Mikkeli Osteoporosis Index Identifies Fracture Risk Factors and Osteoporosis and Intervention Thresholds Parallel with FRAX

Osteoporosis Index (MOI) was developed from Fracture Index (FI), a validated fracture risk score, to identify also osteoporosis. MOI risk factors are age, weight, previous fracture, family history of hip fracture or spinal osteoporosis, smoking, shortening of the stature, and use of arms to rise from a chair. The association of these risk factors with BMD was examined in development cohorts of 300 Finnish postmenopausal women with a fracture and in a population control of 434 women aged 65–72. Validation cohorts included 200 fracture patients and a population control of 943 women aged 58–69. MOI identified femoral neck osteoporosis in these cohorts as well as the Osteoporosis Self-Assessment Tool (OST). In the pooled fracture cohort, the association of BMI-based FRAX fracture risk with MOI was good. After BMD measurement, MOI identified well FRAX hip fracture risk-based Intervention Thresholds (ITs) (AUC 0.74–0.90)

Smoking in pregnancy, adolescent mental health and cognitive performance in young adult offspring: results from a matched sample within a Finnish cohort

$\textbf{Background:}$ The association between prenatal exposure to maternal cigarette smoking (PEMCS) and adult cognition is debated, including if there are differences according to sex. We aimed to determine if there are associations between PEMCS and cognition in early adulthood in men and women and examine if observed associations were mediated by adolescent mental health factors that are associated with cognition, namely psychotic-like experiences (PLEs), inattention and hyperactivity, and other externalizing behaviors. $\textbf{Methods:}$ Participants were 471 individuals drawn from the general population-based Northern Finland 1986 Birth Cohort (NFBC 1986) followed up from pregnancy and birth to early adulthood; individuals with PEMCS were matched with those without PEMCS by socioeconomic and demographic factors. Cognitive performance in adulthood was assessed with a range of tests and their association with PEMCS was measured by sex using hierarchical linear regression, unadjusted and then controlling for potential confounders, mediators and moderators, including adolescent mental health factors. $\textbf{Results:}$ There were no associations between PEMCS and cognitive scores in females. In males, there were associations with vocabulary (beta = -0.444, 95% CI: -0.783, -0.104) and matrix reasoning (beta = -0.379, 95% CI: -0.711, -0.047). $\textbf{Conclusions:}$ While associations between PEMCS and cognition were limited, observed findings with measures of general intelligence in males contribute to suggestions of differences in response to PEMCS by sex. Furthermore, observed associations may be partly mediated by earlier inattention and hyperactivity. Findings add support to efforts aimed to eliminate smoking in pregnancy.The Northern Finland Birth Cohort 1986 is funded by the University of Oulu, University Hospital of Oulu, Academy of Finland, Sigrid Juselius Foundation, European Commission (EURO-BLCS, Framework 5 award QLG1-CT-2000- 01643), and NIH/NIMH (5R01MH63706:02). Cambridge Cognition Ltd. provided support in the form of salaries for author Jennifer H. Barnett

Predicting the outcome of hip fracture patients by using N-terminal fragment of pro-B-type natriuretic peptide

Objective: To examine the prognostic value of perioperative N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) in hip fracture patients.Design: Blinded prospective cohort study.Setting: Single centre trial at Turku University Hospital in Finland.Participants: Inclusion criterion was admittance to the study hospital due to hip fracture during the trial period of October 2009-May 2010. Exclusion criteria were the patient's refusal and inadequate laboratory tests. The final study population consisted of 182 patients.Primary and secondary outcome measures: NT-proBNP was assessed once during the perioperative period and later if clinically indicated, and troponin T (TnT) and ECG recordings were evaluated repeatedly. The short-term (30-day) and long-term (1000 days) mortalities were studied.Results: Median (IQR) follow-up time was 3.1 (0.3) years. The median (IQR) NT-proBNP level was 1260 (2298) ng/L in preoperative and 1600 (3971) ng/L in postoperative samples (p=0.001). TnT was elevated in 66 (36%) patients, and was significantly more common in patients with higher NT-proBNP. Patients with high (>2370 ng/L) and intermediate (806-2370 ng/L) NT-proBNP level had significantly higher short-term mortality compared with patients having a low (<806 ng/L) NT-proBNP level (15 vs 11 vs 2%, p=0.04), and the long-term mortality remained higher in these patients (69% vs 49% vs 27%, p<0.001). Intermediate or high NT-proBNP level (HR 7.8, 95% CI 1.03 to 59.14, p<0.05) was the only independent predictor of short-term mortality, while intermediate or high NT-proBNP level (HR 2.27, 95% CI 1.30 to 3.96, p=0.004), the presence of dementia (HR 1.74, 95% CI 1.13 to 2.66, p=0.01) and higher preoperative American Society of Anesthesiologists' (ASA) classification (HR 1.59, 95% CI 1.06 to 2.38, p=0.02) were independent predictors of long-term mortality.Conclusion: An elevated perioperative NT-proBNP level is common in hip fracture patients, and it is an independent predictor of short-term and long-term mortality superior to the commonly used clinical risk scores

