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Psychosocial and biological factors influence the perception of physical changes during pregnancy. Some pregnant women present to the obstetric emergency department (ED) with diverse symptoms not requiring urgent medical action. These visits result in over-consultation, tying up resources and inflating health care expenses. This study outlines factors associated with multiple ED visits during pregnancy, measures the prevalence of anxiety and depression, and explores the choice of maternity clinic for delivery aiming to elucidate options for care strategies. This prospective, cross-sectional, questionnaire-based bicentric study was performed in the obstetric outpatient departments of two university hospitals in Germany and recruited pregnant women between 12/2016 and 11/2017. The questionnaire included socio-demographics, obstetric history, anxiety (GAD-7), depression (PHQ-9), and health status (WHO-5, SF-12). This analysis included 496 women and showed that women with numerous ED visits were significantly younger (p

Background: The P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD. Methods: Fifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies. Results: We identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci ( TTN , CAND2 , SCN10A , PITX2 , CAV1 , SYNPO2L , SOX5 , TBX5, MYH6, RPL3L ). The top variants at known sarcomere genes ( TTN, MYH6 ) were associated with longer PWD and increased AF risk. However, top variants at other loci (eg, PITX2 and SCN10A ) were associated with longer PWD but lower AF risk. Conclusions: Our results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.

Background DNA methylation is a key epigenetic modification that can directly affect gene regulation. DNA methylation is highly influenced by environmental factors such as cigarette smoking, which is causally related to chronic obstructive pulmonary disease (COPD) and lung cancer. To date, there have been few large-scale, combined analyses of DNA methylation and gene expression and their interrelations with lung diseases. Results We performed an epigenome-wide association study of whole blood gene expression in ~ 6000 individuals from four cohorts. We discovered and replicated numerous CpGs associated with the expression of cis genes within 500 kb of each CpG, with 148 to 1,741 cis CpG-transcript pairs identified across cohorts. We found that the closer a CpG resided to a transcription start site, the larger its effect size, and that 36% of cis CpG-transcript pairs share the same causal genetic variant. Mendelian randomization analyses revealed that hypomethylation and lower expression of CHRNA5, which encodes a smoking-related nicotinic receptor, are causally linked to increased risk of COPD and lung cancer. This putatively causal relationship was further validated in lung tissue data. Conclusions Our results provide a large and comprehensive association study of whole blood DNA methylation with gene expression. Expression platform differences rather than population differences are critical to the replication of cis CpG-transcript pairs. The low reproducibility of trans CpG-transcript pairs suggests that DNA methylation regulates nearby rather than remote gene expression. The putatively causal roles of methylation and expression of CHRNA5 in relation to COPD and lung cancer provide evidence for a mechanistic link between patterns of smoking-related epigenetic variation and lung diseases, and highlight potential therapeutic targets for lung diseases and smoking cessation.

Publisher's version (útgefin grein), The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease., We provide all investigator and study-specific acknowledgements in Supplementary Note 1, and funding sources in Supplementary Note 2.

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality1,2. We performed multi-ancestry (N=293,051) and European only (N=271,570) genome-wide association (GWAS) meta-analyses for the PR interval, discovering 210 loci of which 149 are novel. Variants at all loci nearly doubled the percentage of heritability explained, from 33.5% to 62.6%. We observed enrichment for genes involved in cardiac muscle development/contraction and the cytoskeleton highlighting key regulation processes for atrioventricular conduction. Additionally, 19 novel loci harbour genes underlying inherited monogenic heart diseases suggesting the role of these genes in cardiovascular pathology in the general population. We showed that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease risk, including distal conduction disease, AF, atrioventricular pre-excitation, non-ischemic cardiomyopathy, and coronary heart disease. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.

Purpose: Reduction of maternal morbidity and mortality is a major worldwide objective anchored in the millennium goals of the United Nations. To improve fetal and maternal care, a constant attempt to discover groundbreaking technologies is ongoing. One approach is the enhancement of non-invasive fetal ECG devices. Most importantly, acceptance of new technologies by pregnant women is a prerequisite for successful implementation. Methods: This questionnaire-based study conducted at the University Hospital Heidelberg, Germany between May and June 2017 evaluates pregnant women’s attitudes towards a new device for fetal ECG monitoring and its potential home usage. The study population was questioned after exposure to the Parides/Atlantis prototype (Nemo Healthcare, Veldhoven, The Netherlands), whereas the maternal and gestational age-matched control group was left to envision telemedical topics. Results: The prototype and its potential usage in a clinical and telemedical setting was highly accepted, and its comfort and appearance satisfied participants. Its use caused significantly improved telemedical understanding as envision increased (p = 0.0015). Implementation and integration of telemedical devices into antenatal care was significantly preferred by the study group (p = 0.0011), though participants desire more specific features for their personal use. Optional home-based self-monitoring to reduce scheduled doctoral visits (p = 0.0004) as well as self-assessment prior to self-initiated, unscheduled consultation (p < 0.0001) could be affected positively by such a device. Furthermore, it could reduce face-to-face interaction with the care provider (p = 0.0163). Conclusions: The positive feedback on remote self-monitoring might open options for a more “patient as partners” oriented prenatal care in the future. Safety and reliability remain a major issue. More comprehensive studies with new technologies are needed to diligently ensure quality of care. Finally, results for new technologies must be communicated to pregnant women for their acceptance and usage of new devices.

