Mortality After Elective and Ruptured Abdominal Aortic Aneurysm Surgical Repair: 12-Year Single-Center Experience of Estonia.

BACKGROUND AND AIMS: Abdominal aortic aneurysm is a degenerative vascular pathology with high mortality due to its rupture, which is why timely treatment is crucial. The current single-center retrospective study was undertaken to analyze short- and long-term all-cause mortality after operative treatment of abdominal aortic aneurysm and to examine the factors that influence outcome. MATERIAL AND METHODS: The data of all abdominal aortic aneurysm patients treated with open repair or endovascular aneurysm repair in 2004-2015 were retrospectively retrieved from the clinical database of Tartu University Hospital. The primary endpoint was 30-day, 90-day, and 5-year all-cause mortality. The secondary endpoint was determination of the risk factors for mortality. RESULTS AND CONCLUSION: Elective abdominal aortic aneurysm repair was performed on 228 patients (mean age 71.8 years), of whom 178 (78%) were treated with open repair and 50 (22%) with endovascular aneurysm repair. A total of 48 patients with ruptured abdominal aortic aneurysm were treated with open repair (mean age 73.8 years) at the Department of Vascular Surgery, Tartu University Hospital, Estonia. Mean follow-up period was 4.2 ± 3.3 years. In patients with elective abdominal aortic aneurysm, 30-day, 90-day, and 5-year all-cause mortality rates were 0.9%, 2.6%, and 32%, respectively. In multivariate analysis, the main predictors for 5-year mortality were preoperative creatinine value and age (p < 0.05). In patients with ruptured abdominal aortic aneurysm, 30-day, 90-day, and 5-year all-cause mortality rates were 22.9%, 33.3%, and 55.1%, respectively. In multivariate analysis, the risk factors for 30-day mortality in ruptured abdominal aortic aneurysm were perioperative hemoglobin and lactate levels (p < 0.05). According to this study, the all-cause mortality rates of elective abdominal aortic aneurysm and ruptured abdominal aortic aneurysm at our hospital were comparable to those at other centers worldwide. Even though some variables were identified as potential predictors of survival, the mortality rates after ruptured abdominal aortic aneurysm remain high. Early diagnosis, timely treatment, and detection of the risk factors for abdominal aortic aneurysm progression would improve survival in patients with abdominal aortic aneurysm.

Structured education to improve primary-care management of headache: how long do the benefits last? A follow-up observational study.

BACKGROUND AND PURPOSE: Our earlier study showed that structured education of general practitioners (GPs) improved their practice in headache management. Here the duration of this effect was assessed. METHODS: In a follow-up observational study in southern Estonia, subjects were the same six GPs as previously, managing patients presenting with headache as the main complaint. Data reflecting their practice were collected prospectively during a 1-year period commencing 2 years after the educational intervention. The primary outcome measure was referral rate (RR) to neurological services. Comparisons were made with baseline and post-intervention data from the earlier study. RESULTS: In 366 patients consulting during the follow-up period, the RR was 19.9%, lower than at baseline (39.5%; P < 0.0001) or post-intervention (34.7%; P < 0.0001). The RR was diagnosis-dependent: the biggest decline was for migraine. Use of headache diagnostic terms showed changes generally favouring specific terminology. In particular, the proportion of patients given migraine diagnoses greatly increased whilst use of the inappropriate M79.1 (Pericranial) myalgia almost disappeared. Requests for investigations, which had fallen from 26% (of patients seen) at baseline to 4% post-intervention, resurged to 23% (mostly laboratory investigations; requests for X-rays continued to dwindle). Initiation of treatment by the GPs remained at the post-intervention level of just over 80% (up from baseline 58%). CONCLUSIONS: Improvements in GPs' practice after a structured educational programme mostly last for ≥3 years, some showing further betterment. A few measures suggest the beginnings of a decline towards baseline levels. This policy-informing evidence for continuing medical education indicates that the educational programme needs repeating every 2-3 years.

Whole-exome sequencing identifies a potential TTN mutation in a multiplex family with inguinal hernia.

