Prognostic value of pretherapeutic 68Ga-PSMA-11-PET based imaging parameters in mCRPC patients treated with PSMA radioligands.

PURPOSE: This study aims to evaluate the prognostic significance of various previously reported PSMA-PET parameters in patients undergoing 177Lu-PSMA radioligand therapy (RLT). While individual studies have investigated the prognostic value of one or few of these factors, comprehensive analyses are rare. METHODS: Data of 82 patients undergoing 177Lu-PSMA-radiologand-therapy (RLT) were analyzed. Total tumor volume (tumor volume), average SUVmean of all tumor lesions (SUVmean) and the quotient of sum of SUVmean of all tumor lesions to SUVmean of the parotid glands (tumor-parotid-ratio; TPR) and of the kidneys (tumor-kidney-ratio; TKR) were included in analysis. RESULTS: This study showed that a tumor volume of <290.6 ml is associated with a better survival in patients undergoing PSMA-RLT (median PFS: 4.2, median OS: 13.2 months) compared to patients with higher tumor volume (median PFS: 3.4,median OS: 6.2 months; p-value = 0.01 for PFS and <0.001 for OS). The average SUVmean correlated inversely with survival. Patients with a SUVmean > 10.7 had a median PFS of 4.2 and OS of 11.4 months while patients with SUVmean <10.7 had a median PFS of 1.6 and OS of 5 months (p-value <0.001 for both). The assessment of TPR showed no significant difference regarding OS and PFS. TKR showed a better PFS in patients with ratio > 0.33 (p-value 0.009) but no significant difference regarding OS. CONCLUSION: The present study confirms that pretherapeutic PSMA-PET before RLT with 177Lu-PSMA has a prognostic value.

A Prognostic Risk Score for Prostate Cancer Based on PSMA PET-derived Organ-specific Tumor Volumes.

Background Prostate-specific membrane antigen (PSMA) PET has high specificity in localizing primary tumors and metastases in patients with prostate cancer, but the individual overall survival probability is still difficult to estimate. Purpose To develop a prognostic risk score using PSMA PET-derived organ-specific total tumor volumes for predicting overall survival in patients with prostate cancer. Materials and Methods Men with prostate cancer who underwent PSMA PET/CT from January 2014 to December 2018 were evaluated retrospectively. All patients from center A were split into training (80%) and internal validation (20%) cohorts. Randomly selected patients from center B were used for external validation. Organ-specific tumor volumes were automatically quantified from PSMA PET scans by a neural network. A prognostic score was selected using multivariable Cox regression guided by the Akaike information criterion (AIC). The final prognostic risk score fitted on the training set was applied to both validation cohorts. Results A total of 1348 men (mean age, 70 years ± 8 [SD]) were included, with 918 patients in the training cohort, 230 in the internal validation cohort, and 200 in the external validation cohort. The median follow-up time was 55.7 months (IQR, 46.7-65.1 months; >4 years; 429 deaths occurred). A body weight-adjusted prognostic risk score integrating total, bone, and visceral tumor volumes obtained high C index values in the internal (0.82) and external (0.74) validation cohorts, as well as in patients with castration-resistant (0.75) and hormone-sensitive (0.68) disease. The fit of the statistical model for the prognostic score was improved compared with a model containing total tumor volume only (AIC, 3324 vs 3351; likelihood ratio test, P < .001). Calibration plots ascertained good model fit. Conclusion The newly developed risk score that included prostate-specific membrane antigen PET-derived organ-specific tumor volumes had good model fit for predicting overall survival in both internal and external validation cohorts. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Civelek in this issue.

Summating Potential as Marker of Intracochlear Position in Bipolar Electrocochleography.

