Transcatheter aortic valve implantation or surgical aortic valve replacement as redo procedure after prior coronary artery bypass grafting

The perioperative risk for redo surgical aortic valve replacement (S-AVR) in patients with severe aortic stenosis and prior coronary artery bypass grafting (CABG) is increased. Transcatheter aortic valve implantation (TAVI) represents an alternative. We assessed the perioperative and mid-term clinical outcome of patients undergoing S-AVR or TAVI.

[Surgical treatment options in end-stage heart failure]

Despite significant improvements in pharmacological therapy heart failure is still one of the leading causes for death in the Western World. The gold standard treatment of end-stage heart failure remains cardiac transplantation, but there is a great excess of eligible candidates compared with the low number of suitable donor organs. The variety of surgical organ preserving treatment strategies has significantly increased during the last 20 years, intenting either to delay or even to prevent the need for cardiac transplantation. An individually tailored surgical concept should be considered as an alternative in any heart failure patient who has reached the limits of pharmacologic therapy. This article gives an overview about current and potential future therapeutic options in end-stage heart failure.

[Surgical options in the treatment of chronic venous ulcers]

Surgery offers several options in prevention of chronic venous insufficiency and its sequelae. Both the operation on veins with valve dysfunction to reduce reflux and the elimination of obstruction in thrombosed veins aim for the reduction of venous hypertension. Elevated venous pressure, impairment of cutaneous capillaries and a chronic inflammatory process result in sclerosis of skin and subcutaneous tissue and might proceed to the fascia resulting in a chronic compartment syndrome. Non- healing chronic venous ulcers under conservative therapy for more than three months may be treated by vein-surgery, local wound care therapy like shaving and negative pressure treatment and if necessary by lowering of elevated intracompartimental pressure by fasciotomy or even fasciectomy.

[Osteoporosis - whom to treat? The importance of FRAX® in Switzerland]

The WHO fracture risk assessment tool FRAX® is a computer based algorithm that provides models for the assessment of fracture probability in men and women. The approach uses easily obtained clinical risk factors (CRFs) to estimate 10-year probability of a major osteoporotic fracture (hip, clinical spine, humerus or wrist fracture) and the 10-year probability of a hip fracture. The estimate can be used alone or with femoral neck bone mineral density (BMD) to enhance fracture risk prediction. FRAX® is the only risk engine which takes into account the hazard of death as well as that of fracture. Probability of fracture is calculated in men and women from age, body mass index, and dichotomized variables that comprise a prior fragility fracture, parental history of hip fracture, current tobacco smoking, ever long-term use of oral glucocorticoids, rheumatoid arthritis, other causes of secondary osteoporosis, daily alcohol consumption of 3 or more units daily. The relationship between risk factors and fracture probability was constructed using information of nine population-based cohorts from around the world. CRFs for fracture had been identified that provided independent information on fracture risk based on a series of meta-analyses. The FRAX® algorithm was validated in 11 independent cohorts with in excess of 1 million patient-years, including the Swiss SEMOF cohort. Since fracture risk varies markedly in different regions of the world, FRAX® models need to be calibrated to those countries where the epidemiology of fracture and death is known. Models are currently available for 31 countries across the world. The Swiss-specific FRAX® model was developed very soon after the first release of FRAX® in 2008 and was published in 2009, using Swiss epidemiological data, integrating fracture risk and death hazard of our country. Two FRAX®-based approaches may be used to explore intervention thresholds. They have recently been investigated in the Swiss setting. In the first approach the guideline that individuals with a fracture probability equal to or exceeding that of women with a prior fragility fracture should be considered for treatment is translated into thresholds using 10-year fracture probabilities. In that case the threshold is age-dependent and increases from 16 % at the age of 60 ys to 40 % at the age of 80 ys. The second approach is a cost-effectiveness approach. Using a FRAX®-based intervention threshold of 15 % for both, women and men 50 years and older, should permit cost-effective access to therapy to patients at high fracture probability in our country and thereby contribute to further reduce the growing burden of osteoporotic fractures.

[Epidemiology and burden of osteoporosis in Switzerland]

With increasing life expectancy and a growing proportion of elderly in the Swiss population, the burden of osteoporosis increases continuously. Every other woman and every fifth man aged 50 years or older will suffer an osteoportic fracture during her or his remaining lifetime. While the absolute number of hospitalizations for hip fractures has stabilized between year 2000 and 2007, the total number of hospitalizations for osteoporotic fractures has increased to 16'200 (+ 16 %) and 5'600 (+ 20 %) in women and men, respectively. Thus, osteoporosis continues belonging to those chronic diseases imposing the highest economic burden to the Swiss healthcare system, trend increasing. In addition, the risk of subsequent fractures as well as the adjusted mortality risk increases significantly after a first osteoporotic fracture. Should appropriate measures not be implemented in the near future, so will osteoporosis become one of the key challenges for the Swiss healthcare system within the coming years.

