Immunological changes and increased expression of myxovirus resistance protein a in thyroid tissue of patients with recent onset and untreated Graves' disease

Background: Few studies have systematically examined the immune cells that infiltrate thyroid tissue at the time of the onset of Graves&#39; disease (GD). The role of viruses in the pathogenesis of autoimmune thyroid diseases is controversial. The present study analyzed inflammatory responses with respect to signs of virus infection. Methods: Thyroid tissue was obtained from 22 patients with newly diagnosed and untreated GD, 24 patients with chronic GD, and 24 controls. Inflammation was assessed by immunostaining for CD4+ and CD8+ T cells, plasma cells (CD138+), and plasmacytoid dendritic cells (PDCs). The production of interferon-inducible myxovirus resistance protein A (MxA) was analyzed as a sign of virus infection. Results: The degree of thyroid inflammation and fibrosis was significantly higher in both patient groups compared with that in controls. The number of CD4+ T cells and plasma cells (activated B cells) was significantly higher in both patient groups. CD8+ cells were only present in patients with chronic disease. MxA expression and the number of PDCs increased only in patients with newly diagnosed GD. There was a strong positive correlation between the number of PDCs and the number of MxA+ leucocytes. Conclusion: The increase in CD8+ T cells during the chronic stage of GD suggests that they may play a role in progression of the autoimmune process from early to chronic thyroiditis. Upregulation of MxA expression during the early stages of the disease, and the positive correlation between the number of PDCs and the number of MxA+ leucocytes, suggests that activated PDCs secrete type I IFNs at the lesion site, possibly in response to viral infection. &nbsp;</p

Analysis of pancreas tissue in a child positive for islet cell antibodies

Conclusions/interpretation These observations suggest that positivity for ICA alone, even when lasting for more than 1 year, is not associated with inflammatory changes in the islets. However, it is most likely that the pancreatic islets were infected by an enterovirus in this child

Maternal risk factors for gastroschisis: A population‐based case–control study

BackgroundGastroschisis is an open abdominal wall defect with low mortality but significant morbidity. The prevalence has been increasing worldwide for the past decades. Several risk factors for gastroschisis have been identified, but no clear reason for increasing prevalence has been found. In our study, we aimed to assess and identify maternal risk factors for gastroschisis.MethodsIn our nationwide register‐based case–control study, we identified all gastroschisis cases in the Finnish Register of Congenital Malformations from 2004 to 2014. Information on drug prescriptions and purchases was received from Drugs and Pregnancy database. Five healthy age‐matched controls from the same geographical region were randomly selected for each case. Conditional logistic regression was used to evaluate different risk factors.ResultsOne‐hundred‐eighty‐eight cases of gastroschisis were identified and compared with 910 matched controls. Nulliparity was a significant risk factor for gastroschisis, aOR 2.00 (95% CI 1.29–3.11) whereas obesity was protective, aOR 0.35 (95% CI 0.15–0.83). Smoking appeared to increase the risk for gastroschisis, aOR 1.32 (95% CI 0.88–1.97). The mean maternal age of newborns with gastroschisis was significantly lower than average (p  ConclusionAs in previous studies, nulliparity and young maternal age were significant risk factors for gastroschisis. Maternal obesity significantly reduced the risk of gastroschisis regardless of maternal age and gestational diabetes.</p

Omphalocele in Finland from 1993 to 2014: Trends, Prevalence, Mortality, and Associated Malformations-A Population-Based Study

Introduction The aim of this study is to assess the changes in prevalence, mortality and termination pregnancy of omphalocele, and to identify associated anomalies.Materials and Methods A population-based nationwide register study. All cases with omphalocele were identified in the Finnish Register of Congenital Malformations and the Care Register for Health Care from 1993 to 2014 including live births, stillbirths, and terminations of pregnancy due to fetal anomalies. Associated anomalies were recorded and analyzed, and perinatal and infant mortality and prevalence were calculated.Results There were 600 cases with omphalocele including 229 live births, 39 stillbirths, and 332 (55%) abortions. Birth prevalence in Finland was 1.96 per 10,000 births with no consistent trend over time. However, total prevalence was much higher (4.71/10,000) because more than half of these families chose option for the termination of pregnancy. Omphalocele is often complicated with other anomalies; most commonly chromosomal abnormalities (9.3%), heart defects (6.3%), central nervous system anomalies (3.0%), gastrointestinal, and urogenital malformations (both 2.0%). Proportion of chromosomal and central nervous system abnormalities were even higher in terminated pregnancies. Overall infant mortality was 22%. Total 1-year survival rates for isolated omphalocele, cases with multiple anomalies and neonates with chromosomal defects were 80, 88, and 17%, respectively.Conclusion Omphalocele is a rare congenital anomaly, often associated with other malformations. Our data suggest that isolated cases may be more common than previously thought. In the absence of chromosomal defects, survival is reasonably good. Regardless, more than half of these pregnancies are often terminated.</p

