Immunomodulatory treatment for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma)

The pathogenesis of mucosa-associated lymphoid tissue (MALT) lymphoma has been characterized as a dynamic process driven by lymphoma cell dependency on T-cell signaling, chronic antigenic stimulation of marginal zone B-cells and activation of the nuclear factor-kappa B signaling pathway. This concept is underlined by the strong causal connection of chronic Helicobacter pylori associated gastritis and MALT lymphoma development based on perpetual auto-antigenic stimulation of Helicobacter pylori-specific T-cells, but also its association with further potential infectious triggers and autoimmune disorders for extragastric lymphoma sites. Thus, given the dependency of MALT lymphoma cells on the tumor microenvironment, this specific entity appears highly suitable for immunomodulatory treatment strategies. Several approaches have been assessed in the last years including promising data on immunomodulatory agents “IMiDs” thalidomide and lenalidomide, macrolide antibiotics and antibodies. The aim of the present review is to discuss rationales for immunomodulatory therapies in MALT lymphoma and to present the statu quo on immunomodulatory and therefore chemotherapy-free treatment strategies for these patients.     

A Phase Ib/II,open-label,multicenter study of INC280 (capmatinib) alone and in combination with buparlisib (BKM120) in adult patients with recurrent glioblastoma

Journal of Neuro-Oncology - To estimate the maximum tolerated dose (MTD) and/or identify the recommended Phase II dose (RP2D) for combined INC280 and buparlisib in patients with recurrent...     

Simulation of the Peritectic Phase Transition in Fe-C Alloys

In this work, a multi-phase cellular automaton (CA) model is extended for the quantitative simulation of peritectic phase transition. First, the effects of cooling rate/supersaturation and temperature on the peritectic transformation kinetics in Fe-C alloys are investigated by utilizing the present CA model. The CA simulations show that supersaturations in the parent phases (liquid and δ-ferrite) increase the L/γ interface growth velocity remarkably, but tinily for the δ/γ interface migration velocity. There exists a transition supersaturation for isothermal transformations, at which the growth rates of the two interfaces are equal. The transition supersaturation is found to increase with decreasing temperature. Microstructural evolution at different cooling rates during peritectic transformation is simulated using the experimental conditions. At low cooling rates, the δ/γ interface propagates at a higher velocity than the L/γ interface. At high cooling rates, however, the γ-phase grows more into the L-phase with a cellular morphology. Then, the proposed CA model is applied to simulate the microstructural evolution during peritectic reaction. It is observed that the γ-phase propagates along the L/δ interface and finally encircles the δ-phase. Meanwhile, the intervenient γ-phase grows in thickness through peritectic transformation. The CA simulations are compared reasonably well with the experimental data and analytical calculations.     

Mucociliary function of the eustachian tube in the eustachian tube dysfunction

Background: Most of the tests to evaluate the eustachian tube (ET) function are focused on the ventilation function of the ET.

Aim: Here we evaluate mucociliary function of the ET in patients with ET dysfunction.

Materials and methods: Ten patients with ET dysfunction were enrolled into the study. Six patients had chronic tympanic membrane retraction and four patients had chronic middle ear effusion (MEE). All patients had intact tympanic membranes. Tympanometry and clinical examinations were done to all patients. Mucociliary function was evaluated with technetium labeled albumin and blue dye. Tympanometry and clinical examinations were done to six patients with chronic tympanic membrane retraction and four patients with chronic middle ear effusion (MEE). Mucociliary function of the ET was evaluated with technetium labeled albumin and blue dye placed into middle ear through an intact tympanic membrane and followed from nasopharynx ET orifice (blue dye) and with gamma camera (technetium).

Results: Blue dye was observed in tubal orifice in six (6 of 10) patients during 30?min observation. Five of those patients (5 of 6) had tympanic membrane retraction and one patient (1 of 6) had MEE. Tracer activity decreased from middle ear in six (6 of 10) patients. Four of those patients had tympanic membrane retraction and two had MEE.

Conclusion: Mucociliary function of the ET seems to be better in patients with tympanic membrane retraction than patients with middle ear effusion.

Significance: Mucociliary function of the ET is an important function for middle ear aeration, blue dye test is easily available to be used also in clinical practice.     

mGluR5 and GABAA receptor‐specific parametric PET atlas construction—PET/MR data processing pipeline,validation, and application