Homeodomain-only protein HOP is a novel modulator of late differentiation in keratinocytes

The homeodomain-only protein (HOP) contains an atypical homeodomain which is unable to bind to DNA due to mutations in residues important for DNA binding. Recently, HOP was reported to regulate proliferation/differentiation homeostasis in different cell types. In the present study, we performed transcriptional profiling of cultured primary human keratinocytes and noted a robust induction of HOP upon calcium-induced cell differentiation. Immunohistochemistry of human skin localized HOP to the granular layer in the epidermis. Overexpression of HOP using a lentiviral vector up-regulated FLG and LOR expression during keratinocyte differentiation. Conversely, decreasing HOP expression using small interfering RNA markedly reduced the calcium-induced expression of late markers of differentiation in vitro, with the most prominent effect on profilaggrin (FLG) mRNA. Moreover, mRNA levels of profilaggrin and loricrin were downregulated in the epidermis of HOP knockout mice. Analysis of skin disorders revealed altered HOP expression in lichen planus, psoriasis and squamous cell carcinoma (SCC). Our data indicate that HOP is a novel modulator of late terminal differentiation in keratinocytes.

Induction of p38, tumour necrosis factor-α and RANTES by mechanical stretching of keratinocytes expressing mutant keratin 10R156H

Epidermolytic hyperkeratosis (bullous congenital ichthyosiform erythroderma), characterized by ichthyotic, rippled hyperkeratosis, erythroderma and skin blistering, is a rare autosomal dominant disease caused by mutations in keratin 1 or keratin 10 (K10) genes. A severe phenotype is caused by a missense mutation in a highly conserved arginine residue at position 156 (R156) in K10.

Expression patterns of Bmi-1 and p16 significantly correlate with overall, disease-specific, and recurrence-free survival in oropharyngeal squamous cell carcinoma

BACKGROUND: The objective of this study was to link expression patterns of B-cell-specific Moloney murine leukemia virus integration site 1 (Bmi-1) and p16 to patient outcome (recurrence and survival) in a cohort of 252 patients with oral and oropharyngeal squamous cell cancer (OSCC). METHODS: Expression levels of Bmi-1 and p16 in samples from 252 patients with OSCC were evaluated immunohistochemically using the tissue microarray method. Staining intensity was determined by calculating an intensity reactivity score (IRS). Staining intensity and the localization of expression within tumor cells (nuclear or cytoplasmic) were correlated with overall, disease-specific, and recurrence-free survival. RESULTS: The majority of cancers were localized in the oropharynx (61.1%). In univariate analysis, patients who had OSCC and strong Bmi-1 expression (IRS >10) had worse outcomes compared with patients who had low and moderate Bmi-1 expression (P = .008; hazard ratio [HR], 1.82; 95% confidence interval [CI], 1.167-2.838); this correlation was also observed for atypical cytoplasmic Bmi-1 expression (P = .001; HR, 2.164; 95% CI, 1.389-3.371) and for negative p16 expression (P < .001; HR, 0.292; 95% CI, 0.178-0.477). The combination of both markers, as anticipated, had an even stronger correlation with overall survival (P < .001; HR, 8.485; 95% CI, 4.237-16.994). Multivariate analysis demonstrated significant results for patients with oropharyngeal cancers, but not for patients with oral cavity tumors: Tumor classification (P = .011; HR, 1.838; 95%CI, 1.146-2.947) and the combined marker expression patterns (P < .001; HR, 6.254; 95% CI, 2.869-13.635) were correlated with overall survival, disease-specific survival (tumor classification: P = .002; HR, 2.807; 95% CI, 1.477-5.334; combined markers: P = .002; HR, 5.386; 95% CI, 1.850-15.679), and the combined markers also were correlated with recurrence-free survival (P = .001; HR, 8.943; 95% CI, 2.562-31.220). CONCLUSIONS: Cytoplasmic Bmi-1 expression, an absence of p16 expression, and especially the combination of those 2 predictive markers were correlated negatively with disease-specific and recurrence-free survival in patients with oropharyngeal cancer. Therefore, the current results indicate that these may be applicable as predictive markers in combination with other factors to select patients for more aggressive treatment and follow-up. Cancer 2011;. © 2011 American Cancer Society.

[Local treatment of chronic skin wounds in a Swiss out-patient wound centre 2010]

In Switzerland around 30,000 patients suffer from chronic skin wounds. Appropriate topical wound care along with treatment of the causes of the wounds enables to heal a lot of these patients and to avoid secondary disease such as infections. Thereby, the final goal of wound care is stable reepithelisation. Based on experience with chronic leg ulcers mainly in our out-patient wound centre, we give a survey of the wound dressings we actually use and discuss their wound-phase adapted application. Furthermore, we address the two tissue engineering products reimbursed in Switzerland, Apligraf and EpiDex, as well as the biological matrix product Oasis. The crucial question, which treatment options will be offered in future to the wound patients by our health regulatory and insurance systems, is open to debate.

