Cannabis-Induced Anxiety Disorder in the Emergency Department.

Background: In December 2018, Michigan became the 10th state to legalize marijuana for adults. Since this law took effect, increased availability and use of cannabis in Michigan have led to increased emergency department (ED) visits associated with the drug's psychiatric effects.

Objectives: To describe cannabis-induced anxiety disorder's prevalence, clinical features, and disposition in a community-based study.

Prognostic model for newly diagnosed CLL patients in Binet stage A: results of the multicenter, prospective CLL1 trial of the German CLL study group.

The heterogeneity of early stage CLL challenges prognostication, and refinement of prognostic indices for risk-adapted management in this population is essential. The aim of the multicenter, prospective CLL1 trial was to explore a novel prognostic model (CLL1-PM) developed to identify risk groups, separating patients with favorable from others with dismal prognosis. A cohort of 539 clinically, biochemically, and genetically characterized Binet stage A patients were observed until progression, first-line treatment, or death.

Prehospital amputation: An experimental comparison of techniques.

Objective: Prehospital limb amputation is a rare but potentially life-saving intervention. When patients cannot be extricated due to limb entrapment or have hemodynamic compromise that precludes a prolonged extrication, they may benefit from an emergent prehospital amputation. The objective was to experimentally compare three prehospital amputation techniques on porcine legs.

Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial.

Autologous transplantation is controversial for older patients with multiple myeloma. The role of age-adjusted high-dose melphalan and the impact of induction chemotherapy cycles is still unclear. A total of 434 patients aged 60-70 years were randomly assigned to 4 cycles of standard anthracycline-based induction chemotherapy or no induction.

Granulocyte-colony stimulating factor response is superior to neutropenia duration in predicting the risk of infection after high-dose chemotherapy for myeloma and lymphoma.

The patient granulocyte-colony stimulating factor (G-CSF) response is represented by the leukocyte peak in the blood induced by a single dose of G-CSF after chemotherapy, and is correlated with subsequent neutropenic infection risk. General patterns for a meaningful risk group stratification, have not yet been determined. Two independent data sets including a total of 306 cases with myeloma or lymphoma and autologous blood stem cell transplant were available.

Low temperature delays timing and enhances the cost of nitrogen fixation in the unicellular cyanobacterium Cyanothece.

Marine nitrogen-fixing cyanobacteria are largely confined to the tropical and subtropical ocean. It has been argued that their global biogeographical distribution reflects the physiologically feasible temperature range at which they can perform nitrogen fixation. In this study we refine this line of argumentation for the globally important group of unicellular diazotrophic cyanobacteria, and pose the following two hypotheses: (i) nitrogen fixation is limited by nitrogenase activity at low temperature and by oxygen diffusion at high temperature, which is manifested by a shift from strong to weak temperature dependence of nitrogenase activity, and (ii) high respiration rates are required to maintain very low levels of oxygen for nitrogenase, which results in enhanced respiratory cost per molecule of fixed nitrogen at low temperature.

Extramedullary multiple myeloma presenting as a pituitary mass lesion.

Introduction: A plasmocytoma involving the pituitary gland is an extremely rare entity, with approximately 22 cases of solitary myeloma or multiple myeloma presenting with sellar mass reported in the literature so far.

Case Report: Here, we report the case of a 71-year-old female patient affected by an extramedullary IgG-lambda multiple myeloma presenting as a pituitary mass lesion. We summarize the diagnostic approaches that confirmed the diagnosis of multiple myeloma and describe treatment outcome after therapy.

Dendritic cell-based vaccination of patients with advanced pancreatic carcinoma: results of a pilot study.

Background And Aims: Dendritic cell (DC)-based vaccination can induce antitumor T cell responses in vivo. This clinical pilot study examined feasibility and outcome of DC-based tumor vaccination for patients with advanced pancreatic adenocarcinoma.

Methods: Tumor lysate of patients with pancreatic carcinoma was generated by repeated freeze-thaw cycles of surgically obtained tissue specimens.

Bortezomib retreatment in relapsed multiple myeloma - results from a retrospective multicentre survey in Germany and Switzerland.

Objectives: This multicenter, retrospective survey evaluated the efficacy and safety of bortezomib retreatment in patients with relapsed multiple myeloma who had responded to initial bortezomib treatment.

Methods: Clinical records of 94 patients receiving bortezomib retreatment in Germany and Switzerland were reviewed.

Results: Sixty patients were included according to prespecified criteria.

Testing G-CSF responsiveness predicts the individual susceptibility to infection and consecutive treatment in recipients of high-dose chemotherapy.

The individual risk of infection and requirements for medical treatment after high-dose chemotherapy have been unpredictable. In this prospective, multicenter, open-label study we investigated the potential of granulocyte colony-stimulating factor (G-CSF) responsiveness as a predictor. A total of 168 patients with multiple myeloma or lymphoma received a single dose of subcutaneous G-CSF (lenograstim, 263 μg) after high-dose chemotherapy.

