The volatility of Bitcoin and its role as a medium of exchange and a store of value.

Bitcoin is designed as a peer-to-peer cash system. To work as a currency, it must be stable or be backed by a government. In this paper, we show that the volatility of Bitcoin prices is extreme and almost 10 times higher than the volatility of major exchange rates (US dollar against the euro and the yen). The excess volatility even adversely affects its potential role in portfolios. Our analysis implies that Bitcoin cannot function as a medium of exchange and has only limited use as a risk-diversifier. In contrast, we use the deflationary design of Bitcoin as a theoretical basis and demonstrate that Bitcoin displays store of value characteristics over long horizons.

The Treatment of Primary Breast Cancer in Older Women With Adjuvant Therapy: A Retrospective Analysis of Data From Over 3000 Patients From the PATH Biobank, With Two-Year Follow-up.

BACKGROUND: Breast cancer is the most common cancer in women in Germany. Mortality from breast cancer has declined over the past 15 years, but less so in women aged 70 or older than in younger women. The discrepancy might be explained by age-related differences in treatment. METHODS: Data from the Patients' Tumor Bank of Hope (PATH) database of women who underwent adjuvant treatment for the treatment of an invasive primary tumor without distant metastases (year of diagnosis, 2006-2011) were retrospectively analyzed. The clinical and tumor-biological findings and treatment data over two years of follow-up were compared across three age groups (under age 50, ages 50 to 69, and ages 70 and up). Chi-square tests were carried out to reveal significant differences, and post-hoc multiple comparisons were performed with and without Bonferroni correction. Treatment data were adjusted for staging and grading and tested for age-dependence with logistic regression. RESULTS: Follow-up data were available for 3257 (65% ) of 4981 women, of whom 61% were in the middle age group and 22% in the oldest. Compared to women aged 50 to 69, those aged 70 and up less commonly received breast-conserving treatment (68.8% vs. 86.4% ), chemotherapy (27.5% vs. 44.1% ), radiotherapy (81.8% vs. 92.4% ), and trastuzumab (52.9% vs. 79.3% ; p<0.001 for all differences). All differences remained significant after stastistical adjustment. CONCLUSION: The cause of these age-related differences is unclear. It cannot be determined from these data whether concomitant disease, the older patients' individual decisions, or other factors were responsible for their not receiving treatment as often as the younger patients did.

Prognostic value of HPV-mRNA in sentinel lymph nodes of cervical cancer patients with pN0-status.

Up to 15% of patients with cervical cancer and pN0-status develop recurrent-disease. This may be due to occult metastatic spread of tumor cells. We evaluated the use of human-papillomavirus-(HPV)-mRNA as a molecular marker for disseminated tumor cells to predict the risk of recurrence. For this prospective, multi-center prognostic study, 189 patients free of lymphnode metastases by conventional histopathology could be analyzed. All patients underwent complete lymphadenectomy. Of each sentinel node (SLN) a biopsy was taken for the detection of HPV-E6-E7-mRNA. Median follow-up time after surgery was 8.1 years. HPV-mRNA could be detected in SLN of 52 patients (27.5%). Recurrence was observed in 22 patients. Recurrence-free-survival was significantly longer for patients with HPV-negative SLN (log rank p = 0.002). By Cox regression analysis the hazard ratio (95%CI) for disease-recurrence was 3.8 (1.5 - 9.3, p = 0.004) for HPV-mRNA-positive compared to HPV-mRNA-negative patients. After adjustment for tumor size as the most influential covariate the HR was still 2.8 (1.1 - 7.0, p = 0.030). In patients with cervical cancer and tumor-free lymph nodes by conventional histopathology HPV-mRNA-positive SLN were of prognostic value independent of tumor size. Particularly, patients with tumors larger than 20mm diameter could possibly benefit from further risk stratification using HPV-mRNA as a molecular marker.

Emergent surgical pulmonary embolectomy in a pregnant woman: case report and literature review.

Acute pulmonary embolism is a leading cause of death during pregnancy and delivery in the United States. We describe the case of a 25-year-old woman who presented in cardiogenic shock in week 38 of her first pregnancy. After the emergent cesarean delivery of a healthy male neonate, the mother underwent immediate surgical pulmonary embolectomy. We confirmed the diagnosis of pulmonary embolism intraoperatively by means of transesophageal echocardiography and removed large clots from the patient's pulmonary arteries. Mother and child were doing well, 27 months later. In addition to presenting our patient's case, we discuss the other relevant reports and the options for treating massive pulmonary embolism during pregnancy.