PURPOSE: Inguinal hernia repair is one of the most common procedures in general surgery. Males are seven times more likely than females to develop a hernia and have a 27 % lifetime 'risk' of inguinal hernia repair. Several studies have demonstrated that a positive family history is an important risk factor for the development of primary inguinal hernia, which indicates that genetic factors may play important roles in the etiology of the disease. So far, the contribution of genetic factors and underlying mechanisms for inguinal hernia remain largely unknown. The aim of this study was to investigate a multiplex Estonian family with inguinal hernia across four generations. METHODS: The whole-exome sequencing was carried out in three affected family members and subsequent mutation screening using Sanger sequencing was performed in ten family members (six affected and four unaffected). RESULTS: Whole-exome sequencing in three affected family members revealed a heterozygous missense mutation c.88880A>C (p.Lys29627Thr; RefSeq NM_001256850.1) in the highly conserved myosin-binding A-band of the TTN gene. Sanger sequencing demonstrated that this mutation cosegregated with the disease in this family and was not present in ethnically matched control subjects. CONCLUSION: We report that missense variant in the A-band of TTN is the strongest candidate mutation for autosomal-dominant inguinal hernia with incomplete penetrance.

Copy number variation analysis detects novel candidate genes involved in follicular growth and oocyte maturation in a cohort of premature ovarian failure cases.

STUDY QUESTION: Can spontaneous premature ovarian failure (POF) patients derived from population-based biobanks reveal the association between copy number variations (CNVs) and POF? SUMMARY ANSWER: CNVs can hamper the functional capacity of ovaries by disrupting key genes and pathways essential for proper ovarian function. WHAT IS KNOWN ALREADY: POF is defined as the cessation of ovarian function before the age of 40 years. POF is a major reason for female infertility, although its cause remains largely unknown. STUDY DESIGN, SIZE, DURATION: The current retrospective CNV study included 301 spontaneous POF patients and 3188 control individuals registered between 2003 and 2014 at Estonian Genome Center at the University of Tartu (EGCUT) biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: DNA samples from 301 spontaneous POF patients were genotyped by Illumina HumanCoreExome (258 samples) and HumanOmniExpress (43 samples) BeadChip arrays. Genotype and phenotype information was drawn from the EGCUT for the 3188 control population samples, previously genotyped with HumanCNV370 and HumanOmniExpress BeadChip arrays. All identified CNVs were subjected to functional enrichment studies for highlighting the POF pathogenesis. Real-time quantitative PCR was used to validate a subset of CNVs. Whole-exome sequencing was performed on six patients carrying hemizygous deletions that encompass genes essential for meiosis or folliculogenesis. MAIN RESULTS AND THE ROLE OF CHANCE: Eleven novel microdeletions and microduplications that encompass genes relevant to POF were identified. For example, FMN2 (1q43) and SGOL2 (2q33.1) are essential for meiotic progression, while TBP (6q27), SCARB1 (12q24.31), BNC1 (15q25) and ARFGAP3 (22q13.2) are involved in follicular growth and oocyte maturation. The importance of recently discovered hemizygous microdeletions of meiotic genes SYCE1 (10q26.3) and CPEB1 (15q25.2) in POF patients was also corroborated. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis and no functional studies were performed. Anamnestic data obtained from population-based biobank lacked clinical, biological (hormone levels) or ultrasonographical data, and spontaneous POF was predicted retrospectively by excluding known extraovarian causes for premature menopause. WIDER IMPLICATIONS OF THE FINDINGS: The present study, with high number of spontaneous POF cases, provides novel data on associations between the genomic aberrations and premature menopause of ovarian cause and demonstrates that population-based biobanks are powerful source of biological samples and clinical data to reveal novel genetic lesions associated with human reproductive health and disease, including POF. STUDY FUNDING/COMPETING INTEREST: This study was supported by the Estonian Ministry of Education and Research (IUT20-43, IUT20-60, IUT34-16, SF0180027s10 and 9205), Enterprise Estonia (EU30020 and EU48695), Eureka's EUROSTARS programme (NOTED, EU41564), grants from European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways (IAPP, SARM, |EU324509) and Horizon 2020 innovation programme (WIDENLIFE, 692065), Academy of Finland and the Sigrid Juselius Foundation.

