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Background The low organ donation rate in Germany is associated with deficiencies in the identification of patients at risk of developing brain death. An automated digital clinical support system (DETECT) was designed to prospectively identify intensive care patients who are at risk of developing brain death. The objective of the study is to evaluate the effectiveness of DETECT in the detection of patients with severe brain injury who progress toward brain death compared to standard practice without DETECT. Methods The study will follow a multicentre, cluster-randomized, controlled design conducted at 19 sites in Germany over a 30-month period. The study will include patients aged ≥ 18 years with primary or secondary acute brain injury, requiring mechanical ventilation and death during hospital stay. DETECT periodically processes real-time data from the ICU information system to screen for a combination of coma and absent bilateral pupillary light reflexes—both considered early indicators of impending brain death. In the event of a positive screen, an automated notification will be sent to the designated transplant coordinators. The email is intended to prompt clinical assessment of the detected patient and, if necessary, initiate a guideline-based brain death evaluation. The primary endpoint is the identification of patients who develop brain death during hospitalization. Secondary endpoints encompass missed identification of potential brain death cases and deceased organ donations. Upon completion of the study, a survey will be conducted to investigate the stakeholders’ experiences with DETECT. Discussion Findings will provide insights into the effectiveness of an automated digital support system for the detection of patients at risk of developing brain death and potential organ donors. Automation may enhance ICU workflow efficiency and timely decision-making in organ donation processes. Trial registration ClinicalTrials.gov NCT06293170. Registered on March 5, 2024

Objectives To develop and test zone-specific prostate-specific antigen density (sPSAD) combined with PI-RADS to guide prostate biopsy decision strategies (BDS). Methods This retrospective study included consecutive patients, who underwent prostate MRI and biopsy (01/2012–10/2018). The whole gland and transition zone (TZ) were segmented at MRI using a retrained deep learning system (DLS; nnU-Net) to calculate PSAD and sPSAD, respectively. Additionally, sPSAD and PI-RADS were combined in a BDS, and diagnostic performances to detect Grade Group ≥ 2 (GG ≥ 2) prostate cancer were compared. Patient-based cancer detection using sPSAD was assessed by bootstrapping with 1000 repetitions and reported as area under the curve (AUC). Clinical utility of the BDS was tested in the hold-out test set using decision curve analysis. Statistics included nonparametric DeLong test for AUCs and Fisher-Yates test for remaining performance metrics. Results A total of 1604 patients aged 67 (interquartile range, 61–73) with 48% GG ≥ 2 prevalence (774/1604) were evaluated. By employing DLS-based prostate and TZ volumes (DICE coefficients of 0.89 (95% confidence interval, 0.80–0.97) and 0.84 (0.70–0.99)), GG ≥ 2 detection using PSAD was inferior to sPSAD (AUC, 0.71 (0.68–0.74)/0.73 (0.70–0.76); p < 0.001). Combining PI-RADS with sPSAD, GG ≥ 2 detection specificity doubled from 18% (10–20%) to 43% (30–44%; p < 0.001) with similar sensitivity (93% (89–96%)/97% (94–99%); p = 0.052), when biopsies were taken in PI-RADS 4-5 and 3 only if sPSAD was ≥ 0.42 ng/mL/cc as compared to all PI-RADS 3-5 cases. Additionally, using the sPSAD-based BDS, false positives were reduced by 25% (123 (104–142)/165 (146–185); p < 0.001). Conclusion Using sPSAD to guide biopsy decisions in PI-RADS 3 lesions can reduce false positives at MRI while maintaining high sensitivity for GG ≥ 2 cancers. Clinical relevance statement Transition zone-specific prostate-specific antigen density can improve the accuracy of prostate cancer detection compared to MRI assessments alone, by lowering false-positive cases without significantly missing men with ISUP GG ≥ 2 cancers. Key Points • Prostate biopsy decision strategies using PI-RADS at MRI are limited by a substantial proportion of false positives, not yielding grade group ≥ 2 prostate cancer. • PI-RADS combined with transition zone (TZ)-specific prostate-specific antigen density (PSAD) decreased the number of unproductive biopsies by 25% compared to PI-RADS only. • TZ-specific PSAD also improved the specificity of MRI-directed biopsies by 9% compared to the whole gland PSAD, while showing identical sensitivity.

