Acute onset of tinnitus in patients with sudden deafness

Objective: We made hypotheses that tinnitus will appear more likely in patients with sudden deafness with superior hearing in unaffected ear or with more severe acute hearing loss. Methods: A retrospective cohort study was performed. Five hundred forty-one patients were identified with idiopathic sudden sensorineural hearing loss (ISSHL) from January 1995 to August 2006. The exclusion criteria for this study were as follows: bilateral sudden hearing loss and Meniere disease, previous tinnitus or bilateral tinnitus at initial evaluation, and onset of hearing loss less than 7 days. The cohort enrolled 454 patients. The enrolled patients were classified into two groups: patient with acute onset tinnitus in the affected ear and patients without tinnitus at initial visit. Main outcome measures were patient age, the presence or absence of vertigo and tinnitus, audiometric patterns, the severity of hearing loss, and hearing in the unaffected ear. Results: Better contralateral hearing (n = 220 versus n = 72, P < 0.001) and younger age (48 versus 55 years, P < 0.001) were independently associated with the acute onset of tinnitus in patients with ISSHL. The degree of asymmetry between the ears did not differ significantly between patients with and without tinnitus. The sex, presence of vertigo, shape of audiogram, and severity of hearing loss were not correlated with tinnitus occurrence. Conclusions: Tinnitus triggered by ISSHL was more frequent in patients with better contralateral hearing and of a younger age, irrespective of the severity of hearing loss on the affected side or the asymmetry between the ears

PSMA-PET/CT-guided salvage radiotherapy in recurrent or persistent prostate cancer and PSA < 0.2 ng/ml.

PURPOSE The purpose of this retrospective, multicenter study was to assess efficacy of PSMA-PET/CT-guided salvage radiotherapy (sRT) in patients with recurrent or persistent PSA after primary surgery and PSA levels < 0.2 ng/ml. METHODS The study included patients from a pooled cohort (n = 1223) of 11 centers from 6 countries. Patients with PSA levels > 0.2 ng/ml prior to sRT or without sRT to the prostatic fossa were excluded. The primary study endpoint was biochemical recurrence-free survival (BRFS) and BR was defined as PSA nadir after sRT + 0.2 ng/ml. Cox regression analysis was performed to assess the impact of clinical parameters on BRFS. Recurrence patterns after sRT were analyzed. RESULTS The final cohort consisted of 273 patients; 78/273 (28.6%) and 48/273 (17.6%) patients had local or nodal recurrence on PET/CT. The most frequently applied sRT dose to the prostatic fossa was 66-70 Gy (n = 143/273, 52.4%). SRT to pelvic lymphatics was delivered in 87/273 (31.9%) patients and androgen deprivation therapy was given to 36/273 (13.2%) patients. After a median follow-up time of 31.1 months (IQR: 20-44), 60/273 (22%) patients had biochemical recurrence. The 2- and 3-year BRFS was 90.1% and 79.2%, respectively. The presence of seminal vesicle invasion in surgery (p = 0.019) and local recurrences in PET/CT (p = 0.039) had a significant impact on BR in multivariate analysis. In 16 patients, information on recurrence patterns on PSMA-PET/CT after sRT was available and one had recurrent disease inside the RT field. CONCLUSION This multicenter analysis suggests that implementation of PSMA-PET/CT imaging for sRT guidance might be of benefit for patients with very low PSA levels after surgery due to promising BRFS rates and a low number of relapses within the sRT field

The prognostic significance of a negative PSMA-PET scan prior to salvage radiotherapy following radical prostatectomy.

AIM The optimal management for early recurrent prostate cancer following radical prostatectomy (RP) in patients with negative prostate-specific membrane antigen positron-emission tomography (PSMA-PET) scan is an ongoing subject of debate. The aim of this study was to evaluate the outcome of salvage radiotherapy (SRT) in patients with biochemical recurrence with negative PSMA PET finding. METHODS This retrospective, multicenter (11 centers, 5 countries) analysis included patients who underwent SRT following biochemical recurrence (BR) of PC after RP without evidence of disease on PSMA-PET staging. Biochemical recurrence-free survival (bRFS), metastatic-free survival (MFS) and overall survival (OS) were assessed using Kaplan-Meier method. Multivariable Cox proportional hazards regression assessed predefined predictors of survival outcomes. RESULTS Three hundred patients were included, 253 (84.3%) received SRT to the prostate bed only, 46 (15.3%) additional elective pelvic nodal irradiation, respectively. Only 41 patients (13.7%) received concomitant androgen deprivation therapy (ADT). Median follow-up after SRT was 33 months (IQR: 20-46 months). Three-year bRFS, MFS, and OS following SRT were 73.9%, 87.8%, and 99.1%, respectively. Three-year bRFS was 77.5% and 48.3% for patients with PSA levels before PSMA-PET ≤ 0.5 ng/ml and > 0.5 ng/ml, respectively. Using univariate analysis, the International Society of Urological Pathology (ISUP) grade > 2 (p = 0.006), metastatic pelvic lymph nodes at surgery (p = 0.032), seminal vesicle involvement (p 0.5 ng/ml (p = 0.004), and lack of concomitant ADT (p = 0.023) were significantly associated with worse bRFS. On multivariate Cox proportional hazards, seminal vesicle infiltration (p = 0.007), ISUP score >2 (p = 0.048), and pre SRT PSA level > 0.5 ng/ml (p = 0.013) remained significantly associated with worse bRFS. CONCLUSION Favorable bRFS after SRT in patients with BR and negative PSMA-PET following RP was achieved. These data support the usage of early SRT for patients with negative PSMA-PET findings

Development and Validation of a Multi-institutional Nomogram of Outcomes for PSMA-PET-Based Salvage Radiotherapy for Recurrent Prostate Cancer.