The glutamate and γ‐aminobutyric acid neuroreceptor subtypes mGluR₅ and GABA_A are hypothesized to be involved in the development of a variety of psychiatric diseases. However, detailed information relating to their in vivo distribution is generally unavailable. Maps of such distributions could potentially aid clinical studies by providing a reference for the normal distribution of neuroreceptors and may also be useful as covariates in advanced functional magnetic resonance imaging (MR) studies. In this study, we propose a comprehensive processing pipeline for the construction of standard space, in vivo distributions of non‐displaceable binding potential (BP _ND), and total distribution volume (V _T) based on simultaneously acquired bolus‐infusion positron emission tomography (PET) and MR data. The pipeline was applied to [¹¹C]ABP688‐PET/MR (13 healthy male non‐smokers, 26.6 ± 7.0 years) and [¹¹C]Flumazenil‐PET/MR (10 healthy males, 25.8 ± 3.0 years) data. Activity concentration templates, as well as V _T and BP _ND atlases of mGluR₅ and GABA_A, were generated from these data. The maps were validated by assessing the percent error δ from warped space to native space in a selection of brain regions. We verified that the average δ_ABP = 3.0 ± 1.0% and δ_FMZ = 3.8 ± 1.4% were lower than the expected variabilities σ of the tracers (σ_ABP = 4.0%–16.0%, σ_FMZ = 3.9%–9.5%). An evaluation of PET‐to‐PET registrations based on the new maps showed higher registration accuracy compared to registrations based on the commonly used [¹⁵O]H₂O‐template distributed with SPM12. Thus, we conclude that the resulting maps can be used for further research and the proposed pipeline is a viable tool for the construction of standardized PET data distributions.     

Evaluation of neurotoxicity induced by paclitaxel second-line chemotherapy

 The most important cytotoxic drugs for the treatment of ovarian cancer, platinum compounds and paclitaxel, are known to induce neurotoxicity, which is dose limiting when higher paclitaxel doses are used or platinum-pretreated patients are treated. The absolute dose of paclitaxel per course has been demonstrated to be an important risk factor for the development of neurotoxicity. The role of cumulative dose, treatment duration and infusion schedule as additional risk factors are still in debate, and are therefore evaluated in this study. This study evaluates paclitaxel induced neurotoxicity in 38 patients, most of whom had already received platinum treatment, receiving either 135 or 175 mg/m² as 3-h or 24-h infusion. Patients were compared with an age-matched control group. A detailed questionnaire and neurophysiological measurements including vibration perception threshold were used. Overall, the majority of patients (76%) developed some degree of neurotoxicity, but symptoms were usually mild or moderate with no grade 3/4 neurotoxicity observed. Age has been demonstrated to be an important risk factor for the development of neurotoxicity. Furthermore, the higher dose per course showed a significant impact on neurotoxicity, while the different infusion schedules were of minor importance. Vibration threshold perception, 2-point discrimination, a walking-the-line test, and reports of paresthesias were shown to be the most sensitive and useful parameters for neurotoxicity evaluation. Neurotoxicity is a common adverse event during paclitaxel chemotherapy in platinum-pretreated patients. A clinically useful test panel composed of a detailed history and the above three easily performed neurophysiological evaluations should be incorporated into future studies evaluating new drugs, treatment modifications, new combinations, and potential modulators of chemotherapy-induced neurotoxicity. Published online: 22 July 1999     

Acute management and outcome of multiple trauma patients with pelvic disruptions

ABSTRACT: INTRODUCTION: Data on pre-hospital and trauma room fluid management of multiple trauma patients with pelvic disruptions are rarely reported. Present trauma algorithms recommend early haemorrhage control and massive fluid resuscitation. By matching the German Pelvic Injury Register (PIR) with the TraumaRegister DGU(R) (TR) for the first time, we attempt to assess the initial fluid management for different Tile/OTA types of pelvic ring fractures. Special attention was given to the patient's post traumatic course, particularly ICU data and patient outcome. METHODS: A specific match code was applied to identify certain patients with pelvic disruptions from both PIR and TR anonymous trauma databases, admitted between 2004 and 2009. From the resulting intersection set, a retrospective analysis was done of pre-hospital and trauma room data, length of ICU stay, days of ventilation, incidence of multiple organ dysfunction syndrome (MODS), sepsis, and mortality. RESULTS: In total 402 patients were identified. Mean ISS was 25.9 points and the mean ratio of patients with ISS [greater than or equal to]16 was 85.6%. The fracture distribution was as follows: 19.7% type A, 29.4% type B, 36.6% type C, and 14.3% isolated acetabular and/or sacrum fractures. The type B/C, compared with type A fractures, were related to constantly worse vital signs that necessitated a higher volume of fluid and blood administration in the pre-hospital and/or the trauma room setting. This group of B/C fractures were also related to a significantly higher presence of concomitant injuries and related with increased ISS. This was related to increased ventilation and ICU stay, increased rate of MODS, sepsis and increased rate of mortality at least for the type C fractures. Approximately 80% of the deceased had sustained type B/C fractures. CONCLUSIONS: The present study confirms the actuality of traditional trauma algorithms with initial massive fluid resuscitation in the recent therapy of multiple trauma patients with pelvic disruptions. Low volume resuscitation seems not yet accepted in practice in managing this special patient entity. Mechanically unstable pelvic ring fractures type B/C (according Tile's/OTA classification) form a distinct entity that has to be considered notably in future trauma algorithms.