Comparative Analysis of Prothrombin Complex Concentrate and Fresh Frozen Plasma in the Management of Perioperative Bleeding after Coronary Artery Bypass Grafting

Background and Aim: Recent studies suggested that prothrombin complex concentrate (PCC) might be more effective than fresh frozen plasma (FFP) to reduce red blood cell (RBC) transfusion requirement after cardiac surgery. The benefits and risks associated with the use of PCC over FFP have been investigated in this study including patients undergoing isolated coronary artery bypass grafting(CABG) from a prospective, multicenter registry. Methods: This is a comparative analysis of 416 patients who received postoperatively FFP and 119 patients who received PCC with or without FFP after isolated CABG. Results: Mixed-effects regression analyses adjusted for multiple covariates and participating centers showed that PCC significantly decreased RBC transfusion (67.2% vs. 87.5%, adjusted OR 0.319, 95%CI 0.136-0.752) and platelet transfusion requirements (11.8% vs. 45.2%, adjusted OR 0.238, 95%CI 0.097-0.566) compared with FFP. The PCC cohort received a mean of 2.7\ub13.7 (median, 2.0, IQR 4) units of RBC and the FFP cohort received a mean of 4.9\ub16.3 (median, 3.0, IQR 4) units of RBC (adjusted coefficient, -1.926, 95%CI -3.357-0.494). The use of PCC increased the risk of KDIGO acute kidney injury (41.4% vs. 28.2%, adjusted OR 2.300, 1.203-4.400), but not of KDIGO acute kidney injury stage 3 (6.0% vs. 8.0%, OR 0.850, 95%CI 0.258-2.796) when compared with the FFP cohort. Conclusions: These results suggest that the use of PCC compared with FFP may reduce the need of blood transfusion after CABG. In view of the observational nature of this study, these results shoul

Value of Screening Asymptomatic Carotid Artery Stenosis Prior to Coronary Artery Bypass Grafting: Analysis of the E-CABG Registry

Background and aim: The aim of this study was to evaluate the prognostic impact of asymptomatic carotid artery stenosis(CAS) in patients undergoing isolated coronary artery bypass grafting(CABG). Methods:Patients from the multicenter, prospective E-CABG registry without history of stroke or transient ischemic attack and screened by duplex ultrasound for CAS before isolated CABG were included in this analysis. Results:Among 2813 patients screened by duplex ultrasound for asymptomatic CAS, 11.1% had a CAS of 50-59%, 6.0% of 60-69%, 3.1% of 70-79%, 1.4% of 80-89%, 0.5% of 90-99%, and 1.1% had carotid occlusion. Postoperative stroke occurred in 25 patients(0.9%). Lesions were bilateral in five patients(25%) and ipsilateral to a CAS 6550% in six patients(30%). In univariate analysis, the severity of CAS was associated with a significantly increased risk of stroke(p&lt;0.0001). In multivariate analysis, a CAS of 90-99%(OR 12.03, 95%CI 1.34-108.23) and the presence of an occluded internal carotid artery(OR 8.783, 95%CI 1.820-42.40) were independent predictors of stroke along with urgency of the procedure, severe-massive bleeding according to the E-CABG classification and the presence of a porcelain ascending aorta. Conclusions: Among patients with asymptomatic CAS, the risk of stroke is significant only in patients with a stenosis 6590%. Since this condition has a low prevalence and when left untreated is associated with a relatively low rate of stroke, preoperative screening of asymptomatic CAS before CABG may not be justified. Instead, avoiding manipulation of diseased ascending aorta and prevention of excessive bleeding may be more effective measures to prevent stroke after CABG

No Association Between Ljungan Virus Seropositivity and the Beta-Cell Damaging Process in the Finnish Type 1 Diabetes Prediction and Prevention Study Cohort

BACKGROUND: Ljungan virus (LV) has not confirmed to associate with any human disease, but a possible connection with type 1 diabetes (T1D) has been suggested. Ljungan virus (LV) is a rodent-borne picornavirus that induces a diabetes-like condition in rodents. Approximately 30% of adults and 60% of children are seropositive in Finland. The Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study enabled the use of very well characterized sample panels from children seroconverted to positivity for multiple islet autoantibodies during their prospective observation from birth, in addition samples from age, sex, HLA and residence area matched control children.METHODS: We analyzed LV IgG seroprevalence in 102 case children (65 had also developed T1D), in addition to non-diabetic control children. LV and human parechovirus (HPeV) immunofluorescence assays were used to analyze LV and HPeV specific IgG from 102 plasma samples taken at the time of islet autoantibody appearance, and from 204 samples from the matched control children.RESULTS: Altogether 46.1% of the case and 50.7% of the control children were positive for LV IgG (odds ratio 0.8, 95% CI 0.47-1.36, p=0.416), and 67.6% vs. 79.8% were positive for HPeV IgG, respectively (odds ratio 0.49, 0.27-0.9, p=0.023).CONCLUSIONS: Thus, no risk associations between LV or HPeV -specific IgG, and islet autoimmunity were observed. However, a trend for significantly higher prevalence of HPeV antibodies in control children (p=0.023) suggests a possible protective association of this virus with islet autoimmunity.</p