A missense mutation in DUSP6 is associated with Class III malocclusion.

Class III malocclusion is a common dentofacial phenotype with a variable prevalence according to ethnic background. The etiology of Class III malocclusion has been attributed mainly to interactions between susceptibility genes and environmental factors during the morphogenesis of the mandible and maxilla. Class III malocclusion shows familial recurrence, and family-based studies support a predominance of an autosomal-dominant mode of inheritance. We performed whole-exome sequencing on five siblings from an Estonian family affected by Class III malocclusion. We identified a rare heterozygous missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene, a likely causal variant. This variant co-segregated with the disease following an autosomal-dominant mode of inheritance with incomplete penetrance. Transcriptional activation of DUSP6 has been presumed to be regulated by FGF/FGFR and MAPK/ERK signaling during fundamental processes at early stages of skeletal development. Several candidate genes within a linkage region on chromosome 12q22-q23--harboring DUSP6--are implicated in the regulation of maxillary or mandibular growth. The current study reinforces that the 12q22-q23 region is biologically relevant to craniofacial development and may be genetically linked to the Class III malocclusion.

Non-syndromic tooth agenesis associated with a nonsense mutation in ectodysplasin-A (EDA).

Mutations in the ectodysplasin-A (EDA) gene have been generally associated with X-linked hypohidrotic ectodermal dysplasia (XLHED). Recently, missense mutations in EDA have been reported to cause familial non-syndromic tooth agenesis. In this study, we report a novel EDA mutation in an Estonian family segregating non-syndromic tooth agenesis with variable expressivity. Affected individuals had no associated defects in other ectodermal organs. Using whole-exome sequencing, we identified a heterozygous nonsense mutation c.874G>T (p.Glu292X) in the TNF homology domain of EDA in all affected female patients. This protein-altering variant arose de novo, and the potentially causative allele was transmitted to affected offspring from the affected mother. We suggest that the dental phenotype variability described in heterozygous female carriers of EDA mutation may occur because of the differential pattern of X-chromosome inactivation, which retains reduced levels of EDA-receptor signaling in tissues involved in tooth morphogenesis. This results in selective tooth agenesis rather than XLHED phenotype. The present study broadens the mutation spectrum for this locus and demonstrates that EDA mutations may result in non-syndromic tooth agenesis in heterozygous females.

Risk for Heterosexual HIV Transmission Among Non-Injecting Female Partners of Injection Drug Users in Estonia.

The HIV epidemic in Estonia, as with other eastern European countries, is currently concentrated among injection drug users (IDUs). Non-IDUs who have IDU sex partners could serve as a potential bridge in an expanding epidemic. We applied HIV transmission modelling to data collected from non-IDU/IDU heterosexual couples in Kohtla-Järve, Estonia to estimate HIV risk from IDUs to their sex partners based on self-reported sexual behaviors shared by the couple. IDUs and their current main non-injecting sex partners were recruited for an interviewer-administered survey and HIV testing. Bernoulli modelling techniques were applied to estimate the risk of HIV transmission (incidence) among HIV negative non-injecting female partners of male IDUs. The estimated HIV incidence in this population of non-injecting women with only main sexual partners in the last 6 months ranged from 3.24 to 4.94 HIV seroconversions per 100 person years depending on the value used in the models for the per act transmission rate during acute stage infection. Non-IDUs who have IDU sex partners are at high risk for HIV and could serve as a potential bridge to a more generalized epidemic. Whether this might lead to an expansion of the HIV epidemic beyond core groups in Estonia or other Eastern European countries warrants closer study.

Ten years experience of treating aorto-femoral bypass graft infection with venous allografts.

