Poor Mobilizers in Lymphoma but Not Myeloma Patients Had Significantly Poorer Progression-Free Survival after Autologous Stem Cell Transplantation: Results of a Large Retrospective, Single-Center Observational Study.

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 106 CD34+ cells/kg in lymphoma and ≥4.0 × 106 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies.

Changing Landscape in the Treatment of Adult Acute Lymphoblastic Leukemia (ALL).

Acute lymphoblastic leukemia (ALL) is a rare hematological malignancy characterized by proliferation and accumulation of premature lymphoid blasts. Depending on risk factors, the survival of acute lymphoblastic leukemia has significantly improved over the last decades. During the last years, measurable residual disease (MRD) assessment has evolved into one of the most sensitive markers for prognosis and risk of relapse. For this reason, measurable residual disease detection and monitoring count as standard evaluation in patients with acute lymphoblastic leukemia. Allogeneic stem cell transplantation is still the recommended treatment option for patients with high and highest risk profiles as well as for relapsed or refractory settings. The increased understanding of the pathomechanism and heterogeneity of acute lymphoblastic leukemia has led to the development of several novel therapeutic opportunities such as tyrosine-kinase inhibitors, antibody-based therapies and CAR-T cells with the aim of improving clinical outcomes. Furthermore, the major advances in disease understanding of ALL have led to the identification of different subgroups and better disease stratification. Even though novel therapy targets are constantly developed, acute lymphoblastic leukemia remains a challenging and life-threatening disease. To improve the historically unsatisfying result in therapy of adult acute lymphoblastic leukemia many clinical trials have recently been initiated to determine the optimum combination regimens of novel and old agents for adult acute lymphoblastic leukemia.

The Agony of Choice-Where to Place the Wave of BCMA-Targeted Therapies in the Multiple Myeloma Treatment Puzzle in 2022 and Beyond.

Since the introduction of first-generation proteasome inhibitors and immunomodulatory agents, the multiple myeloma (MM) treatment landscape has undergone a remarkable development. Most recently, immunotherapeutic strategies targeting the B cell maturation antigen (BCMA) entered the clinical stage providing access to highly anticipated novel treatment strategies. At present, numerous different approaches investigate BCMA as an effective multi-modal target. Currently, BCMA-directed antibody-drug conjugates, bispecific and trispecific antibodies, autologous and allogeneic CAR-T cell as well as CAR-NK cell constructs are either approved or in different stages of clinical and preclinical development for the treatment of MM. This armamentarium of treatment choices raises several challenges for clinical decision making, particularly in the absence of head-to-head comparisons. In this review, we provide a comprehensive overview of BCMA-targeting therapeutics, deliver latest updates on clinical trial data, and focus on potential patient selection criteria for different BCMA-targeting immunotherapeutic strategies.

[Drug interactions in emergency medicine]. / Medikamenteninteraktionen--In der Notfallmedizin.

Drug interactions in emergency medicine can occur in many forms and can result in different complications. Drug interactions can be the primary cause for the emergency call, but also they can happen after the application of different drugs at the scene. Emergency physicians need to be aware of possible interactions of their own emergency drugs. Additionally, interactions of different medications prescribed by physicians, non-prescription drugs and also by food are possible. Emergency drugs should never be mixed in a single syringe or applied together in a single infusion bag. Solving of medications always needs to be in accordance with the official instruction leaflet.

[Percutaneous tracheostomy in intensive care medicine - Update 2012]. / Punktionstracheotomie in der Intensivmedizin - Update 2012.

Percutaneous tracheostomy has become an established procedure in airway management of critically ill patients. It offers advantages over prolonged tracheal intubation. To date, there is no evidence of the optimal timing of the procedure. The Ciaglia Blue Rhino technique is the most common technique and, as any other techniques of percutaneous tracheostomy, is performed under general anaesthesia and with continuous bronchoscopic control. The recently introduced Ciaglia Blue Dolphin technique is based on radial dilatation with a fluid-filled high pressure balloon. Provided that specific contraindications are observed (e.g. difficult tracheal intubation, inability to identify anatomic landmarks, severe coagulopathy etc.), all techniques have low complication rates. The use of ultrasound may further enhance perioperative safety. Finally it must be noted that percutaneous tracheostomy is an elective procedure that requires informed consent from the patient or an attorney of law.

Comparative quality analysis of hands-off time in simulated basic and advanced life support following European Resuscitation Council 2000 and 2005 guidelines.

AIM: To compare hands-off time (HOT) in simulated advanced life support (ALS) following European Resuscitation Council (ERC) 2005 guidelines and ERC 2000 and to provide quantitative data on workflow. SUBJECTS AND METHODS: Observations with 18 professional paramedics, performing 39 megacodes (mega-code training; MCT) were videotaped during ALS re-certification. Teams were randomly assigned to train according to ERC 2000 or ERC 2005. HOT, hands-off intervals (HOI) and other variables describing interventions and workflow were analysed. RESULTS: In group ERC 2000 17±3 HOI appeared with a mean duration of 17.5±10.8 s (mean±SD). Overall HOT was 382±47 s, equivalent to a mean hands-off fraction (HOF) of 0.45±0.05. 15±5 ventilation-free intervals (VFI) were observed, with a mean duration of 21±10 s. In contrast after ERC 2005 variables resulted in 18±3 HOI with a mean duration of 10.0±4.0 s (p<0.001 vs ERC 2000), overall HOT 196±33 s (HOF 0.23±0.04; p<0.001), 24±12 VFI with a duration of 24±7 s (p<0.05). The first HOI lasted for 60.4±33.1 s in ERC 2000 and 17.6±4.3 s in ERC 2005 (p<0.001). In ERC 2000 6.1±2.6 interruptions for two bag/mask ventilations (BMV) lasted for 5.4±0.8 s, whereas in ERC 2005 9.6±3.1 interruptions for two BMV took 6.5±2.2 s (p<0.001). In both groups HOI were used thoroughly for basic life support/ALS-based interventions. CONCLUSION: The application of ERC guidelines of 2005 markedly reduced the first HOI and mean duration of HOI at the cost of delayed secure airway management and ECG analysis in this MCT model.