Meta-Analysis of the Outcome After Postcardiotomy Venoarterial Extracorporeal Membrane Oxygenation in Adult Patients

ObjectiveThis study was planned to pool existing data on outcome and to evaluate the efficacy of postcardiotomy venoarterial extracorporeal membrane oxygenation (VA-ECMO) in adult patients.DesignSystematic review of the literature and meta-analysis.SettingMulti-institutional study.ParticipantsAdult patients with acute heart failure immediately after cardiac surgery.InterventionsVA-ECMO after cardiac surgery. Studies evaluating only heart transplant patients were excluded from this analysis.Measurements and Main ResultsA literature search was performed to identify studies published since 2000. Thirty-one studies reported on 2,986 patients (mean age, 58.1 years) who required postcardiotomy VA-ECMO. The weaning rate from VA-ECMO was 59.5% and hospital survival was 36.1% (95% CI 31.5-40.8). The pooled rate of reoperation for bleeding was 42.9%, major neurological event 11.3%, lower limb ischemia 10.8%, deep sternal wound infection/mediastinitis 14.7%, and renal replacement therapy 47.1%. The pooled mean number of transfused red blood cell units was 17.7 (95% CI 13.3-22.1). The mean stay in the intensive care unit was 13.3 days (95% CI 10.2-16.4). Survivors were significantly younger (mean, 55.7 v 63.6 years, p = 0.015) and their blood lactate level before starting VA-ECMO was lower (mean, 7.7 v 10.7 mmol/L, p = 0.028) than patients who died. One-year survival rate was 30.9% (95% CI 24.3-37.5).ConclusionsPooled data showed that VA-ECMO may salvage one-third of patients unresponsive to any other resuscitative treatment after adult cardiac surgery.</div

Mid-term outcomes of Sapien 3 versus Perimount Magna Ease for treatment of severe aortic stenosis

Background: There is limited information on the longer-term outcome after transcatheter aortic valve replacement (TAVR) with new-generation prostheses compared to surgical aortic valve replacement (SAVR). The aim of this study was to compare the mid-term outcomes after TAVR with Sapien 3 and SAVR with Perimount Magna Ease bioprostheses for severe aortic stenosis.Methods: In a retrospective study, we included patients who underwent transfemoral TAVR with Sapien 3 or SAVR with Perimount Magna Ease bioprosthesis between January 2008 and October 2017 from the nationwide FinnValve registry. Propensity score matching was performed to adjust for differences in the baseline characteristics. The Kaplan-Meir method was used to estimate late mortality.Results: A total of 2000 patients were included (689 in the TAVR cohort and 1311 in the SAVR cohort). Propensity score matching resulted in 308 pairs (STS score, TAVR 3.52.2% vs. SAVR 3.52.8%, p=0.918). In-hospital mortality was 3.6% after SAVR and 1.3% after TAVR (p=0.092). Stroke, acute kidney injury, bleeding and atrial fibrillation were significantly more frequent after SAVR, but higher rate of vascular complications was observed after TAVR. The cumulative incidence of permanent pacemaker implantation at 4years was 13.9% in the TAVR group and 6.9% in the SAVR group (p=0.0004). At 4-years, all-cause mortality was 20.6% for SAVR and 25.9% for TAVR (p=0.910). Four-year rates of coronary revascularization, prosthetic valve endocarditis and repeat aortic valve intervention were similar between matched cohorts.Conclusions: The Sapien 3 bioprosthesis achieves comparable midterm outcomes to a surgical bioprosthesis with proven durability such as the Perimount Magna Ease. However, the Sapien 3 bioprosthesis was associated with better early outcome.Trial registration: ClinicalTrials.gov Identifier: NCT03385915.</div

A protease-based biosensor for the detection of schistosome cercariae

Parasitic diseases affect millions of people worldwide, causing debilitating illnesses and death. Rapid and cost-effective approaches to detect parasites are needed, especially in resource-limited settings. A common signature of parasitic diseases is the release of specific proteases by the parasites at multiple stages during their life cycles. To this end, we engineered several modular Escherichia coli and Bacillus subtilis whole-cell-based biosensors which incorporate an interchangeable protease recognition motif into their designs. Herein, we describe how several of our engineered biosensors have been applied to detect the presence and activity of elastase, an enzyme released by the cercarial larvae stage of Schistosoma mansoni. Collectively, S. mansoni and several other schistosomes are responsible for the infection of an estimated 200 million people worldwide. Since our biosensors are maintained in lyophilised cells, they could be applied for the detection of S. mansoni and other parasites in settings without reliable cold chain access