OBJECTIVE: The aim of the present study was to analyze our results of treating synthetic vascular graft infection in the aorto-femoral segment with venous allografts. PATIENTS AND METHODS: During 1997-2006 we treated 11 male patients with venous allografts for aorto-femoral segment prosthetic graft infection. Patients were followed postoperatively with patency assessment based on Doppler ultrasonography. RESULTS: The mean interval between the implantation of the synthetic vascular graft and the appearance of infection was 43+/-29 months (range 5 months-10 years). Overall primary patency of the venous allograft was 100%, 88% and 66% at 1, 6 and 36 months, respectively. Secondary patency rates of the venous allograft were 94% and 73% after 5 and 8 years, respectively. Overall survival rate was 100%, 64%, 46% and 27% after one month, 3, 5 and 8 years, respectively. Limb salvage rate was 100%, 94% and 73% after 1 month, 5 and 8 years, respectively. CONCLUSIONS: The use of in situ venous allograft for the treatment of synthetic graft infection in the aorto-femoral segment has led to favourable short- and long-term results.

Clear differences in adiponectin level and glutathione redox status revealed in obese and normal-weight patients with psoriasis.

BACKGROUND: Several studies have shown increased prevalence of obesity in patients with psoriasis. OBJECTIVES: To characterize both inflammatory- and oxidative stress-related differences between obese patients with psoriasis (OPP) and normal-weight patients with psoriasis (NWPP). METHODS: The plasma concentrations of adiponectin and interleukin (IL)-6 were analysed by quantitative sandwich enzyme immunoassay technique in 10 patients with a body mass index (BMI)<25 and 12 patients with a BMI>30. Total glutathione and oxidized glutathione levels were measured spectrophotometrically. RESULTS: Plasma concentration of adiponectin in NWPP was more than twice the level in healthy normal-weight controls (P<0.001), while such an elevation did not occur in OPP. OPP were characterized by a significantly increased IL-6 level, which correlated negatively with the adiponectin level (r=-0.85, P<0.001). The glutathione redox status, which was also inversely correlated with the adiponectin level (r=-0.63, P<0.05), was associated with significantly increased oxidative stress in the OPP compared with the NWPP or controls. CONCLUSIONS: Obesity in patients with psoriasis is associated with both decreased plasma levels of protective adiponectin compared with NWPP, and enhanced systemic inflammation and oxidative stress. These findings are in concordance with high prevalence of diseases related to lower adiponectin levels among psoriasis patients.

The prevalence of chlamydial infection in Estonia: a population-based survey.

The aim of this study was to estimate the prevalence of Chlamydia trachomatis infection among Estonian men and women by a cross-sectional study based on the screening of a probability sample of the residents of Tartu using participant-collected, mail-delivered testing for C. trachomatis complemented with the self-administered questionnaire. Full participation as defined by returning both the questionnaire and specimen was 34% (n = 479; 95% confidence interval [CI] 32-37%). Study participation was 40% (n = 560; 95% CI 37-43%) for subjects returning either or both the study questionnaire and specimen. After weighing the population distribution, the prevalence estimate for the age group of 18-35 years was 5.4% (95% CI 3.0-7.5%), 6.9% (95% CI 3.6-10.3%) among women and 2.7% (95% CI 0.3-5.0%) among men. The number of sexual partners in the past 12 months was the strongest predictor of infection.

Arterial elasticity is associated with endothelial vasodilatory function and asymmetric dimethylarginine level in healthy subjects.

Arterial stiffening may be linked to the reduced bioactivity of nitric oxide (NO) and increased plasma concentrations of the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA). The aim of this study was to investigate whether large (C1) and small artery (C2) elasticity is associated with endothelial function index (EFI) and plasma concentration of ADMA. We included 63 healthy subjects, aged 19 to 70 years, in the study. EFI, C1 and C2 were assessed by pulse wave analysis (PWA) and ADMA level was measured using an enzyme-linked immunoassay. Linear regression analysis revealed significant positive correlation between EFI and both C1 and C2 (R = 0.29, p = 0.02; R = 0.38, p = 0.002, respectively). A significant inverse association occurred between ADMA and C1 as well as C2 (R = -0.32, p = 0.03; R = -0.37, p = 0.009, respectively). In multiple regression analysis, C2 was determined by EFI, ADMA, age and BMI, and C1 was correlated with EFI, age and BMI. These findings suggest that endothelial vasodilatory dysfunction and accumulation of ADMA may be important mechanisms underlying reduced arterial elasticity in healthy subjects.