Is the current concept of recurrent ovarian carcinoma as a chronic disease also applicable in platinum resistant patients?

Purpose: The treatment of recurrent ovarian carcinoma (ROC) has become increasingly oriented according to the therapy principles of a chronic disease. We evaluated whether it is justifiable to also apply this concept to the treatment of platinum resistant patients with their known poor prognosis and short overall survival (OS). Methods: We analyzed the overall courses of 85 unselected ROC patients and defined the following groups: A, platinum resistant patients (n=39); subgroup A.1, those who received no or at maximum one line of palliative chemotherapy (n=15, 38.5%); subgroup A.2, those who received≥two therapy lines (n=24, 61.5%); B, platinum sensitive patients, n=46. Results: Group A had significantly lower OS than group B (median: 16 vs. 25months; p=0.019). Group A.1 had significantly worse outcome compared to group A.2 (median: 5 vs. 21.5months; p<0.001). The comparison between study group A.2 and group B showed comparable survival rates (p=0.738). Considering only the patients who had completed treatment courses, the median number of therapy lines administered was higher in group A.2 than in group B (4 vs. 3; p=0.008). Conclusions: There is not only the known dichotomy between platinum sensitive and resistant ROC patients, but rather also within the platinum resistant subgroup itself. There is a considerably large subgroup of platinum resistant patients who will subsequently enter a phase where multiple treatment programs will be considered and administered. These patients have similar survival rates compared to those from the platinum sensitive patient group and the therapy principles of a chronic disease are applicabl

A First Principles Derivation of Energy Conserving Momentum Jumps in Surface Hopping Simulations

The fewest switches surface hopping (FSSH) method proposed by Tully in 1990 [J. C Tully, J. Chem. Phys. 93, 1061 (1990)] -- along with its many later variations -- is basis for most practical simulations of molecular dynamics with electronic transitions in realistic systems. Despite its popularity, a rigorous formal derivation of the algorithm has yet to be achieved. In this paper, we derive the energy conserving momentum jumps characterizing FSSH from the perspective of quantum trajectory surface hopping (QTSH [C. C. Martens, J. Phys. Chem. A 123, 1110 (2019)]. In the limit of localized nonadiabatic transitions, simple mathematical and physical arguments allow the FSSH algorithm to be derived from first principles. For general processes, the quantum forces characterizing the QTSH method provides accurate results for nonadiabatic dynamics with rigorous energy conservation at the ensemble level within the consistency of the underlying stochastic surface hopping without resorting to the artificial momentum rescaling of FSSH.Comment: 11 pages, 4 figure

Strictly defined familial male breast cancer

The term "familial male breast cancer” is often misleading, because in the breast cancer families reported in the literature, the vast majority of the patients were women and only a few were men. In this report, we present the rare case of a strictly defined familial male breast cancer (MBC) in which exclusively men were diagnosed with breast cancer. Three of four brothers developed the disease between the age of 46 and 64years within a period of 21years whereas all female relatives remained unaffected. The three affected men did not show the typical known clinical and genetic risk factors for MBC. An X-linked recessive inheritance may be possible in these cases. One way to potentially improve the identification of the causes of MBC could be a through a strictly studying families in which the male members were exclusively diagnosed with this malignancy. This approach emphasizes familial MBC as a distinct entity and not only as a variant of female breast cance

Cannabinoid hyperemesis syndrome: an underreported entity causing nausea and vomiting of pregnancy

Introduction: In the western world, cannabis is the most widely used drug of abuse. Cannabinoid hyperemesis syndrome, which seems to be a rare paradoxical reaction in individuals with a particular predisposition, is characterized by cyclic severe nausea and vomiting in long-term cannabis users. While the symptoms are unresponsive to antiemetic drugs, compulsive hot baths result in a considerable symptom relief. Methods: We report the first case of cannabinoid hyperemesis syndrome in pregnancy. A 26-year-old patient was admitted to our clinic in the 10th week of gestation. Conclusion: Before undertaking time-consuming and expensive medical examinations to rule out other medical reasons for therapy-resistant hyperemesis in pregnancy, obstetricians should determine whether compulsive bathing or showering provides symptomatic relief and ask specific questions regarding possible/suspected cannabis consumptio

Personalized Estimate of Chemotherapy-Induced Nausea and Vomiting: Development and External Validation of a Nomogram in Cancer Patients Receiving Highly/Moderately Emetogenic Chemotherapy.