13th st. Gallen international breast cancer conference 2013: primary therapy of early breast cancer evidence, controversies, consensus - opinion of a german team of experts (zurich 2013).

The International Consensus Conference on the treatment of primary breast cancer takes place every two years in St. Gallen, Switzerland. The panel in St. Gallen is composed of international experts from different countries. From a German perspective, it seems reasonable to interpret the voting results in the light of AGO-recommendations and S3-guidelines for everyday practice in Germany. Consequently, a team of eight breast cancer experts, of whom two are members of the international St. Gallen panel, commented on the voting results of the St. Gallen Consensus Conference (2013). The main topics at this year's St. Gallen conference were surgical issues of the breast and axilla, radio-therapeutic and systemic treatment options, and the clinical relevance of tumour biology. The clinical utility of multigene assays for supporting individual treatment decisions was also intensively discussed.

Comparison of MammaPrint and TargetPrint results with clinical parameters in German patients with early stage breast cancer.

The 70-gene expression profile MammaPrint is a powerful prognostic indicator for disease outcome in breast cancer patients with improved prediction of recurrence risk compared to currently used guidelines. The microarray-based test TargetPrint further provides reliable, quantitative assessment of mRNA expression levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). This study was performed as a validation of MammaPrint and TargetPrint in an unselected German breast cancer population and was designed to determine the degree of concordance with currently applied clinical parameters. One hundred and forty cases of breast cancer stage I and II were classified as being low or high risk for distant metastasis using MammaPrint. Results were compared to current clinical risk classifications and adjuvant treatment management. Immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH)/chromogenic in situ hybridization (CISH) assessments of ER, PR and HER2 were further compared with gene expression read-outs using TargetPrint. Thirty-two percent of patients (19/59) with a poor prognosis-signature identified via MammaPrint did not receive adjuvant systemic treatment apart from endocrine therapy and were potentially undertreated; whereas 42% (35/77) of patients with a good prognosis-signature received chemotherapy and were potentially overtreated. Comparison of microarray receptor results with IHC and FISH/CISH were concordant in 97% for ER; 86% for PR; and 94% for HER2. In this German study population, MammaPrint would have resulted in altered treatment advice for adjuvant systemic therapy in 40% of patients. Furthermore, TargetPrint presented high concordance for ER, PR and Her2 with IHC and FISH/CISH analysis.

Multicentric and multifocal versus unifocal breast cancer: is the tumor-node-metastasis classification justified?

For classification of breast cancer (BC), tumor-node-metastasis (TNM) staging has been considered state of the art for more than 50 years. The T category is well defined, and in multicentric and multifocal tumors, tumor size is assessed by the largest tumor focus. The aim of this study was to compare multicentric/multifocal tumor spread in breast cancer with unifocal disease and to evaluate the diagnostic relevance of multifocality. A retrospective analysis was performed on survival related events in a series of 5,691 breast cancer patients between 1963 and 2007. By matched-pair analysis, patients were entered into two comparable groups of 288 patients after categorizing them as having multifocal/multicentric or unifocal breast cancers. Matching criteria were tumor size, grading, and hormone receptor status, which were equally distributed between both groups (P = 1.000 each). Disease free survival and the occurrence of relapse or of metastatic disease were evaluated. Cox's regression analysis was used for multivariate analysis. In the unifocal group, the mean breast cancer-specific survival time was 221.6 months as opposed to 203.3 months in the multicentric/multifocal group (P < 0.001, log-rank test). The occurrence of local relapse and distant metastasis was significantly increased in the multifocal group in comparison to the unifocal equivalent group (P < 0.001 and P < 0.003, respectively). Cox regression analysis for multivariate analyses demonstrated focality and centricity to be highly significant predictors for reduced overall survival (P = 0.016), local relapse (P = 0.001) and distant metastasis (P = 0.038). Tumor size, histopathological grading, hormone receptor status, and staging of lymph nodes are well-established prognostic parameters. Additionally, the number of foci should be considered as an independent prognostic parameter, which is currently not reflected in the TNM classification. We conclude that multicentric/multifocal BC is an independent BC risk factor and should be included in the risk assessment by re-evaluating the current TNM classification of the UICC.

Is the histomorphological concept of the female pelvic floor and its changes due to age and vaginal delivery correct?