Purpose To evaluate the performance of real-time MRI/ultrasound (MRI/US) fusion-guided targeted biopsy (TB) in men with primary and repeat biopsies and correlate the prostate cancer detection rate (CDR) with the PI-RADS score. Methods Analysis included 408 consecutive men with primary and prior negative biopsies who underwent TB and 10-core random biopsy (RB) between January 2012 and January 2015. TB was performed with a real-time MRI/US fusion platform with sensor-based registration. Clinically significant PCa was defined as Gleason score (GS) ≥7 or GS 6 with maximal cancer core length ≥4 mm for TB and according to Epstein criteria for RB. Results The overall CDR was 56 % (227/408). The CDR for primary biopsy was 74 % (60/81) and 57 % (67/117), 49 % (62/126), 45 % (38/84) for patients with 1, 2 and ≥3 prior negative biopsies. CDRs correlated with PI-RADS 2/3/4/5 were 16 % (5/32), 26 % (29/113), 62 % (94/152) and 89 % (99/111), respectively. The rates of significant tumors in relation to PI-RADS 2/3/4/5 were 60 % (3/5), 66 % (19/29), 74 % (70/94), 95 % (94/99). In 139 (61 %) cases with radical prostatectomy (RP), the rates of ≥pT3 tumors in correlation with PI-RADS 4 and 5 were 20 % (11/56) and 49 % (32/65). PI-RADS constituted the strongest predictor of significant PCa detection ( p  < 0.007). Conclusions Real-time MRI/US fusion-guided TB combined with RB improved PCa detection in patients with primary and repeat biopsies. The CDR was strongly correlated with a rising PI-RADS score, values of 4 and 5 increasing the detection of clinically significant tumors and leading to a higher histological stage after RP.

Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

Background Unlike other domestic mammals, in which metaphase-II oocytes are ovulated, canine ovulation is characterized by the release of primary oocytes, which may take 12 to up to 36 hours. Further 60 hours are needed for maturation to secondary oocytes which then remain fertile for about 48 hours. Oestrus takes 7 to 10 days on average and may start as early as a week before ovulation. This together with the prolonged process of post-ovulatory oocyte maturation requires an according longevity of spermatozoa in the female genital tract in order to provide a population of fertile sperm when oocytes have matured to fertilizability. Therefore the distribution and viability of spermatozoa in the bitch genital tract was examined during post-ovulatory oocyte maturation. Methods Thirteen beagle bitches were inseminated on the day of sonographically verified ovulation with pooled semen of two beagle dogs containing one billion progressively motile spermatozoa. Ovariohysterectomy was performed two days later (group 1, n = 6) and four days later (group 2, n = 7). The oviduct and uterine horn of one side were flushed separately and the flushing’s were checked for the presence of gametes. The oviducts including the utero-tubal junction and the uterine horns, both the flushed and unflushed, were histologically examined for sperm distribution. Results The total number of spermatozoa recovered by flushing was low and evaluation of viability was limited. Prophase-I oocytes were collected from oviduct flushing in group 1, whereas unfertilized metaphase-II oocytes were detected in group 2. From day 2 to day 4 after ovulation a significant decrease in the percentage of glands containing sperm (P<0.05) and a marked reduction of the mean sperm number in uterine horn glands were observed. A concomitant diminution of spermatozoa was indicated in the utero-tubal junction accompanied by a slight increase in sperm numbers in the mid oviduct. Conclusions Oocyte maturation to metaphase-II stage is accompanied by a continuous sperm detachment and elimination in the uterine horns. Entrance of spermatozoa into the caudal oviduct seems to be steadily controlled by the utero-tubal junction thus providing a selected sperm population to be shifted towards the site of fertilization when oocyte maturation is completed.

Canine distemper virus (CDV) exhibits a profound lymphotropism that causes immunosuppression and increased susceptibility of affected dogs to opportunistic infections. Similar to human measles virus, CDV is supposed to inhibit terminal differentiation of dendritic cells (DCs), responsible for disturbed repopulation of lymphoid tissues and diminished antigen presenting function in dogs. In order to testify the hypothesis that CDV-infection leads to an impairment of professional antigen presenting cells, canine DCs have been generated from peripheral blood monocytes in vitro and infected with CDV. Virus infection was confirmed and quantified by transmission electron microscopy, CDV-specific immunofluorescence, and virus titration. Flow cytometric analyses revealed a significant down-regulation of the major histocompatibility complex class II and co-stimulatory molecules CD80 and CD86 in CDV-infected DCs, indicative of disturbed antigen presenting capacity. Molecular analyses revealed an increased expression of the immune inhibitory cytokine interleukin-10 in DCs following infection. Results of the present study demonstrate that CDV causes phenotypical changes and altered cytokine expression of DCs, which represent potential mechanisms to evade host immune responses and might contribute to immune dysfunction and virus persistence in canine distemper.

Abstract URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs120232