First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia.

Although chronic lymphocytic leukemia (CLL) is a disease of elderly patients, subjects older than 65 years are heavily underrepresented in clinical trials. The German CLL study group (GCLLSG) initiated a multicenter phase III trial for CLL patients older than 65 years comparing first-line therapy with fludarabine with chlorambucil. A total of 193 patients with a median age of 70 years were randomized to receive fludarabine (25 mg/m(2) for 5 days intravenously, every 28 days, for 6 courses) or chlorambucil (0.

Helper T cells (CD3 + /CD4 + ) within the autologous peripheral blood stem cell graft positively correlate with event free survival of multiple myeloma patients.

Background: The microenvironment in the bone marrow - including lymphocytes - is part of the pathophysiology of multiple myeloma (MM). High dose chemotherapy followed by autologous stem cell transplantation is standard of care for younger patients.

Aim: To determine the influence of reinfused lymphocyte subsets on event free survival (EFS) and overall survival (OS).

Inhibition of lymphocyte function associated antigen 1 by LFA878 induces apoptosis in multiple myeloma cells and is associated with downregulation of the focal adhesion kinase/phosphatidylinositol 3 kinase/Akt pathway.

Multiple myeloma (MM) is still an incurable disease and adhesion of MM cells to bone marrow stromal cells is one of the hallmarks of the disease. Lymphocyte function associated antigen 1 (LFA-1) is an adhesion molecule that mediates lymphocyte adhesion, but its role in MM is only poorly understood. The aim of the presented study was to improve knowledge on LFA-1 and associated pathways in MM for the development of molecular targeted therapies.

Activation of adenosine monophosphate activated protein kinase inhibits growth of multiple myeloma cells.

The role of adenosine monophosphate activated protein kinase (AMPK) in regulating multiple myeloma (MM) cell growth is not yet clear. In this study, we show that the AMPK activators 5-aminoimidazole-4-carboxamide riboside (AICAr) and D942 inhibit cell growth in MM cell lines. AICAr also induced an S-phase cell cycle arrest in all four tested cell lines and led to phosphorylation and thus activation of AMPK.

Selective induction of apoptosis in leukemic B-lymphoid cells by a CD19-specific TRAIL fusion protein.

Although the treatment outcome of lymphoid malignancies has improved in recent years by the introduction of transplantation and antibody-based therapeutics, relapse remains a major problem. Therefore, new therapeutic options are urgently needed. One promising approach is the selective activation of apoptosis in tumor cells by the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL).

First clinical experience with simvastatin to overcome drug resistance in refractory multiple myeloma.

In vitro statins overcome cell adhesion-mediated drug resistance at non-toxic concentrations that are achievable in humans by standard dose simvastatin. A pilot phase-II trial was initiated to determine feasibility and antimyeloma efficacy. In six myeloma patients refractory to two cycles of bortezomib or bendamustine simvastatin was concomitantly administered during further two cycles.

Bendamustine induces G2 cell cycle arrest and apoptosis in myeloma cells: the role of ATM-Chk2-Cdc25A and ATM-p53-p21-pathways.

Purpose: Multiple myeloma is a fatal hematological disease caused by malignant transformation of plasma cells. Bendamustine has been proven to be a potent alternative to melphalan in phase 3 studies, yet its molecular mode of action is still poorly understood.

Methods: The four-myeloma cell lines NCI-H929, OPM-2, RPMI-8226, and U266 were cultured in vitro.

A CD19-specific single-chain immunotoxin mediates potent apoptosis of B-lineage leukemic cells.

CD19 is a B-lineage-specific transmembrane signaling protein participating in the control of proliferation and differentiation. It is present at high surface density on chronic B-lymphocytic leukemia (B-CLL) cells and cells of other B-cell malignancies, and is a prime target for therapy with antibody-derived agents. Many attempts have been made to target malignant cells via CD19, but to date none of these agents have received drug approval.

Inhibition of adenosine monophosphate-activated protein kinase induces apoptosis in multiple myeloma cells.

In this study, we show that adenosine monophosphate-activated protein kinase (AMPK) is expressed and activated in multiple myeloma cells. The inhibition of AMPK induced growth arrest and reduction of cell viability in the cell viability assay using the water-soluble tetrazolium salt 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1 assay). Induction of apoptosis was determined by annexin-V and propidium iodide staining.

Evidence for cell adhesion-mediated drug resistance of multiple myeloma cells in vivo.

Background/aims: Multiple myeloma is an incurable disease and patients eventually die of disease progression due to drug resistance. VLA-4 (very late antigen 4), VCAM (vascular adhesion molecule), LFA-1 (leukocyte function-associated antigen 1), and ICAM-1 (intercellular adhesion molecule 1)-mediated adhesion of myeloma cells to bone marrow stromal cells induces primary multidrug resistance in vitro. Based on these preclinical data we hypothesized that myeloma cells with strong adhesion - due to strong expression of adhesion molecules on the cell surface - are selected by chemotherapy in patients.