BackgroundThe demand for fetal monitoring and constant reassurance is high in pregnant women. Consequently, pregnant women use various health apps and are more likely to visit emergency departments due to subjective but nonurgent complaints. However, electronic health (eHealth) and mobile health (mHealth) solutions are rarely used to prevent nonurgent emergency consultations. To implement modern care solutions, a better understanding of the attitudes, fears, and hopes of health care professionals toward eHealth and mHealth is needed. ObjectiveThe aim of this study was to investigate the attitudes of health care professionals in obstetrics toward telemedicine. MethodsA quantitative Web-based survey on health care professionals in obstetrics in Germany was conducted. The participants included nurses, midwives, and physicians of all age groups and job positions working in hospitals that provide various levels of health care. The questionnaire comprised 24 questions about the characteristics of the study population, views about emergency consultations in obstetrics, attitude toward telemedicine, job satisfaction, and sleeping behavior. ResultsIn total, 244 health care professionals participated in the Web-based survey. In general, health care professionals were skeptical (170/233, 72.9%) about the use of telemedicine in obstetrics; however, 55.8% (130/233) recognized its potential. Moreover, 72% (62/86) of physicians were optimistic in using apps for pregnancy monitoring, whereas 36.1% (47/130) of nonphysicians (P

Background: We developed a novel electrocardiographic marker, T-wave area dispersion (TW-Ad), which measures repolarization heterogeneity by assessing interlead T-wave areas during a single cardiac cycle and tested whether it can identify patients at risk for sudden cardiac death (SCD) in the general population. Methods and Results: TW-Ad was measured from standard digital 12-lead ECG in 5618 adults (46% men; age, 50.9±12.5 years) participating in the Health 2000 Study—an epidemiological survey representative of the Finnish adult population. Independent replication was performed in 3831 participants of the KORA S4 Study (Cooperative Health Research in the Region of Augsburg; 49% men; age, 48.7±13.7 years; mean follow-up, 8.8±1.1 years). During follow-up (7.7±1.4 years), 72 SCDs occurred in the Health 2000 Survey. Lower TW-Ad was univariately associated with SCD (0.32±0.36 versus 0.60±0.19; P P P P P Conclusion: Low TW-Ad, reflecting increased heterogeneity of repolarization, in standard 12-lead resting ECGs is a powerful and independent predictor of SCD in the adult general population.

The pro-inflammatory cytokine interleukin (IL)-1β is implicated in the development of insulin resistance and beta-cell dysfunction, whereas higher circulating IL-1 receptor antagonist (IL-1RA - an endogenous inhibitor of IL-1β - has been suggested to improve glycemia and beta-cell function in patients with type 2 diabetes. In order to elucidate the protective role of IL-1RA, this study aimed to identify genetic determinants of circulating IL-1RA concentration and to investigate their associations with immunological and metabolic variables related to cardiometabolic risk. In the analysis of 7 discovery and 4 replication cohort studies, two single nucleotide polymorphisms (SNPs) were independently associated with circulating IL-1RA concentration (rs4251961 at the IL-1RN locus, n=13,955, P=2.76x10(-21); and rs6759676, closest gene locus IL1F10, n=13,994, P=1.73x10(-17)). The proportion of the variance in IL-1RA explained by both SNPs combined was 2.0%. IL-1RA-raising alleles of both SNPs were associated with lower circulating C-reactive protein concentration. The IL-1RA-raising allele of rs6759676 was also associated with lower fasting insulin and lower homeostasis model assessment insulin resistance (HOMA-IR). In conclusion, we show that circulating IL-1RA levels are predicted by two independent SNPs at the IL-1RN and IL-1F10 loci and that genetically raised IL-1RA may be protective against the development of insulin resistance.

Allergen-specific immunoglobulin E (present in allergic sensitization) has a central role in the pathogenesis of allergic disease. We performed the first large-scale genome-wide association study (GWAS) of allergic sensitization in 5,789 affected individuals and 10,056 controls and followed up the top SNP at each of 26 loci in 6,114 affected individuals and 9,920 controls. We increased the number of susceptibility loci with genome-wide significant association with allergic sensitization from three to ten, including SNPs in or near TLR6, C11orf30, STAT6, SLC25A46, HLA-DQB1, IL1RL1, LPP, MYC, IL2 and HLA-B. All the top SNPs were associated with allergic symptoms in an independent study. Risk-associated variants at these ten loci were estimated to account for at least 25% of allergic sensitization and allergic rhinitis. Understanding the molecular mechanisms underlying these associations may provide new insights into the etiology of allergic disease.

Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina Human Methylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2×10-5 and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2×10-5 and 3.0×10-3). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-Hadjusted p-value = 1.5×10-9). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes-related traits are associated and that these associations are partially BMI-dependent. Furthermore, the interaction of ABCG1 with glucose metabolism is modulated by epigenetic processes.

BACKGROUND When a small gestational sac with no visible embryo is seen at an early pregnancy ultrasound scan, the clinician cannot distinguish a viable from a non-viable pregnancy. A test for the prediction of early pregnancy viability at the initial visit was developed in 2003. Maternal age, gestational sac diameter (GSD) and serum progesterone levels were used in a logistic regression model to create an algorithm for estimation of the probability of a viable pregnancy. The objective of this study was to assess how well the test performed in routine clinical practice. METHODS This is a retrospective observational study of women who had the test performed in our Early Pregnancy Unit over a 6-year period. Inclusion criteria were a spontaneous conception, gestational sac of

Aim: To investigate the efficacy of a combined intravitreal therapy with prior photodynamic therapy (PDT) in patients with wet age-related macular degeneration. Methods: Fifty-two patients (mean age: 72.7 years) with predominantly classic choroidal neovascularization received low-fluence PDT (42 J/cm2 for 72 s), followed 24 h later by a 0.4-ml core pars plana vitrectomy with intravitreal injection of dexamethasone (0.8 mg) and bevacizumab (1.25 mg). The best-corrected visual acuity (BCVA; 6 m Snellen), central macular thickness (optical coherence tomography), intraocular pressure and the need for retreatment were assessed. Results: BCVA changed significantly (vs. baseline) at 3 months (+0.11), 9 months (+0.19) and 14 months (+0.16). At the end of the follow-up period, BCVA had improved by >0.1 in the majority of the patients (72.9%), and the mean central retinal thickness had decreased by –44.3% (–211 µm). The retreatment rate was 25%. No increase in intraocular pressure or other adverse event was reported. Conclusions: The pharmacological effects of the drugs, the low-fluence PDT, and the physiological effects of the therapy may have contributed to the sustainability of the therapeutic benefits.

Importance Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures Circulating TNF-α concentration. Main Outcomes and Measures DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (β [SE] = −0.01 [0.003]; P = 7.36 × 10 −8 ), cg08122652 (β [SE] = −0.008 [0.002]; P = 2.24 × 10 −7 ), and cg22930808(β [SE] = −0.01 [0.002]; P = 6.92 × 10 −8 ); NLRC5 at cg16411857 (β [SE] = −0.01 [0.002]; P = 2.14 × 10 −13 ) and cg07839457 (β [SE] = −0.02 [0.003]; P = 6.31 × 10 −10 ); or ABO , at cg13683939 (β [SE] = 0.04 [0.008]; P = 1.42 × 10 −7 ) and cg24267699 (β [SE] = −0.009 [0.002]; P = 1.67 × 10 −7 ), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α–linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10 −5 ; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10 −5 ). Conclusions and Relevance We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Socio-economic and individual lifestyle features associated with the nutritional state were examined in 7-9-year-old children of lower and lower middle-class families living under the international poverty line. Mild and moderate undernutrition was frequent but overweight also occurred.Three groups of sex- and age-matched randomly selected children from the Kolkata Child Nutrition Study (data collection between April and November 2001) attending public primary schools of North Kolkata participated (42 children of low body mass index (BMI12 kg/m(2),=LBMI), 100 children of intermediate BMI (14-16 kg/m(2); IBMI) and 51 children of high BMI (16 kg/m(2); HBMI). Individual and social characteristics of the three BMI categories were assessed using a structured interview of their families.Families of LBMI children owned more TV (83.3% versus 60%; p-value: 0.007) and spent less money for rice (80.4% versus 52.5% of the families spent less than 11 Indian rupees (INR) for rice/day, p0.003) when compared to families of IBMI children while income of the families of the 2 groups was similar. The families of HBMI children had more income per head per day (62.5% versus 32% earned more than 19 INR/head/day, p0.02).Lifestyle and socio-economic differences in families are associated with distinct variations in body weight of their children in a population living in a low income area in Kolkata. Various degrees of poverty may lead to a propensity to develop both, underweight and modest overweight.