AIMS: To compare the histomorphology of pelvic floor specimens of 94 female cadavers, ten male cadavers, and 24 female symptomatic patients who underwent pelvic floor surgery, and to evaluate the association of age, parity, and sex to myogenic and/or neurogenic changes to the levator ani muscle (LAM). METHODS: The pelvic floor was biopsied at the pubococcygeus, the iliococcygeus and the coccygeus muscle. After staining, signs for myogenic/neurogenic changes to the muscle were evaluated (fibrosis, variation in fiber diameter, centralization of nuclei, small angulated fibers, and type grouping). To identify the intact neuromuscular junction stainings with NCAM (neuronal cell adhesion molecule) and acetylcholinesterase (ACE) were used. RESULTS: A significant influence of age and parity on the histomorphological criteria of myogenic cell-damage was shown in this study. Although these criteria were found even in young nulliparous women, there was a significant increase in older or parous women with at least one vaginal delivery. We failed to demonstrate significant changes between the nulliparous LAM, the male LAM, and the LAM from women with prolapse and incontinence. None of the specimen showed any obvious evidence of neuropathy. CONCLUSIONS: We have evaluated histological criteria adapted from the examination of limb muscles in the LAM of nulliparous young women. "Myogenic changes" seem to be a normal finding in the LAM. The increase of these changes with aging and parity points to mechanical stress to the LAM as the most plausible causative factor. We propose that further studies using histomorphological techniques of the pelvic floor muscle in nulliparous and parous women should clarify the potential role of our histological findings.

Patients with recurrent breast cancer: does the primary axillary lymph node status predict more aggressive tumor progression?

BACKGROUND: The extent of axillary lymph node involvement represents the foremost important prognostic parameter in primary breast cancer, and, thus, is one of the main determinants for subsequent systemic treatment. Nevertheless, the relevance of the initial axillary lymph node status on survival after disease recurrence is discussed controversially. Persisting prognostic impact after relapse would identify lymph node status as a marker for tumor biology, in contrast to a simply time-dependent phenomenon. METHOD: Retrospective analysis of 813 patients with locoregional or distant recurrence of primary breast cancer, who were primarily diagnosed with their disease at the I. Frauenklinik, Ludwig-Maximilians-University, Munich, and the University Hospital in Berlin-Charlottenburg, Germany, between 1963 and 2000. To be eligible, patients were required to have been treated for resectable breast cancer free of distant disease at the time of primary diagnosis, and must have undergone systematic axillary lymph node dissection. Patients with unknown tumor size or nodal status were excluded from the study. All data were gathered contemporaneously and compared with original patients files, as well as the local cancer registry, ensuring high quality of data. The median observation time was 60 (standard deviation 44) months. RESULTS: At time of primary diagnosis, 273 patients (33.6%) were node-negative, while axillary lymph node metastases were detected in 540 patients (66.4%). In univariate analysis tumor size, axillary lymph node status, histopathological grading, hormone receptor status, as well as peritumoral lymphangiosis and haemangiosis carcinomatosa were significantly correlated with survival after relapse (all, P < 0.0001). Kaplan-Meier analysis estimated the median survival time after relapse in node-negative patients to be 42 months (31-52 months, 95% CI), and 20 months in patients with 1-3 axillary lymph node metastases (16-24 months, 95% CI), compared to 13 months in patients with at least 4 involved axillary nodes (12-15 months, 95% CI). Multivariate logistic regression analysis, allowing for tumor size, axillary lymph node status, histopathological grading, presence of lymphangiosis carcinomatosa, relapse site and disease-free interval confirmed all parameters, except of histopathological grading (P = 0.14), as significant, independent risk factors for cancer associated death. Subgroup analyses, accounting for site of relapse and duration of disease-free interval, confirmed primary lymph node status as independent predictor for cancer-associated death after relapse. CONCLUSION: Lymph node involvement at primary diagnosis of breast cancer patients predicts an unfavorable outcome after first recurrence, independently of the site of relapse and disease-free interval. These observations support the hypothesis that primary lymph node involvement is not a merely time-dependent indicator for tumor progression, but indicates tumors with aggressive biological behavior.

Urinary and anal incontinence after vacuum delivery.

