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Background: Available treatments for older patients with primary diffuse large B-cell CNS lymphoma (PCNSL) offer progression-free survival of up to 16 months. We aimed to investigate an intensified treatment of high-dose chemotherapy and autologous haematopoietic stem-cell transplantation (HSCT) in older patients with PCNSL., Methods: MARTA was a prospective, single-arm, phase 2 study done at 15 research hospitals in Germany. Patients aged 65 years or older with newly diagnosed, untreated PCNSL were enrolled if they had an Eastern Cooperative Oncology Group performance status of 0-2 and were fit for high-dose chemotherapy and autologous HSCT. Induction treatment consisted of two 21-day cycles of high-dose intravenous methotrexate 3·5 g/m 2 (day 1), intravenous cytarabine 2 g/m 2 twice daily (days 2 and 3), and intravenous rituximab 375 mg/m 2 (days 0 and 4) followed by high-dose chemotherapy with intravenous rituximab 375 mg/m 2 (day -8), intravenous busulfan 3·2 mg/kg (days -7 and -6), and intravenous thiotepa 5 mg/kg (days -5 and -4) plus autologous HSCT. The primary endpoint was progression-free survival at 12 months in all patients who met eligibility criteria and started treatment. The study was registered with the German clinical trial registry, DRKS00011932, and recruitment is complete., Findings: Between Nov 28, 2017, and Sept 16, 2020, 54 patients started induction treatment and 51 were included in the full analysis set. Median age was 71 years (IQR 68-75); 27 (53%) patients were female and 24 (47%) were male. At a median follow-up of 23·0 months (IQR 16·8-37·4), 23 (45%) of 51 patients progressed, relapsed, or died. 12-month progression-free survival was 58·8% (80% CI 48·9-68·2; 95% CI 44·1-70·9). During induction treatment, the most common grade 3-5 toxicities were thrombocytopenia and leukopenia (each in 52 [96%] of 54 patients). During high-dose chemotherapy and autologous HSCT, the most common grade 3-5 toxicity was leukopenia (37 [100%] of 37 patients). Treatment-related deaths were reported in three (6%) of 54 patients, all due to infectious complications., Interpretation: Although the primary efficacy threshold was not met, short induction followed by high-dose chemotherapy and autologous HSCT is active in selected older patients with PCNSL and could serve as a benchmark for comparative trials., Funding: Else Kröner-Fresenius Foundation, Riemser Pharma, and Medical Center-University of Freiburg., Competing Interests: Declaration of interests ES received research funding to her institution from the Else Kröner-Fresenius Foundation, Riemser Pharma, Roche Pharma, and Bundesministerium für Bildung und Forschung Germany; received honoraria for lectures from Riemser Pharma and SERB SAS Pharmaceuticals; is on the advisory board for SERB SAS Pharmaceuticals; and is an unpaid member of the steering committee of the German Lymphoma Alliance. AK received honoraria from Roche, Celgene, Sobi, AbbVie, Takeda, and Bristol Myers Squibb; and support for attending meetings or travel from AbbVie, BeiGene, ENSA Pharma, Sobi, and Takeda. ARö received honoraria from Alexion, Amgen, Apellis, Novartis, Roche, Sanofi, and Sobi, and support for attending meetings or travel from Sobi; and is on a data safety monitoring board or advisory board from Alexion, Amgen, Apellis, Novartis, Roche, Bioverativ, Sanofi, Sobi, and Samsung. BK received consulting fees from Dayton Therapeutics and Incyte and honoraria from Dayton Therapeutics, Incyte, and Roche. LP received travel support from Medac and Gilead. JW is an unpaid member of the steering committee of the German Lymphoma Alliance. FS received research funding from Roche Sequencing Solutions, Gilead, and Takeda, and honoraria from AstraZeneca. GIh is part of the data safety monitoring board for Novartis trials. EB-M and HF received institutional research funding from the Else Kröner-Fresenius Foundation and Riemser Pharma. AO received honoraria for presentation from SERB SAS Pharmaceuticals. JF received honoraria from Medac, Neovii, and Riemser; payment for expert testimony from Sanofi; and support for attending meetings or travel from Medac and Neovii. GIl received research funding from Bundesministerium für Bildung und Forschung Germany; honoraria from Roche, Gilead, and Incyte; support for attending meetings or travel from Roche, Janssen, and Lilly; and is on an advisory board for Miltenyi Biotec. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The purpose of this study is to follow up the dynamics of pure tone threshold and DPOAE amplitude changes induced by glycerol with reference to its activity in the inner ear. Selection was made among 38 patients with Meniere's disease for those having positive glycerol test. Pure-tone audiometry and DP-gram were performed in four series: as an initial examination before glycerol intake, 1, 2 and 3 h after. Audiometric changes formed distinct biphasal pattern at all frequencies between 250 and 4,000 Hz. The most dynamic pure tone threshold decrease occurred during the first hour. Between the first and second hour after glycerol ingestion there was a phase of no significant hearing changes. Further pure tone threshold decrease went on within the third hour reaching its top. Observing DPOAE changes, the highest DP amplitude growth occurred after the second and the third hour at DP-gram frequencies 2, 3 and 4 kHz. The fastest DP-amplitude increase was registered as well during the first hour after glycerol ingestion. In 11 persons with both audiometry and DPOAE positive glycerol test, parallel dynamics in the course of the glycerol test was observed. Biphasal glycerol test dynamics suggests the possibility of two mechanisms of glycerol activity in the inner ear.

Objective: The most probable place generating tinnitus in the auditory pathway is the outer hair cells (OHCs) inside the cochlea. Otoacoustic emissions are used to assess their activity. The objective of the investigation was to measure the features of distortion product otoacoustic emissions (DPOAE) in a group of tinnitus patients without hearing loss, estimate the diagnostic value of the parameters for the analysis of cochlear function in the patients, emphasizing those most useful in localizing tinnitus generators, and determine the hypothetical influence of hyperacusis and misophony on DPOAE parameters in tinnitus patients., Patients and Methods: The material consisted of 44 patients with tinnitus and without hearing loss. In the control group were 33 patients without tinnitus with the same state of hearing. The tinnitus patients were divided into three subgroups: those with hyperacusis, those with misophonia, and those with neither. After collecting medical history and performing clinical examination of all the patients, tonal and impedance audiometry, ABR, and discomfort level were evaluated. Then DPOAE were measured using three procedures. First the amplitudes of two points per octave were assessed, second the "fine structure" method with 16-20 points per octave (f2/f1=1.22, L1=L2=70 dB), and the third procedure included recording the growth function in three series for input tones of f2=2002, 4004, and 6006Hz (f2/f1=1.22) and L1=L2 levels increasing by increments of 5 dB in each series., Results and Conclusions: Hyperacusis was found in 63% and misophonia in 10% of the tinnitus patients with no hearing loss. DPOAE amplitudes in recordings with two points per octave and the fine structure method are very valuable parameters for estimating cochlear function in tinnitus patients with normal hearing. Function growth rate cannot be the only parameter in measuring DPOAE in tinnitus patients, including subjects with hyperacusis and misophonia. The markedly higher DPOAE amplitudes in the group of tinnitus patients without hearing loss suggest that tinnitus may be caused by increased motility of the OHCs induced by decreasing efferent fiber activity, and not by OHC failure. Hyperacusis significantly increases the amplitude of DPOAE in tinnitus patients with no hearing loss., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)