Effects of cognac on coronary flow reserve and plasma antioxidant status in healthy young men

<p>Abstract</p> <p>Background</p> <p>The cardioprotective effects of certain alcoholic beverages are partly related to their polyphenol content, which may improve the vasodilatory reactivity of arteries. Effect of cognac on coronary circulation, however, remains unknown. The purpose of this randomized controlled cross-over study was to determine whether moderate doses of cognac improve coronary reactivity as assessed with cold pressor testing (CPT) and coronary flow reserve (CFR) measument.</p> <p>Methods</p> <p>Study group consisted of 23 subjects. Coronary flow velocity and epicardial diameter was assessed using transthoracic echocardiography at rest, during CPT and adenosine infusion-derived CFR measurements before drinking, after a moderate (1.2 ± 0.1 dl) and an escalating high dose (total amount 2.4 ± 0.3 dl) of cognac. To explore the bioavailability of antioxidants, the antioxidant contents of cognac was measured and the absorption from the digestive tract was verified by plasma antioxidant capacity determination.</p> <p>Results</p> <p>Serum alcohol levels increased to 1.2 ± 0.2‰ and plasma antioxidant capacity from 301 ± 43.9 μmol/l to 320 ± 25.0 μmol/l by 7.6 ± 11.8%, (p = 0.01) after high doses of cognac. There was no significant change in flow velocity during CPT after cognac ingestion compared to control day. CFR was 4.4 ± 0.8, 4.1 ± 0.9 (p = NS), and 4.5 ± 1.2 (p = NS) before drinking and after moderate and high doses on cognac day, and 4.5 ± 1.4, and 4.0 ± 1.2 (p = NS) on control day.</p> <p>Conclusion</p> <p>Cognac increased plasma antioxidant capacity, but it had no effect on coronary circulation in healthy young men.</p> <p>Trial Registration</p> <p>NCT00330213</p

Multiple formin proteins participate in glioblastoma migration

BackgroundThe prognosis of glioblastoma remains poor, related to its diffuse spread within the brain. There is an ongoing search for molecular regulators of this particularly invasive behavior. One approach is to look for actin regulating proteins that might be targeted by future anti-cancer therapy. The formin family of proteins orchestrates rearrangement of the actin cytoskeleton in multiple cellular processes. Recently, the formin proteins mDia1 and mDia2 were shown to be expressed in glioblastoma in vitro, and their function could be modified by small molecule agonists. This finding implies that the formins could be future therapeutic targets in glioblastoma.MethodsIn cell studies, we investigated the changes in expression of the 15 human formins in primary glioblastoma cells and commercially available glioblastoma cell lines during differentiation from spheroids to migrating cells using transcriptomic analysis and qRT-PCR. siRNA mediated knockdown of selected formins was performed to investigate whether their expression affects glioblastoma migration.Using immunohistochemistry, we studied the expression of two formins, FHOD1 and INF2, in tissue samples from 93 IDH-wildtype glioblastomas. Associated clinicopathological parameters and follow-up data were utilized to test whether formin expression correlates with survival or has prognostic value.ResultsWe found that multiple formins were upregulated during migration. Knockdown of individual formins mDia1, mDia2, FHOD1 and INF2 significantly reduced migration in most studied cell lines. Among the studied formins, knockdown of INF2 generated the greatest reduction in motility in vitro. Using immunohistochemistry, we demonstrated expression of formin proteins FHOD1 and INF2 in glioblastoma tissues. Importantly, we found that moderate/high expression of INF2 was associated with significantly impaired prognosis.ConclusionsFormins FHOD1 and INF2 participate in glioblastoma cell migration. Moderate/high expression of INF2 in glioblastoma tissue is associated with worse outcome. Taken together, our in vitro and tissue studies suggest a pivotal role for INF2 in glioblastoma. When specific inhibiting compounds become available, INF2 could be a target in the search for novel glioblastoma therapies.Peer reviewe