OBJECTIVES: To evaluate urinary and fecal incontinence symptoms, and occult anal sphincter defects in women after vacuum and spontaneous vaginal delivery. STUDY DESIGN: In a case-control study, 50 primiparous women delivered by vacuum extraction were compared to 50 women delivered spontaneously. Urinary and anal incontinence symptoms, pelvic floor muscle strength and sphincter defects on endoanal ultrasound were evaluated 6-24 weeks postpartum. RESULTS: New anal incontinence symptoms after childbirth were found in 30% of the vacuum group compared to 34% of the controls, new urinary incontinence symptoms in 28 and 42%, respectively (not significant). After excluding Grade III perineal tear, sonographic sphincter defects were found in 11 (27.5%) after vacuum delivery compared to 4 (10%) after spontaneous delivery (P<0.05, chi(2)-test). CONCLUSION: Anal and urinary incontinence symptoms are frequent after vaginal delivery. Vacuum delivery causes more sonographic sphincter defects but appears to cause no more harm to pelvic floor function than spontaneous vaginal delivery.

Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases.

BACKGROUND: The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment. METHOD: Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R(0) resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15 degrees of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years. RESULTS: The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients ( n=810) and in the lateral hemisphere of the breast in 66.4% ( n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location ( P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor ( P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98). CONCLUSION: We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.

Long-term efficacy of pelvic floor re-education with EMG-controlled biofeedback.

OBJECTIVE: To evaluate the long-term efficacy of pelvic floor re-education (PFR) with EMG-controlled biofeedback in the treatment of female genuine stress or mixed incontinence. STUDY DESIGN: Between 1995 and 1998, 36 women completed a pelvic floor muscle training with a biofeedback device for 3-6 months. A mean of 26 months later, a follow-up examination was performed. RESULTS: The prevalence of lower urinary tract symptoms decreased significantly immediately after the training but increased again at the long-term follow-up. Levator ani muscle strength improved after the treatment and remained significantly better for long-term follow-up. Immediately after the program, 25 (70%) women reported cure or improvement of stress incontinence. At the long-term follow-up, 17 (47%) reported the same result. CONCLUSIONS: About half of the patients after PFR with biofeedback are still improved or cured after 26 months. Women should be counseled about the long-term efficacy and about the necessity of maintaining training.

The prognostic impact of a prolonged second stage of labor on maternal and fetal outcome.

OBJECTIVE: While obstetrical management has changed significantly over years, the optimal duration of the second stage of labor still remains to be defined. The purpose of this study was to evaluate the effect of the duration of labor on fetal distress and maternal perinatal morbidity. METHODS: There were 1457 consecutive patients delivered of a singleton fetus in cephalic presentation beyond the 34th week of gestation at the I. Frauenklinik, Ludwig-Maximilians University, Munich between May 1999 and June 2000. The 257 patients (17.6%), who underwent cesarean section prior to or during labor, were excluded from the study. Of the 1200 vaginal deliveries, 1017 (84.8%) were normal spontaneous deliveries, while 183 (15.2%) were instrumentally assisted. Data were contemporaneously collected and analyzed for the presence of severe pelvic floor damage, maternal hemorrhage, maternal fever, delayed involution of the uterus, fetal acidosis and APGAR score, and the necessity for admitting the newborn to the intensive care unit (NICU). A second stage duration of > 2 hr was considered to be prolonged. RESULTS: The mean duration of the second stage of labor was 70 min (range 2-387, SD 73 min). For 952 patients (79.3%), the second stage was less than 2 h. For 47 patients (3.9%), it exceeded 4 h. A prolonged duration of the second stage was not associated with low Apgar scores 5 and 10 min postpartum (P = 0.76 and P = 0.38, respectively), a higher incidence of umbilical artery pH levels of < 7.20 (P = 0.60), nor with an increased rate of admission to the NICU (P = 0.24). A significant increase in the rate of maternal blood loss was noted after long second stages (1.84 g/dl median difference between the intrapartum and postpartum hemoglobin level) in comparison to patients with normal duration of second stage (0.79 g/dl), both by univariate (P < 0.0001) and multivariate (P < 0.001) analysis. The incidence of third degree anal sphincter tears was significantly correlated with a prolonged duration of second stage in univariate analysis (7.7%, P = 0.001), but not in multivariate analysis after allowing for duration of the second stage, maternal age, birth weight, episiotomy, and mode of delivery (P = 0.26). CONCLUSION: There is no evidence that prolonged second stage of labor is a serious disadvantage to the fetus, if adequate monitoring is provided. Because the increase of maternal morbidity in patients with prolonged labor may be partially attributed to a higher rate of operative procedures in these patients, interventions should not be solely based on the elapsed time after full cervical dilatation.