The effect of denosumab on disseminated tumor cells (DTCs) of breast cancer patients with neoadjuvant treatment: a GeparX translational substudy.

Background: Disseminated tumor cells (DTCs) in the bone marrow are observed in about 40% at primary diagnosis of breast cancer and predict poor survival. While anti-resorptive therapy with bisphosphonates was shown to eradicate minimal residue disease in the bone marrow, the effect of denosumab on DTCs, particularly in the neoadjuvant setting, is largely unknown. The recent GeparX clinical trial reported that denosumab, applied as an add-on treatment to nab-paclitaxel based neoadjuvant chemotherapy (NACT), did not improve the patient's pathologic complete response (pCR) rate.

A frozen decade: Ten years outcome of atrial fibrillation ablation using a single shot device for pulmonary vein isolation.

Aims: Cryoballoon-guided pulmonary vein isolation (CB-PVI) for symptomatic atrial fibrillation (AF) has become an established treatment option with encouraging results in terms of safety and efficacy. Data reporting on long-term data beyond a follow-up (FU) period of 5 years is scarce. This prospective study aimed to evaluate very long-term outcome after CB-PVI for AF.

[Psychiatric comorbidities in hidradenitis suppurativa/acne inversa].

Background: The findings of most studies suggest that depression and anxiety disorders are the most common psychiatric comorbidities in patients with hidradenitis suppurativa/acne inversa (HS/AI).

Methods: In a prospective study, 51 patients with HS/AI were further examined for psychiatric comorbidity using a standardized interview and questionnaires.

Results: In psychiatric examination, 29.

Cool enough? Lessons learned from cryoballoon-guided catheter ablation for atrial fibrillation in young adults.

Introduction: Cryoballoon (CB)-guided ablation of atrial fibrillation (AF) is established in symptomatic AF patients. This study sought to determine the safety and efficacy of CB pulmonary vein isolation (PVI) in young adults.

Methods And Results: A total of 93 consecutive patients aged <45 years referred to our center for AF ablation were included in this observational study.

Increased expression profile of NCSTN, Notch and PI3K/AKT3 in hidradenitis suppurativa.

Background: In a small number of kindreds with familial hidradenitis suppurativa (HS) different mutations of NCSTN (nicastrin) have been identified. Blocking of NCSTN leads to impairment of the Notch and PI3K/AKT signalling pathway, which is assumed to play a pathogenic role in HS. However, very limited data are available concerning expression levels of these pathway components in HS skin.

[Hidradenitis suppurativa/acne inversa in the genitoanal region].

Hidradenitis suppurativa/acne inversa (HS/AI) is a chronic inflammatory skin disease. Several studies showed that perianal, perineal and gluteal involvement is more common in men. Axillary, submammary and inguinal localizations seem to be more prevalent in women.

Interventional techniques to increase implantation success of transvenous phrenic nerve stimulation for central sleep apnea treatment.

Purpose: Central sleep apnea (CSA) is a highly common comorbidity in heart failure (HF) patients and is known to deteriorate quality of life and prognosis. Effective treatment options are scarce. Transvenous phrenic nerve stimulation (PNS) has been shown to be effective and safe in CSA treatment in HF.

Operative results, sexual function and quality of life after gracilis muscle transposition in complex rectovaginal fistulas.

Aim: Successful treatment of complex rectovaginal fistulas (RVFs) continues to be a surgical challenge. Interposition of well-perfused tissue, such as gracilis muscle, is one treatment option. The aim of this study was to investigate the operative results, sexual function and quality of life after gracilis muscle transposition (GMT) in the authors' own group of patients.

Benchmarking of a checklist for the identification of familial risk for breast and ovarian cancers in a prospective cohort.

The detection of deleterious germline mutations in BRCA1 and BRCA2 considerably influences the clinical management of healthy and diseased carriers. Therefore, the identification of persons at risk who could uptake genetic counseling and testing is pivotal. We developed a checklist with validated criteria to improve the identification, and prospectively evaluate the incidence, of familial cancer history in 5091 breast cancer patients.

Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement.

Background Long-term data on evolution and clinical impact of myocardial fibrosis in valvular heart disease are scarce. Methods and Results In this 10 years' extension of a prospective study in patients undergoing conventional aortic valve replacement because of symptomatic severe aortic valve stenosis, the impact of myocardial replacement fibrosis (MRF) on long-term outcome was assessed. Endomyocardial biopsies were acquired during aortic valve replacement in 58 consecutive patients.

Clinical impact of the alpha-galactosidase A gene single nucleotide polymorphism -10C>T: A single-center observational study.

Single nucleotide polymorphisms (SNPs) in the alpha-galactosidase A gene region (GLA) have been discussed as potential cause of symptoms and organ manifestations similarly to those seen in Fabry disease (FD). However, due to scarce data, clinical implications remain limited. The aim of the present study was to investigate the clinical impact of -10C>T SNP in the GLA.

Fabry disease revisited: Management and treatment recommendations for adult patients.

Fabry disease is an X-linked lysosomal storage disorder caused by mutations in the GLA gene leading to deficient α-galactosidase A activity, glycosphingolipid accumulation, and life-threatening complications. Phenotypes vary from the "classic" phenotype, with pediatric onset and multi-organ involvement, to later-onset, a predominantly cardiac phenotype. Manifestations are diverse in female patients in part due to variations in residual enzyme activity and X chromosome inactivation patterns.

Adaptive servo-ventilation for central sleep apnoea in systolic heart failure: results of the major substudy of SERVE-HF.

Aims: The SERVE-HF trial investigated the impact of treating central sleep apnoea (CSA) with adaptive servo-ventilation (ASV) in patients with systolic heart failure. A preplanned substudy was conducted to provide insight into mechanistic changes underlying the observed effects of ASV, including assessment of changes in left ventricular function, ventricular remodelling, and cardiac, renal and inflammatory biomarkers.

Methods And Results: In a subset of the 1325 randomised patients, echocardiography, cardiac magnetic resonance imaging (cMRI) and biomarker analysis were performed at baseline, and 3 and 12 months.

Fabry disease under enzyme replacement therapy-new insights in efficacy of different dosages.

Background: Fabry patients on reduced dose of agalsidase-beta or after switch to agalsidase-alfa show a decline in estimated glomerular filtration rate (eGFR) and an increase of the Mainz Severity Score Index.

Methods: In this prospective observational study, we assessed end-organ damage and clinical symptoms in 112 patients who had received agalsidase-beta (1.0 mg/kg) for >1 year, who were (i) non-randomly assigned to continue this treatment regime (regular-dose group, n = 37); (ii) received a reduced dose of agalsidase-beta and subsequent switch to agalsidase-alfa (0.

[Prophylactic Appendectomy: Yes or No?].

At more than 50%, appendicitis is the leading cause of acute intra-abdominal disease requiring surgery. In the course of various other operations, prophylactic appendectomy (PA) is frequently performed. This study examines to what extent PA is justified.

Extent of size, shape and systolic variability of the left ventricular outflow tract in aortic stenosis determined by phase-contrast MRI.

Purpose: Left ventricular outflow tract (LVOT) dimensions are important for calculation of aortic valve areas and planning of valve repair. Mostly, LVOT areas are calculated from echocardiographic longitudinal measurements with the assumption of a round shape. Here, orthogonal phase contrast (PC) MRI with dynamic assessment of LVOT was compared to standard longitudinal cine MRI and 2D echocardiography.

Role of Global Longitudinal Strain in the Prediction of Outcome in Patients With Severe Aortic Valve Stenosis.

In the present study, we assessed the role of Global Longitudinal Strain (GLS) as a predictor of all-cause mortality in patients with severe aortic valve stenosis (AS), irrespective of their type of treatment. Data of 807 patients with AS receiving complete echocardiographic and clinical examination were retrospectively analyzed. Valve area <1 cm and sufficient image quality were inclusion criteria; patients with severe concomitant valvulopathy were excluded.

Biomarkers for Diagnosing and Staging of Fabry Disease.