Effects of the selective cyclooxygenase-2 inhibitor rofecoxib on cell death following traumatic brain injury in the rat.

PURPOSE: Lateral fluid percussion brain injury (FPI) increases cyclooxygenase-2 (COX-2) expression in the cortex and hippocampus. The objective was to investigate whether the selective COX-2 inhibitor rofecoxib (10 mg/kg twice daily) reduces neuronal cell death after FPI in rats, since rofecoxib has been shown to be neuroprotective in other models of CNS injury. METHODS: Rofecoxib (n = 23) or vehicle (n = 20) were administered after FPI and for up to 3 days. Cell death was evaluated by Fluoro-Jade B staining and by the TdT-mediated dUTP nick end labelling (TUNEL) assay. RESULTS: COX-2 immunoreactivity increased in the ipsilateral cortex and hippocampus (CA1) and bilaterally in the dentate gyri. Fluoro-Jade B- and TUNEL-positive cells were detected 12-72 h after FPI in the ipsilateral cortex and bilaterally in the dentate gyri. Fluoro-Jade B staining did not indicate a significant neuroprotective effect of rofecoxib (12-72 h) and neither did TUNEL staining. Quantificaton of the TUNEL staining in the ipsilateral cortex was approximately 50% lower in the rofecoxib group at 12 and 24 h, but this did not reach statistical significance (p = 0.06), and appeared unchanged at 72 h. CONCLUSIONS: Rofecoxib lacked significant protective effect on early neuronal cell death in the FPI model of traumatic brain injury.

Assessment of the effects of the cyclooxygenase-2 inhibitor rofecoxib on visuospatial learning and hippocampal cell death following kainate-induced seizures in the rat.

Kainate-induced seizures result in hippocampal neurodegeneration and spatial learning deficits in rodents. Previous studies show that rofecoxib, a selective cyclooxygenase-2 inhibitor, protects against kainate-induced hippocampal cell death 3 days after seizures. Our aim was to determine whether rofecoxib attenuates visuospatial learning deficits and late neuronal death after kainate-induced seizures. Seizures were induced in Sprague-Dawley rats with kainic acid (10 mg/kg, i.p.). Eight hours later, animals received rofecoxib (10 mg/kg; n = 15) or vehicle (dimethylsulfoxide, n = 11). Animals were then treated daily for additional 2 or 9 days. Visuospatial learning was assessed in the Morris water maze (MWM) on days 5-9 after seizures. Seizure animals learned the MWM task significantly slower than non-seizure controls, but seizure animals showed higher swim speed (P < 0.05). Seizure animals receiving rofecoxib for 2 days showed no significant improvement in acquisition of the task compared to the vehicle group, even though mean latencies in the rofecoxib group were shorter from the third trial day onwards. This tendency was lost when rofecoxib was given for 9 days. TdT-mediated dUTP nick end labelling showed cell death in limbic structures 9 days after seizures. The time course of kainate-induced hippocampal cell death might be delayed by rofecoxib treatment, as the attenuation of cell death observed 3 days after seizures was no longer present after 9 days. We conclude that even though increasing evidence points to an injurious role of cyclooxygenase-2 products in acute brain injury processes, rofecoxib treatment failed to attenuate seizure-induced visuospatial learning deficits and the late phase of hippocampal neurodegeneration.

Cyclooxygenase-2, prostaglandin synthases, and prostaglandin H2 metabolism in traumatic brain injury in the rat.

Inflammatory mediators are important in traumatic brain injury (TBI). The objective of the present study was to investigate the expression of cyclooxygenase-2 (COX-2), prostaglandin E (PGE) and PGD synthases, and PGH2 metabolism in two rat models of TBI. Fluid percussion injury (FPI) resulted in bilateral induction of COX-2 mRNA in the dentate gyri and the cortex, whereas controlled cortical contusion injury (CCC) induced COX-2 mRNA in the ipsilateral dentate gyrus and intensely in the cortex as judged by in situ hybridization. The induction subsided within 24 h. COX-2 immunoreactivity was detectable in these areas and persisted in the ipsilateral cortex for at least 72 h after CCC. Regions with COX-2 induction co-localized with TUNEL staining, suggesting a link between COX-2 expression and cell damage. COX-2 forms PGH2, which can be isomerized to PGD2, PGE2, and PGF2alpha by enzymatic and non-enzymatic mechanisms. In situ hybridization showed that mRNA of PGD synthase and microsomal PGE synthase were present in the choroid plexus. The microsomal PGE synthase was induced bilaterally after FPI and unilaterally after CCC. Liquid chromatography-mass spectrometry showed that low speed supernatant of normal and traumatized cortex and hippocampus transformed PGH2 to PGD2 as main product. PGD2 was dehydrated in brain homogenates to biological active compounds, for example, 15-deoxy-delta12,14-PGJ2. Thus COX-2 increases in certain neurons following TBI without neuronal induction of PGD and microsomal PGE synthases, suggesting that PGH2 may decompose to PGD2 and its dehydration products by nonenzymatic mechanisms or to PGD2 by low constitutive levels of PGD synthase.