Search

Background The efficacy and safety of lenvatinib (LEN) are unknown in cases that were excluded in the phase III trial (REFLECT trial) of LEN, including those who experienced tyrosine kinase inhibitors (TKI) before LEN. In addition, no evidence has been established for early introduction of molecular targeted therapy in BCLC stage B patients. Therefore, we verified the efficacy and safety in the patients who did not meet the inclusion criteria of REFLECT trial and those who were BCLC Stage B. Methods A total of 203 patients received LEN from March 2018 to January 2019 at 21 sites in Japanese Red Cross Study Liver Group were registered. 128 cases out of REFLECT trial criteria and 74 cases of BCLC Stage B were retrospectively investigated. Tumors assessments in accordance with modified RECIST were done using dynamic CT and/or MRI. Results 128 of 203 (63%) patients did not meet the inclusion criteria of the REFLECT trial. These cases included 69 receiving TKI therapy before LEN. The ORR and DCR in TKI naive were 45% and 84%, respectively, and were 29% and 81% in TKI experienced (p = 0.072, p = 0.671). The OS between TKI naive and experienced patients was not significantly different (p = 0.618), even though baseline albumin level and ALBI score were significantly lower in TKI experienced patients than TKI naive (p = 0.001 and 0.005). 74 cases of BCLC Stage B included 57 with TACE history, 8 without, and 9 cases unknown. Although there was no difference between two groups in the baseline Child-Pugh score, ALBI score and AFP value, patients with TACE less than 6 times (n = 53) before LEN was significantly better in OS than those with TACE of 6 times or more (n = 12) (p = 0.025). Conclusions Also in TKI experienced which was excluded from the REFLECT trial, ORR, DCR and OS did not differ from TKI naive, and LEN may be useful as TKI 2nd line and 3rd line. In BCLC Stage B patients, TACE group less than 6 times has a better prognosis after LEN treatment compared with group more than 6 times, and an early introduction of LEN for multiple TACE cases may contribute to life prognosis improvement is there. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Das Auftreten toxischer Schaden am akustischen System — zentral wie peripher —, durch Streptomycinsulfat in 20facher therapeutischer Dosis verursacht, kann im Tierexperiment durch Losung des Streptomycins in Ozothin weitgehend gemindert und bei vorheriger i. m. Injektion von Ozothin sogar verhutet werden. Bei dem wesentlich ototoxischeren Neomycinsulfat kann durch Ozothin eine weitgehende, signifikante Minderung der ototoxischen Wirkung erreicht werden. Die „in vivo-Versuche” an mit drei Infektionsarten infizierten Mausen beweisen, das das Ozothin im Vergleich zum Aqua bidest. die biologische Aktivitat des Streptomycinsulfats weder abschwacht, noch verstarkt, also nicht beeinflust. Somit zeigen these Untersuchungsergebnisse eindeutig, das in der Klinik bei einer notwendigen Behandlung mit basischen Streptomyces-Antibiotica die Zugabe von Ozothin eine Verhutung ototoxischer Schaden ermoglichen und sogar eine Erhohung der Streptomycindosen — unter strenger audiologischer Kontrolle — wahrscheinlich werden lassen kann.

Die Mittelung zentraler akustischer Reizantworten aus dem EEG des wachen Menschen mit Computern zum. Zwecke der „Objektiven Audiometric” ergibt bei exakter Methodik eine sehr geringe Streubreite dieser akustischen Reizantworten beim normalhorenden Menschen. Die Fehlermoglichkeiten dieser Methodik werden ausfuhrlich dargestellt. Es wurde der Beweis erbracht, das signifikante Untersehiede im Cerebro-Audiogramm (CAG) bei Schwerhorigen im Vergleich zur Norm objektiv zu erfassen sind. Durch Aufstellen der Intensitats-funktionen, wie sie psychoakustisch von Stevens gewonnen wurden, konnen an Hand der „Reizstarken-Erregungs-Kennlinien” die Horschwelle, Adaptation und Lautheitsempfindungen (Hyperakusis, Recruitment usw.) beim horgeschadigten Menschen objektiv erfast und quantitativ beurteilt werden. Die Ergebnisse und Probleme der „Objektiven Audiometrie” bei Kindern werden dargestellt.

Homolateral efferent influence: An isolated, histologically verified damage of the nucleus cochlearis (degeneration of the ganglion cells) of guinea pigs, quantitatively dependent on an increased dose of Gentamicinsulfate, causes — if effected by ipsilateral acoustic stimulation — a significant diminution of the “slow evoked potentials” of the acoustic cortex and an increase of the “compound action potentials” of the acoustic nerve. By giving higher doses of Gentamicinsulfate, histologically a greater damage to the central auditory pathways and only a little damage of the hair cells of the organ of Corti was to be found and thereby we registered greater diminution of the “slow evoked potentials” of the acoustic cortex and little decrease of the “cochlear microphonics”, but further increase of the “compound action potentials” of the acoustic nerve. The loss of inhibition of the central auditory pathways of the cochlea only influenced the “compound action potentials” of the acoustic nerve, but not the “coch...

THOUGH many new antibiotics have been found, the streptomycin series have not lost their importance. They are still one of the most effective remedies for all forms of tuberculosis. However, the use of streptomycin is limited by its additional neurotoxical and ototoxical affects. Such accompaniments were first described by Brown and Hinshaw.1Since then, a great many clinical and experimental papers concerning the ototoxicity of basic streptomyces-antibiotics have been published.2-9 Electrophysiological experiments of Stange et al9concerning the efficiency of streptomycin-sulfate on excitation and adaptation of the hair-cells in the organ of Corti, especially, proved that streptomycin injures the metabolism of the sensory cells in the ear. It affects the cellular membrane and restricts its reabsorption.5The result is an accumulation of streptomycin in the sensory cells and, consequently, loss of function. Experiments to reduce the ototoxic effect of streptomycin have been made for several years.