IMPORTANCE Prostate-specific antigen membrane positron-emission tomography (PSMA-PET) is increasingly used to guide salvage radiotherapy (sRT) after radical prostatectomy for patients with recurrent or persistent prostate cancer. OBJECTIVE To develop and validate a nomogram for prediction of freedom from biochemical failure (FFBF) after PSMA-PET-based sRT. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study included 1029 patients with prostate cancer treated between July 1, 2013, and June 30, 2020, at 11 centers from 5 countries. The initial database consisted of 1221 patients. All patients had a PSMA-PET scan prior to sRT. Data were analyzed in November 2022. EXPOSURES Patients with a detectable post-radical prostatectomy prostate-specific antigen (PSA) level treated with sRT to the prostatic fossa with or without additional sRT to pelvic lymphatics or concurrent androgen deprivation therapy (ADT) were eligible. MAIN OUTCOMES AND MEASURES The FFBF rate was estimated, and a predictive nomogram was generated and validated. Biochemical relapse was defined as a PSA nadir of 0.2 ng/mL after sRT. RESULTS In the nomogram creation and validation process, 1029 patients (median age at sRT, 70 years [IQR, 64-74 years]) were included and further divided into a training set (n = 708), internal validation set (n = 271), and external outlier validation set (n = 50). The median follow-up was 32 months (IQR, 21-45 months). Based on the PSMA-PET scan prior to sRT, 437 patients (42.5%) had local recurrences and 313 patients (30.4%) had nodal recurrences. Pelvic lymphatics were electively irradiated for 395 patients (38.4%). All patients received sRT to the prostatic fossa: 103 (10.0%) received a dose of less than 66 Gy, 551 (53.5%) received a dose of 66 to 70 Gy, and 375 (36.5%) received a dose of more than 70 Gy. Androgen deprivation therapy was given to 325 (31.6%) patients. On multivariable Cox proportional hazards regression analysis, pre-sRT PSA level (hazard ratio [HR], 1.80 [95% CI, 1.41-2.31]), International Society of Urological Pathology grade in surgery specimen (grade 5 vs 1+2: HR, 2.39 [95% CI, 1.63-3.50], pT stage (pT3b+pT4 vs pT2: HR, 1.91 [95% CI, 1.39-2.67]), surgical margins (R0 vs R1+R2+Rx: HR, 0.60 [95% CI, 0.48-0.78]), ADT use (HR, 0.49 [95% CI, 0.37-0.65]), sRT dose (>70 vs ≤66 Gy: HR, 0.44 [95% CI, 0.29-0.67]), and nodal recurrence detected on PSMA-PET scans (HR, 1.42 [95% CI, 1.09-1.85]) were associated with FFBF. The mean (SD) nomogram concordance index for FFBF was 0.72 (0.06) for the internal validation cohort and 0.67 (0.11) in the external outlier validation cohort. CONCLUSIONS AND RELEVANCE This cohort study of patients with prostate cancer presents an internally and externally validated nomogram that estimated individual patient outcomes after PSMA-PET-guided sRT

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

A mechanism for eye position effects on spontaneous nystagmus

In acute stages of unilateral vestibular deficit, the imbalanced tonic activity on vestibular afferents evokes spontaneous nystagmus. The slow-phase velocity of this nystagmus varies with eye position, such that it is smaller when looking in the direction of slow-phases. The neural mechanism for this behavior is still not understood. Here, using a simple control system model, we show that plausible changes in the neural responses within the central vestibulo-ocular reflex pathway are adequate to cause eye position dependent effects in the nystagmus pattern. The proposed transformations in population response functions could happen immediately following a lesion and can be useful to stabilize gaze in part of the gaze field

A re-examination of the time constant of the oculomotor neural integrator in human

We studied the horizontal oculomotor neural integrator in healthy human subjects during gaze holding in darkness. We found large variability among subjects with respect to the estimated time constants and the integrator's null position. We also found that individual subjects could demonstrate significantly nonlinear drift velocities as a function of eye position. Nevertheless, a consistent trend did not emerge. Consequently, cross subject averaging eliminates idiosyncratic nonlinear patterns and the average can be approximated by a linear function inside the range that was tested

Constant severe imbalance following traumatic otoconial loss: a new explanation of residual dizziness

Benign paroxysmal positional vertigo (BPPV) is the most common type of vertigo, caused by otoconia falling from the utricle into a semicircular canal (SCC). After successful repositioning maneuvers residual dizziness (RD) has been described and several reasons are used to explain RD. It can last for only a few days or weeks, but also much longer. We present a patient with a severe traumatic loss of otoconia from both maculae utriculi and a persistent imbalance more than 9 years. We think that the loss of otoconia from the utricular and probably also saccular macula induced a sudden reduction of her ability to sense gravity thus logically explaining her symptoms. We show the vestibular test results also supporting our hypothesis and we extrapolate this support to other forms of so far unexplained dizziness especially increasing imbalance with aging. We also discuss the normal c- and oVEMP indicating intact haircell function and supporting our hypothesis of isolated otoconial loss as the major cause for imbalance