OBJECTIVES: Cochlear implantation criteria include subjects with residual low-frequency hearing. To minimize implantation trauma and to avoid unwanted interactions of electric- and acoustic stimuli, it is often recommended to stop cochlear implantation before the cochlear implant (CI) reaches the cochlear partition with residual hearing, as determined by an audiogram. For this purpose, the implant can be used to record acoustically evoked signals during implantation, including cochlear compound action potentials (CAP), cochlear microphonics (CMs), and summating potentials (SPs). The former two have previously been used to monitor residual hearing in clinical settings. DESIGN: In the present study we investigated the use of intracochlear, bipolar SP recordings to determine the exact cochlear position of the contacts of implanted CIs in guinea pig cochleae (n = 13). Polarity reversals of SPs were used as a functional marker of intracochlear position. Micro computed tomography (µCT) imaging and a modified Greenwood function were used to determine the cochleotopic positions of the contacts in the cochlea. These anatomical reconstructions were used to validate the SP-based position estimates. RESULTS: The precision of the SP-based position estimation was on average within ± 0.37 octaves and was not impaired by moderate hearing loss caused by noise exposure after implantation. It is important to note that acute hearing impairment did not reduce the precision of the method. The cochleotopic position of CI accounted for ~70% of the variability of SP polarity reversals. Outliers in the dataset were associated with lateral CI positions. Last, we propose a simplified method to avoid implantation in functioning parts of the cochlea by approaching a predefined frequency region using bipolar SP recordings through a CI. CONCLUSIONS: Bipolar SP recordings provide reliable information on electrode position in the cochlea. The position estimate remains reliable after moderate hearing loss. The technique presented here could be applied during CI surgery to monitor the CI approach to a predefined frequency region.

Intravenous Midazolam as More Effective Than Propofol for Preventing Pruritus After Intrathecal Sufentanil in Surgical Patients: A Randomized Blinded Trial.

BACKGROUND: Pruritus is a troublesome side effect of intrathecal opioids. Midazolam can reinforce GABA-mediated inhibition of the medullary dorsal horn neurons, and thus theoretically has potential to suppress opioid-induced pruritus. OBJECTIVES: This prospective double-blinded randomized trial aimed at comparing the effects of propofol, midazolam, and a combination of the two on the prevention of pruritus induced by intrathecal sufentanil. METHODS: Eighty-four patients undergoing spinal anesthesia with 3 mL hyperbaric bupivacaine 0.5% and 5 µg sufentanil (1 mL) were randomly allocated to one of the three study groups: Group 1, who were administered 20 mg intravenous (IV) propofol bolus, then 50 µg/kg/min IV infusion; Group 2, who were administered 0.03 mg/kg IV midazolam bolus, then 0.02 mg/kg/h IV infusion; and Group 3, who were administered 10 mg IV propofol and 0.015 mg/kg IV midazolam bolus, then 25 µg/kg/min propofol and 0.01 mg/kg/h midazolam IV infusion. The incidence rates and severity of pruritus were assessed intraoperatively and postoperatively for 24 hours. RESULTS: The Ramsay Sedation Score was highest for the propofol group throughout the duration of the anesthetic process. Overall, 17 patients in the propofol group (60.7%), eight patients in the midazolam group (28.6%), and nine patients in the propofol-midazolam group (32.1%) developed pruritus (P = 0.027). Intraoperative pruritus was observed in seven patients in the propofol group (25%), two patients in the midazolam group (7.1%), and five patients in the midazolam-propofol group (17.9%) (P = 0.196). Postoperative pruritus developed in 12 patients in the propofol group (42.9%), six patients in the midazolam group (21.4%), and four patients in the midazolam-propofol group (14.3%) (P = 0.041). There was no significant difference between the groups with respect to the severity of pruritus (P > 0.05). CONCLUSIONS: This study showed that in comparison with propofol, the administration of 0.03 mg/kg IV midazolam bolus followed by 0.02 mg/kg/h could be more effective in the prevention of intrathecal sufentanil-induced pruritus without increasing sedation and other side effects.

Does Ramadan Fasting Adversely Affect Cognitive Function in Young Females?

We examined the effects of Ramadan fasting on cognitive function in 17 female athletes. Data were obtained from participants of two fasting (n = 9) and nonfasting (n = 8) groups at three periods of the study (before Ramadan, at the third week in Ramadan, and after Ramadan). Digit span test (DST) and Stroop color test were employed to assess short-term memory and inhibition/cognitive flexibility at each time point. There were no significant changes for DST and Stroop task 1 in both groups, whereas Stroop task 2 and task 3 showed significant improvements in Ramadan condition (p < 0.05). Interference indices did not change significantly across the study except in post-Ramadan period of fasting group (p < 0.05). Group × week interaction was significant only for error numbers (p < 0.05). Athletes in nonfasting showed a significant decrease in number of errors in Ramadan compared to baseline (p < 0.05). The results suggest that Ramadan fasting may not adversely affect cognitive function in female athletes.