Background: Fabry disease is an X-linked lysosomal storage disorder caused by deficient activity of α -galactosidase A which leads to progressive intracellular accumulation of globotriaosylceramide in tissues and organs including heart, kidney, vascular endothelium, the nervous system, the eyes and the skin. Cardiac involvement is common, leads to fatal complications and is mainly responsible for reduced life expectancy in Fabry disease. The exact staging of disease progression and timely initiation of treatment is essential in Fabry disease.

[A 59-year-old woman with upper abdominal pain and fever].

A 59-year-old woman suffered from fever and upper abdominal pain. The computed tomography (CT) scan revealed a liver lesion. Conventional imaging techniques (CT, magnetic resonance imaging, contrast-enhanced ultrasonography) did not allow for a consistent diagnosis.

Improvement of Fabry Disease-Related Gastrointestinal Symptoms in a Significant Proportion of Female Patients Treated with Agalsidase Beta: Data from the Fabry Registry.

Fabry disease, an X-linked inherited lysosomal storage disorder, is caused by mutations in the gene encoding α-galactosidase, GLA. In patients with Fabry disease, glycosphingolipids accumulate in various cell types, triggering a range of cellular and tissue responses that result in a wide spectrum of organ involvement. Although variable, gastrointestinal symptoms are among the most common and significant early clinical manifestations; they tend to persist into adulthood if left untreated.

Value of tissue Doppler-derived Tei index and two-dimensional speckle tracking imaging derived longitudinal strain on predicting outcome of patients with light-chain cardiac amyloidosis.

Prognosis of patients with light-chain cardiac amyloidosis (AL-CA) is poor. Speckle tracking imaging (STI) derived longitudinal deformation parameters and Doppler-derived left ventricular (LV) Tei index are valuable predictors of outcome in patients with AL-CA. We estimated the prognostic utility of Tei index and deformation parameters in 58 comprehensively phenotyped patients with AL-CA after a median follow-up of 365 days (quartiles 121, 365 days).

Echocardiographic Determinants of One-Year All-Cause Mortality in Patients With Chronic Heart Failure Complicated by Significant Functional Tricuspid Regurgitation.

Background: Right ventricular (RV) dysfunction plays an important role in chronic heart failure (CHF). We evaluated the echocardiographic determinants of 1-year all-cause mortality in CHF patients with clinically relevant functional tricuspid regurgitation (TR).

Methods And Results: A total of 101 consecutive CHF patients (mean age 74 ± 10 years, 53% male) with moderate or severe functional TR were enrolled.

Myocardial lipid content in Fabry disease: a combined H-MR spectroscopy and MR imaging study at 3 Tesla.

Background: Fabry disease is characterized by a progressive deposition of sphingolipids in different organ systems, whereby cardiac involvement leads to death. We hypothesize that lysosomal storage of sphingolipids in the heart as occurring in Fabry disease does not reflect in higher cardiac lipid concentrations detectable by H magnetic resonance spectroscopy (MRS) at 3 Tesla.

Methods: Myocardial lipid content was quantified in vivo by H-MRS in 30 patients (12 male, 18 female; 18 patients treated with enzyme replacement therapy) with genetically proven Fabry disease and in 30 healthy controls.

Multicenter Female Fabry Study (MFFS) - clinical survey on current treatment of females with Fabry disease.

Background: The aim of the present study was to assess manifestations of and applied treatment concepts for females with Fabry disease (FD) according to the current European Fabry Guidelines.

Methods: Between 10/2008 and 12/2014, data from the most recent visit of 261 adult female FD patients from six German Fabry centers were retrospectively analyzed. Clinical presentation and laboratory data, including plasma lyso-Gb3 levels were assessed.

Alpha-Galactosidase A p.A143T, a non-Fabry disease-causing variant.

Background: Fabry disease (FD) is an X-linked multisystemic disorder with a heterogeneous phenotype. Especially atypical or late-onset type 2 phenotypes present a therapeutical dilemma.

Methods: To determine the clinical impact of the alpha-Galactosidase A (GLA) p.