VE/VCO2 slope predicts RV dysfunction and mortality after left ventricular assist device: a fresh look at cardiopulmonary stress testing for prognostication

Journal of Artificial Organs - Preoperative cardiopulmonary exercise testing (CPET) is well validated for prognostication before advanced surgical heart failure therapies, but its role in...     

Guided tooth preparation device fabricated with a complete digital workflow: A dental technique

Guided tooth preparations allow clinicians to provide fixed dental prostheses for dentate patients in an efficient manner. One approach uses a digital preparation device technique where the preparation of a tooth needing a crown is guided by a device. Compared with conventional techniques, this method allows for accurate abutment preparation more efficiently and with improved quality. By controlling tooth preparation, this method preserves natural tooth structure and provides adequate clearance for the restorative material. To illustrate this technique, an adhesive minimally invasive fixed complete-mouth rehabilitation was provided by using a 3D-printed digital preparation device.     

Extramedullary disease portends poor prognosis in multiple myeloma and is over-represented in high-risk disease even in the era of novel agents

Background

Extramedullary disease is an uncommon manifestation in multiple myeloma and can either accompany newly diagnosed disease or develop with disease progression or relapse. We evaluated the impact of this disease feature on patients'' outcome in the context of novel agents.

Design and Methods

We analyzed clinical and biological features of extramedullary disease in 936 patients with multiple myeloma enrolled in Total Therapy protocols, 240 patients in non-Total Therapy protocols, and 789 non-protocol patients, all of whom had baseline positron emission tomography scans to document extramedullary disease at diagnosis and its subsequent development at the time of disease progression or relapse.

Results

The most common sites for extramedullary disease at diagnosis were skin and soft tissue whereas liver involvement was the striking feature in extramedullary disease at disease relapse or progression. Regardless of therapy, extramedullary disease was associated with shorter progression-free and overall survival, as well as the presence of anemia, thrombocytopenia, elevated serum lactate dehydrogenase, cytogenetic abnormalities, and high-risk features in 70-and 80-gene risk models in univariate analysis. Multivariate analysis with logistic regression revealed that this disease feature was more prevalent in patients with an elevated centrosome index, as determined by gene expression profiling, as well as in myeloma molecular subtypes that are more prone to relapse. These include the MF subtype (also called the “MAF” subtype, associated with over-expression of the MAF gene seen with chromosome translocation 14;16 or 14;20) and the PR subtype (also called the “Proliferation” subtype, associated with overexpression of pro-proliferative genes).

Conclusions

These data show that extramedullary disease is more prevalent in genomically defined high-risk multiple myeloma and is associated with shorter progression-free survival and overall survival, even in the era of novel agents. All clinical trials included in the analyses were registered with www.clinicaltrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT00083551","term_id":"NCT00083551"}}NCT00083551, {"type":"clinical-trial","attrs":{"text":"NCT00083876","term_id":"NCT00083876"}}NCT00083876, {"type":"clinical-trial","attrs":{"text":"NCT00081939","term_id":"NCT00081939"}}NCT00081939, {"type":"clinical-trial","attrs":{"text":"NCT00572169","term_id":"NCT00572169"}}NCT00572169, {"type":"clinical-trial","attrs":{"text":"NCT00644228","term_id":"NCT00644228"}}NCT00644228,{"type":"clinical-trial","attrs":{"text":"NCT00002548","term_id":"NCT00002548"}}NCT00002548,{"type":"clinical-trial","attrs":{"text":"NCT00734877","term_id":"NCT00734877"}}NCT00734877).Key words: extramedullary disease, transplant, myeloma, survival     

Perspectivity in Psychiatric Research: The Psychopathology of Schizophrenia in Postwar Germany (1955–1961)

The reorganization of psychiatric knowledge at the turn of the twentieth century derived from Emil Kraepelin’s clinical classification of psychoses. Surprisingly, within just few years, Kraepelin’s simple dichotomy between dementia praecox (schizophrenias) and manic-depressive psychosis (bipolar disorders) succeeded in giving psychiatry a new framework that is still used until the present day. Unexpectedly, Kraepelin’s simple clinical scheme based on the dichotomy replaced the significantly more differentiated nosography that dominated psychiatric research in the last three decades of the nineteenth century (Janzarik in Themen und Tendenzen der deutschsprachigen Psychiatrie. Springer, Berlin, 1974). Moreover, although all the components of the future development were already available shortly after 1868, the real course, which led to Kraepelin’s dichotomy, was unpredictable then. This paper explores the ways in which the unpredictability of psychiatric knowledge and the postulate of a rationality underlying psychopathological phenomena interacted in the debates regarding the classification of psychoses. It examines the “natural antagonism” between the practical aspirations of an increasingly specialized medical nosology and unitary conceptions, which, in a psychopathological countermovement, emphasized that no somatic criteria can be specified for the majority of psychic abnormalities and that all nosological distinctions are not binding (Janzarik 1974, 20). In this context, this paper investigates the revival of unitary theories of psychosis in postwar German psychiatry and seeks to understand why the forms of thinking that dominated nineteenth-century psychiatry have proved to be very lasting. Furthermore, this paper emphasizes the perspectivity underlying psychiatric research on psychoses and explores the ways in which writing the history of the schizophrenia concept involves inevitably writing the history of the entire psychiatry.     

Incorporating bortezomib into upfront treatment for multiple myeloma: early results of total therapy 3

Total therapy 3 incorporated bortezomib into a melphalan-based tandem transplant regimen for 303 newly diagnosed patients with myeloma. Induction chemotherapy prior to and consolidation chemotherapy after transplants each consisted of two cycles of VTD-PACE (bortezomib, thalidomide, dexamethasone and 4-d continuous infusions of cis-platin, doxorubicin, cyclophosphamide, etoposide); 3-year maintenance comprised monthly cycles of VTD in the first and TD in the remaining years. The median age was 59 years (age >64 years, 28%). A minimum of 20 x 10(6) CD34 cells/kg was collected in 87% of patients; 83% completed both transplants, and only 5% suffered a treatment-related death. At 24 months, 83% had achieved near-complete remission, which was sustained in 88% at 2 years from its onset. With a median follow-up of 20 months, 2-year estimates of event-free and overall survival were 84% and 86% respectively. The 44 patients who experienced an event more often had a high-risk gene array profile, cytogenetic abnormalities and indicators of high lactate dehydrogenase, beta-2-microglobulin, creatinine and International Staging System stage. Toxicities of grade > 2 included thrombo-embolic events in 27% and peripheral neuropathy in 12%. Results of this phase-2 study demonstrated that bortezomib could be safely combined with multi-agent chemotherapy, effecting near-complete remission status and 2-year survival rates in more than 80% of patients.