Chemotherapy-induced nausea and vomiting (CINV) is presented in over 30% of cancer patients receiving highly/moderately emetogenic chemotherapy (HEC/MEC). The currently recommended antiemetic therapy is merely based on the emetogenic level of chemotherapy, regardless of patient's individual risk factors. It is, therefore, critical to develop an approach for personalized management of CINV in the era of precision medicine.A number of variables were involved in the development of CINV. In the present study, we pooled the data from 2 multi-institutional investigations of CINV due to HEC/MEC treatment in Asian countries. Demographic and clinical variables of 881 patients were prospectively collected as defined previously, and 862 of them had full documentation of variables of interest. The data of 548 patients from Chinese institutions were used to identify variables associated with CINV using multivariate logistic regression model, and then construct a personalized prediction model of nomogram; while the remaining 314 patients out of China (Singapore, South Korea, and Taiwan) entered the external validation set. C-index was used to measure the discrimination ability of the model.The predictors in the final model included sex, age, alcohol consumption, history of vomiting pregnancy, history of motion sickness, body surface area, emetogenicity of chemotherapy, and antiemetic regimens. The C-index was 0.67 (95% CI, 0.62-0.72) for the training set and 0.65 (95% CI, 0.58-0.72) for the validation set. The C-index was higher than that of any single predictor, including the emetogenic level of chemotherapy according to current antiemetic guidelines. Calibration curves showed good agreement between prediction and actual occurrence of CINV.This easy-to-use prediction model was based on chemotherapeutic regimens as well as patient's individual risk factors. The prediction accuracy of CINV occurrence in this nomogram was well validated by an independent data set. It could facilitate the assessment of individual risk, and thus improve the personalized management of CINV

Platform Leadership: Managing Boundaries for the Network Growth of Digital Platforms

This study aims to generate a systematic understanding of how digital platform firms can attain platform leadership. We explore the question by casting a boundary management lens over the complex network of interactions on a digital platform. Firms are faced with various boundaries—boundaries of efficiency, competence, power, identity, and ties—and must carefully address tensions within diverse groups of actors with their own interests. We conducted an in-depth case study on China’s largest online ticketing firm and established two contributions for attaining platform leadership. First, we conceptualized the development of a digital platform as a set of technology-based boundary management mechanisms (functional multiplexing, scope expansion, community curation, actor empowerment, and positional escalation) that includes a combination of boundary spanning, erecting, and reinforcing. Second, we uncovered the network dynamics of a digital platform by explicating the synergies and tensions of boundary management. Considering our novel findings, this study offers managerial and design guidelines for a digital platform by advocating an integrative view of boundary management. We present a multidimensional framework that includes five boundaries and four types of networks (dyadic, interconnected, intraconnected, and external) for future analysis of networks built on digital platforms

An indicator of cancer: downregulation of Monoamine Oxidase-A in multiple organs and species

<p>Abstract</p> <p>Background</p> <p>Identifying consistent changes in cellular function that occur in multiple types of cancer could revolutionize the way cancer is treated. Previous work has produced promising results such as the identification of p53. Recently drugs that affect serotonin reuptake were shown to reduce the risk of colon cancer in man. Here, we analyze an ensemble of cancer datasets focusing on genes involved in the serotonergic pathway. Genechip datasets consisting of cancerous tissue from human, mouse, rat, or zebrafish were extracted from the GEO database. We first compared gene expression between cancerous tissues and normal tissues for each type of cancer and then identified changes that were common to a variety of cancer types.</p> <p>Results</p> <p>Our analysis found that significant downregulation of MAO-A, the enzyme that metabolizes serotonin, occurred in multiple tissues from humans, rodents, and fish. MAO-A expression was decreased in 95.4% of human cancer patients and 94.2% of animal cancer cases compared to the non-cancerous controls.</p> <p>Conclusion</p> <p>These are the first findings that identify a single reliable change in so many different cancers. Future studies should investigate links between MAO-A suppression and the development of cancer to determine the extent that MAO-A suppression contributes to increased cancer risk.</p