Stroke as the First Manifestation of Atrial Fibrillation

Atrial fibrillation may remain undiagnosed until an ischemic stroke occurs. In this retrospective cohort study we assessed the prevalence of ischemic stroke or transient ischemic attack as the first manifestation of atrial fibrillation in 3,623 patients treated for their first ever stroke or transient ischemic attack during 2003-2012. Two groups were formed: patients with a history of atrial fibrillation and patients with new atrial fibrillation diagnosed during hospitalization for stroke or transient ischemic attack. A control group of 781 patients with intracranial hemorrhage was compiled similarly to explore causality between new atrial fibrillation and stroke. The median age of the patients was 78.3 [13.0] years and 2,009 (55.5%) were women. New atrial fibrillation was diagnosed in 753 (20.8%) patients with stroke or transient ischemic attack, compared to 15 (1.9%) with intracranial hemorrhage. Younger age and no history of coronary artery disease or other vascular diseases, heart failure, or hypertension were the independent predictors of new atrial fibrillation detected concomitantly with an ischemic event. Thus, ischemic stroke was the first clinical manifestation of atrial fibrillation in 37% of younger (<75 years) patients with no history of cardiovascular diseases. In conclusion, atrial fibrillation is too often diagnosed only after an ischemic stroke has occurred, especially in middle-aged healthy individuals. New atrial fibrillation seems to be predominantly the cause of the ischemic stroke and not triggered by the acute cerebrovascular event

Mortality after stroke in patients with paroxysmal and chronic atrial fibrillation - The FibStroke study

Background: Recent studies have reported that patientswith paroxysmal atrial fibrillation (AF) have lower risk of thromboembolism and better prognosis than patients with chronic AF. We sought to address the differences in ischaemic events in patients with paroxysmal AF and chronic AF.Methods: The FibStroke study is a cross-sectional observational multicenter registry that included AF patients with an ischaemic stroke, TIA (transient ischaemic attack) or intracranial bleed during 2003-2012 identified from discharge registries of four Finnish hospitals. Altogether 1448 patients with paroxysmal and 1808 patients with chronic atrial fibrillation suffered a total of 707 TIA-episodes and 2549 ischaemic strokes.Results: Mortality within 30 days after the index event was significantly lower in patients with paroxysmal AF than with chronic AF (7.6% vs 16.9%, p < 0.01). At the onset of event, 62.8% of the patients with paroxysmal AF were in sinus rhythm, and these patients had better prognosis after the event compared to patients with other rhythmthan sinus rhythm(mortality 5.2% vs 15.7%, p < 0.01). In the propensity score matched analysismortality after stroke was significantly lower in patients with paroxysmal AF than in patients with chronic AF (11.6% vs 17.8%, p < 0.01), while mortality after TIA was also lower, but did not reach statistical significance (0.4% vs 1.7%, p = 0.31).Conclusions: Asignificant proportion of strokes in AF patients occur in patients with paroxysmal AF, but they have better prognosis than patients with chronic AF. The prognosis is also significantly better in patients who are in sinus rhythm at the onset of event.

Feasibility of MRI-guided transurethral ultrasound for lesion-targeted ablation of prostate cancer

Background: MRI-guided transurethral ultrasound ablation (TULSA) has been evaluated for organ-confined prostate cancer (PCa). The purpose of this study was to assess the safety and toxicity, accuracy and short-term evolution of cell-death after lesion-targeted TULSA.Methods: This prospective, registered, Phase-I treat-and-3-week-resect-study enrolled six patients with MRI-visible-biopsy-concordant PCa. Lesions were targeted using TULSA with radical intent, except near neurovascular bundles (NVB). Robot-assisted-laparoscopic-prostatectomy (RALP) was performed at 3 weeks. Post-TULSA assessments included MRI (1 and 3 weeks), adverse events and quality-of-life (QoL) to 3 weeks, followed by RALP and whole-mount-histology. Treatment accuracy and demarcation of thermal injury were assessed using MRI and histology.Results: Six patients (median age = 70 years, prostate volume = 60 ml, PSA = 8.9 ng/ml) with eight biopsy-confirmed MRI-lesions (PIRADS ≥3) were TULSA-treated without complications (median sonication and MRI-times of 17 and 117 min). Foley-catheter removal was uneventful at 2–3 days. Compared to baseline, no differences in QoL were noted at 3 weeks. During follow-up, MRI-derived non-perfused-volume covered ablated targets and increased 36% by 3 weeks, correlating with necrosis-area on histology. Mean histological demarcation between complete necrosis and outer-limit-of-thermal-injury was 1.7 ± 0.4 mm. Coagulation necrosis extended to capsule except near NVB, where 3 mm safety-margins were applied. RALPs were uncomplicated and histopathology showed no viable cancer within the ablated tumor-containing target.Conclusions: Lesion-targeted TULSA demonstrates accurate and safe ablation of PCa. A significant increase of post-TULSA non-perfused-volume was observed during 3 weeks follow-up concordant with necrosis on histology. TULSA achieved coagulation necrosis of all targeted tissues. A limitation of this treat-and-resect-study-design was conservative treatment near NVB in patients scheduled for RALP.</p