reviewe

Hair cortisol concentrations are associated with dental anxiety during pregnancy

Dental anxiety (DA) and hair cortisol concentrations (HCC) are associated with psychological symptoms and vary during pregnancy. We aimed to examine the association between HCC and DA at two points of pregnancy. Participants were pregnant mothers (n = 533) drawn from the FinnBrain Birth Cohort Study donating a hair sample at gestational week (gwk) 24 (n = 442) and/or at delivery (n = 176) and completed questionnaires on DA. Two groups, HCC1 and HCC2, treated as separate in the analyses, were formed according to the hair sample donation time i.e., gwk24 and delivery. 85 subjects were included in both groups. MDAS, EPDS, and SCL-90 were used to measure DA, depressive and anxiety symptoms, respectively, at gwk14 for the HCC1 group and gwk34 for the HCC2 group. The association between DA and HCC was studied with a binary logistic regression model, adjusted for anxiety and depressive symptoms, age, BMI, and smoking status. Individuals with high DA had lower HCC levels at gwk24 (OR = 0.548; 95% CI = 0.35–0.86; p = 0.009), but the association was not statistically significant at the delivery (OR = 0.611; 95% CI = 0.28–1.33; p = 0.216). The independent association between HCC and DA in pregnant women suggests that long-term cortisol levels could play a role in the endogenous etiology of DA. Further studies are however, needed.This research was funded by the Academy of Finland (grant #134950 to HK and grant #308176 to LK), Jane and Aatos Erkko Foundation, Signe and Ane Gyllenberg Foundation, and State Research Grants. AJR is funded by FCT under the project PTDC/MED-NEU/29071/2017

Maternal prenatal hair cortisol is associated with prenatal depressive symptom trajectories

Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. Methods Subjects (N = 595) were drawn from the FinnBrain Birth Cohort Study. Maternal HCC was measured from hair samples collected at gestational week (gwk) 24 (HCC1, n = 467) and at delivery (HCC2, n = 222). As HCC1 and HCC2 comprised mostly of different subjects, they were considered as independent populations. Maternal PD assessments at gwks 14, 24, and 34 were the Edinburgh Postnatal Depression Scale (EPDS), the anxiety subscale of the Symptom Checklist (SCL-90), the Pregnancy-Related Anxiety Questionnaire -Revised2 (PRAQ-R2), and a daily hassles scale. Cumulative PD comprised of the mean scores of two consecutive assessments (mean1 = gwks 14 and 24; mean2 = gwks 24 and 34). In addition, EPDS and SCL scores were modelled by using growth mixture modelling to identify symptom trajectory categories. Regression models were adjusted for age, body mass index, education and use of selective serotonin/serotonin-norepinephrine reuptake inhibitor medication. Results In the adjusted regression model, higher HCC2 was related to the “consistently elevated” prenatal depressive symptoms trajectory in comparison to “consistently low” (β =.71, p =.021) and “low and increasing” (β =.82, p = .011) symptom trajectories. Additionally, the cumulative mean (mean 1) of daily hassles in relationships was associated with HCC1 (β = 0.25, p = .004). General or pregnancy-related anxiety symptoms were unrelated to HCC after adjustment for the covariates. Conclusions The assessment of cumulative or trajectory measures of PD can reveal important associations with maternal prenatal HCC, even though the associations are generally weak. Of the different dimensions of PD, prenatal trajectories of depressive symptoms were most consistently linked with end-pregnancy HCC levels.Academy of Finland (grant #134950 to HK and grant #308176 to LK), Jane and Aatos Erkko Foundation, Signe and Ane Gyllenberg Foundation, and State Research Grants. Preparation of the manuscript has been funded by Juho Vainio Foundation (PM), Finnish Brain Foundation (PM), and Yrjö Jahnsson Foundation (LK, grants #6976 and #6847). AJR is an FCT Investigator Fellow (IF/00883/2013) and is funded by projects POCI-01-0145-FEDER-016428; POCI-01-0145-FEDER-029071 and POCI-01-0145-FEDER-00703

The effect of mental health conditions on the use of oral anticoagulation therapy in patients with atrial fibrillation : the FinACAF study

Aims Little is known about the effects of mental health conditions (MHCs) on the utilization of oral anticoagulation (OAC) therapy in atrial fibrillation (AF) patients. We aimed to assess whether MHCs affect initiation of OAC therapy among AF patients with special focus on non-vitamin K antagonist oral anticoagulants (NOACs). Methods and results The Finnish AntiCoagulation in Atrial Fibrillation (FinACAF) registry included all 239 222 patients diagnosed with incident AF during 2007-18 in Finland identified from national registries covering primary to tertiary care and drug purchases. Patients with previous depression, bipolar disorder, anxiety disorder, or schizophrenia diagnosis or a fulfilled psychiatric medication prescription within the year preceding the AF diagnosis were classified to have any MHC. The main outcome was OAC initiation, defined as first fulfilled OAC prescription after AF diagnosis. The patients' mean age was 72.7 years and 49.8% were female. The prevalence of any MHC was 19.9%. A lower proportion of patients with any MHC compared with those without MHCs were initiated on OAC therapy (64.9% vs. 73.3%, P < 0.001). Any MHC was associated with lower incidence of OAC initiation [adjusted subdistribution hazard ratio (aSHR) 0.867; 95% confidence interval (CI) 0.856-0.880], as were depression (aSHR 0.868; 95% CI 0.856-0.880), bipolar disorder (aSHR 0.838; 95% CI 0.824-0.852), anxiety disorder (aSHR 0.840; 95% CI 0.827-0.854), and schizophrenia (aSHR 0.838; 95% CI 0.824-0.851), during the entire follow-up. Any MHC remained associated with impaired incidence of OAC initiation also in the NOAC era during 2015-18 (aSHR 0.821; 95% CI 0.805-0.837). Conclusion MHCs are common among AF patients, and they are associated with a lower rate of OAC initiation even during the NOAC era.Peer reviewe