Background Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. Methods Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. Results Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). Conclusions Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D. Electronic supplementary material The online version of this article (doi:10.1186/s12920-015-0141-x) contains supplementary material, which is available to authorized users.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimoto's thyroiditis), as well as autoimmune hyperthyroidism (Graves' disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P, Author Summary Individuals with thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune thyroid diseases (AITD), which are common in the general population and associated with increased cardiovascular, metabolic and psychiatric morbidity and mortality. As the causative genes of TPOAbs and AITD remain largely unknown, we performed a genome-wide scan for TPOAbs in 18,297 individuals, with replication in 8,990 individuals. Significant associations were detected with variants at TPO, ATXN2, BACH2, MAGI3, and KALRN. Individuals carrying multiple risk variants also had a higher risk of increased thyroid-stimulating hormone levels (including subclinical and overt hypothyroidism), and a decreased risk of goiter. The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, and the MAGI3 variant was also associated with an increased risk of hypothyroidism. This first genome-wide scan for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. These results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which individuals are particularly at risk of developing clinical thyroid dysfunction.

Purpose To investigate the clinical efficacy and safety of an additional core vitrectomy to the standard therapy in patients with exudative age-related macular degeneration (ARMD). Methods In this prospective, controlled, single-centre study, 50 eyes of 50 patients (mean age: 74.1 ± 7.1; median 74 (69/78)) with ARMD were enrolled and randomized 1:1 to group 1 – core vitrectomy additional to three times injections of ranibizumab (3x Rbz) and Group 2 – 3x Rbz (control). 1 16 of 25 eyes in Group 1(64%) and 12 of 25 (48%) in Group 2 had a posterior vitreous detachment (PVD) prior to start of the study. Changes in best-corrected visual acuity (BCVA) using ETDRS charts, central macular thickness and macular volume (OCT) as well as the rate of reinjection with an OCT-based pro renata (PRN) protocol were monitored prospectively over 48 weeks. Forty-seven eyes completed follow-up at week 48. Results In Group 1, 4 of 24 lost 1 line of BCVA (16.7%) and 3 of 24 lost 2 lines (12.5%), whereas 17 of 24 gained more than 1 line (70.8%) and improved in average by 9.8 letters. In Group 2, 3 of 23 remained stable and 20 of 23 gained more than or exactly 1 line (78.3%), resulting in 14.3 letters, with no loss of lines. Central macular thickness decreased by 85.58 μm (28.8%) in Group 1 and by 121.43 μm (32.68%) in Group 2 compared with baseline. In Group 1, four patients received three additional and two patients, two additional Rbz injections. In Group 2, three patients received three additional, three patients two and 12 patients one additional Rbz injections. This yielded in an average injection rate of 3.66 in Group 1 and 4.17 in Group 2 over 48 weeks. Posterior vitreous detachment (PVD) was identified in Group 1 in 16 of 24 (66.7%) and in Group 2 in 12 of 23 (52.2%) patients at baseline. At week 48, 6 of 8 (75%) of the patients in Group 1 with initial attached vitreous showed a vitreal detachment, whereas only 1 of 11 (9%) in Group 2 had a new occurred detachment of the vitreous. No systemic or ocular adverse events were noticed. Conclusion An initial core vitrectomy combined with a conventional ranibizumab injection regimen for exudative AMD patients was safe and lead to similar functional results with less intravitreal ranibizumab injections over 48 weeks.

The objective of the present study was the evaluation of MRI of the breast in the follow-up of patients who had undergone autogenous tissue breast reconstruction using either a latissimus-dorsi muscle flap or a transverse rectus abdominis myocutaneous (TRAM) flap as correlated with patients' clinical, conventional mammographic and sonographic findings. Included in the study were 41 patients. The MRI consisted of T2-weighted turbo spin-echo (TSE) sequences and dynamic measurements pre- and postcontrast using T1-weighted gradient-echo (GE) sequence. The following factors were evaluated: recognition of the flap; evidence of edema; skin thickening; and focally increased contrast medium uptake. Contrast medium dynamics were documented in instances of increased focal uptake. Flaps could be distinguished from surrounding residual breast tissue in all cases. Edema and skin thickening in the residual mammary tissue and flap implant were observed in 72.7% of patients undergoing radiation, but in only 15.8% of those not undergoing radiotherapy. The MRI excluded disease recurrence in 4 patients with suspicious mammographic and/or sonographic findings. One instance of multifocal disease recurrence identified at MRI evaded detection with all other imaging techniques used. The MRI returned false-positive findings in three cases. Because of their configuration and contrast medium uptake dynamics and their location immediately adjacent to the contact zone between the flap implant and residual mammary tissue, these findings were impossible to differentiate from a recurrent carcinoma. The MRI of the breast is generally suitable for follow-up examination of autogenous tissue reconstructions. Problems may be encountered in the evaluation of the contact zone between local adipose tissue and the flap leading to false-positive results.