Recombinant human factor VIIa prevents hysterectomy in severe postpartum hemorrhage: single center study

Abstract Objective: To evaluate the effectiveness of human recombinant activated factor VII (rhFVIIa, NovoSeven) in avoiding hysterectomy postpartum in the management of severe postpartum hemorrhage (PPH). Methods: We performed a prospective cohort study at our university tertiary care center. Patients with severe post partum hemorrhage (blood loss >2000 mL) and failed medical and uterus-preserving surgical management, were treated with intravenous bolus administration of rhVIIa. Main outcome measures were cessation of bleeding, postpartum hysterectomy and thromboembolic events. Results: In 20/22 patients included, PPH was caused primarily by uterine atony, including 7 (32%) with additional lower genital tract lesion; in two women, it was due to pathologic placentation (placenta increta, 9%). One case of amniotic fluid embolism and one woman with uterine inversion were included. Recombinant hFVIIa was successful in stopping the PPH and in preventing a hysterectomy in 20/22 women (91%). The remaining two patients with persistent bleeding despite rhFVIIa treatment, who underwent postpartum hysterectomy, had placenta increta. No thromboembolic event was noticed. Conclusions: This study describes the largest single center series of rhFVIIa treatment for fertility preservation in severe postpartum hemorrhage published to date. Our data suggest that administration of rhFVIIa is effective in avoiding postpartum hysterectomy after conservative medical and surgical measures have failed. Although randomized studies are lacking, rhFVIIa should be considered as a second-line therapeutic option of life-threatening postpartal bleeding, in particular if preservation of fertility is warranted and hysterectomy is to be avoided.

[Sarcomas and mixed mesodermal tumors of the uterus]

Malignant mesodermal tumors of the uterus are an inhomogenous group of uterine malignancies with different pathogenesis, clinical presentation and prognosis. These rare tumors represent approximately 1 % of all uterine malignancies. The aggressive carcinosarcomas or mixed muellerian tumors are defined by mixed malignant epithelial and malignant mesodermal histopathology and are of the same precursor cell origin like endometrial cancer. Thus, carcinosarcomas were reclassified by the FIGO as an aggressive type of endometrial cancer and treated like type II endometrial cancer. Adenosarcomas are also mixed tumors with benign epithelial proliferation and malignant mesodermal cell growth, have a good prognosis and represent less than 5 % of all mesodermal uterine malignancies. Besides carcinosarcomas, the pure mesodermal leiomyosarcomas are the most common mesodermal malignancies. Patients with leiomyosarcamos are usually perimenopausal, and although more than half of the patients present with symptoms, diagnosis occurs incidentally in most cases in final histopathologic workup of an excised putative myoma or uterus. Adequate anamnesis, gynecologic examination and careful imaging by transvaginal ultrasound in the preoperative setting might hint to correct differential diagnosis in many cases. Overall the prognosis of uterine leiomyomas is poor. Malignancies of the endometrial stroma are very rare and divided in two subgroups, the mostly estrogen receptor positive endometrial stromal sarcoma, which occur preferably in premenopausal women and show a favorable prognosis, and the very aggressive undifferentiated endometrial sarcomas. The more rare undifferentiated endometrial sarcomas occur in postmenopausal women and most patients die in the first two years after diagnosis. Risk stratification of preoperative differential diagnosis requires improvements and the correct histopathologic workup of mesodermal uterine malignancies is still a challenge for pathologists.

Advanced heart failure - treatment options beyond medical management

Improvement of heart failure therapy has led to a far better survival and quality of life of patients. Treatment of the underlying disease, patient education and improvement of compliance and consequent upgrading of medical heart failure therapy often delays further progression to an advanced stage of heart failure. Nevertheless heart failure remains a chronic progressive disease and it is up to the treating clinician to identify the signs of advanced heart failure in a timely manner in order to evaluate patients for further treatment strategies such as heart transplantation. This article should help define advanced heart failure and illustrate how patients are evaluated for further therapy. Outcome of heart transplantation or mechanically assisted circulatory support is strongly associated to proper patient selection and timing.

ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS)

Cardiovascular disease (CVD) due to atherosclerosis of the arterial vessel wall and to thrombosis is the foremost cause of premature mortality and of disability-adjusted life years (DALYs) in Europe, and is also increasingly common in developing countries.1 In the European Union, the economic cost of CVD represents annually E192 billion1 in direct and indirect healthcare costs. The main clinical entities are coronary artery disease (CAD), ischaemic stroke, and peripheral arterial disease (PAD). The causes of these CVDs are multifactorial. Some of these factors relate to lifestyles, such as tobacco smoking, lack of physical activity, and dietary habits, and are thus modifiable. Other risk factors are also modifiable, such as elevated blood pressure, type 2 diabetes, and dyslipidaemias, or non-modifiable, such as age and male gender. These guidelines deal with the management of dyslipidaemias as an essential and integral part of CVD prevention. Prevention and treatment of dyslipidaemias should always be considered within the broader framework of CVD prevention, which is addressed in guidelines of the Joint European Societies’ Task forces on CVD prevention in clinical practice.2 – 5 The latest version of these guidelines was published in 20075; an update will become available in 2012. These Joint ESC/European Atherosclerosis Society (EAS) guidelines on the management of dyslipidaemias are complementary to the guidelines on CVD prevention in clinical practice and address not only physicians [e.g. general practitioners (GPs) and cardiologists] interested in CVD prevention, but also specialists from lipid clinics or metabolic units who are dealing with dyslipidaemias that are more difficult to classify and treat.