Systemic therapy developments and their effects regarding the current concept of recurrent ovarian carcinoma as a chronic disease

Purpose: To demonstrate how the current concept of recurrent ovarian carcinoma (ROC) as a chronic disease resulted in developments in the systemic treatment strategies and outcome over time. Methods: We compared therapy type and course of a population-based cohort whose recurrent disease was diagnosed from 1990 to 2006. We divided the patients into two subgroups depending on the year of diagnosis of ROC (group A 1990-1997, n=70; group B 1998-2006, n=63). Results: Both study groups showed similar results in survival (median recurrent disease-specific survival—A 18 months vs. B 19 months; P=0.549). In group B, the patients had significantly fewer combination therapies administered [12.0% vs. 24.1%; odds ratio (OR) 0.43; 95% confidence interval (CI) 0.23-0.81; P=0.0057], received more therapy lines (≥3 lines 56.1% vs. 31.1%; OR 3.10; 95% CI 1.37-7.17; P=0.005) and had significantly longer times of treatment (TT) in relation to the survival time (ST; mean TT/ST-ratio 57.5% vs. 47.5%; difference of the mean values B-A=−10.02; 95%CI −17.99 to −2.05; P=0.014). Conclusions: The finding that survival of ROC patients could not be improved over time should not necessarily be viewed with undue pessimism regarding the general therapy situation. In the more recent study period, a similar outcome could be achieved with less aggressive treatment regimens, i.e., with fewer combination therapies and with longer treatment periods using less toxic agents. When a disease which requires periodic chemotherapy to control progressive course is increasingly treated with a strategy that permits stabilization with limited cumulative toxicity, then the requirements of a chronic disease management have been fulfille

Antenatal corticosteroids for fetal lung maturation in threatened preterm delivery: indications and administration

Introduction: Antenatal maternal administration of corticosteroids has been shown to reduce morbidity and mortality rates in preterm delivery. Threatened spontaneous or medically indicated preterm delivery for maternal or fetal indications between 24 and 34weeks of gestation with unknown fetal lung maturity status are indications for antenatal corticosteroid administration. Recent studies have challenged current practice of antenatal glucocorticoid use. The goal of this expert letter is to provide recommendations based for the clinical use of antenatal glucocorticoids based on the current evidence from published studies. Methods: The published literature (PubMed search), as well as the recommendations of other national societies, has been searched and taken into consideration for these recommendations. Results/conclusions: The standard regimen of antenatal corticosteroids involves a single course of 2×12mg betamethasone administered intramuscularly within 24h. The administration of corticosteroids usually is performed between 24 and 34weeks gestation. However, under particular circumstances it may be beneficial even at 23weeks and at 35-36weeks of gestation. The evidence to date is clearly against the routine administration of multiple antenatal steroid courses. In special clinical situations, a second course of betamethasone ("rescue course”) may be justifiable. Tocolysis during administration of steroids is not routinely indicated in the absence of contractions, cervical shortening or rupture of membrane

Maternal request: a reason for rising rates of cesarean section?

Objective: The rising rate of cesarean sections (CS), especially those on maternal request, is an important obstetric care issue. The aim of this two-point cross-sectional study was to evaluate the prevalence of CS and their indications. Methods: We performed a retrospective chart review of the indications of all CS performed at a tertiary care clinic in Switzerland in 2002 and 2008. Chi-square, Student's t and Mann-Whitney U tests were performed to identify significant differences. Results: The number of CS rose from 23.3% (371 out of 1,594 total life births) in 2002 to 27.5% (513 out of 1,866) in 2008 (p=0.005). Of all deliveries, the rate of CS on maternal request and, among these, especially those requested after previous CS, increased significantly (2.1 vs. 5.1% and 0.3 vs. 1.2%, respectively). The number of CS due to previous traumatic birth experience nearly doubled (0.7 vs. 1.2%, not significant). Maternal and fetal complications were rare but not negligible in the subset of low-risk patients requesting CS. Conclusions: The study demonstrated a significant increase in CS on maternal request, especially in case of previous CS. The findings of this study support the need for specific counseling strategies for women requesting delivery by C