[68Ga]Ga-FAPI-46 PET/CT for penile cancer - a feasibility study.

PURPOSE: Penile cancer is a rare entity and has a good prognosis in localized stage. Delayed surgical treatment of lymphatic disease is associated with poor overall survival but conventional imaging cannot detect occult lymph node metastasis sufficiently. Imaging cancer related fibroblasts has shown promising results as non-invasive staging tool in various tumor entities but has not yet been evaluated in penile cancer. METHODS: In this single-center pilot study, patients planned for surgical treatment for penile cancer underwent preoperatively [68Ga]Ga-FAPI-46 PET/CT. Post-operative histopathology was compared to [68Ga]Ga-FAPI-46 PET/CT results. RESULTS: From January 2022 to June 2022, a total number 11 patients with histopathologically proven penile cancer underwent surgery and received [68Ga]Ga-FAPI-46 PET/CT prior therapy. 8 primary tumor sites and 4 lymph node regions were analyzed. FAPI uptake was increased on primary tumor site (SUVmax 16.2 (9.1 - 25.8)). Histopathological proven lymph node regions showed highly increased FAPI uptakes (SUVmax 17.9 (16.4 - 23.5) on [68Ga]Ga-FAPI-46 PET/CT. CONCLUSION: In this first pilot cohort, there were no false-positive FAPI uptake which might allow the detection of occult lymph node metastasis by [68Ga]Ga-FAPI-46 PET/CT and might consequently lead to omitting lymph node regions during surgery that had no increased FAPI uptake pre-operatively.

Trends and outcomes of hospitalized patients with priapism in Germany: results from the GRAND study.

We aimed to provide evidence on the trends and in-hospital outcomes of patients with low- and high-flow priapism through the largest study in the field. We used the GeRmAn Nationwide inpatient Data (GRAND), provided by the Research Data Center of the Federal Bureau of Statistics (2008-2021), and performed multiple patient-level analyses. We included 6,588 men with low-flow and 729 with high-flow priapism. Among patients with low-flow priapism, 156 (2.4%) suffered from sickle cell disease, and 1,477 (22.4%) patients required shunt surgery. Of them, only 37 (2.5%) received a concomitant penile prosthesis implantation (30 inflatable and 7 semi-rigid prosthesis). In Germany, the total number of patients with low-flow priapism requiring hospital stay has steadily increased, while the number of patients with high-flow priapism requiring hospital stay has decreased in the last years. Among patients with high-flow priapism, 136 (18.7%) required selective artery embolization. In men with low-flow priapism, sickle cell disease was associated with high rates of exchange transfusion (OR: 21, 95% CI: 14-31, p < 0.001). The length of hospital stay (p = 0.06) and the intensive care unit admissions (p = 0.9) did not differ between patients with low-flow priapism due to sickle cell disease versus other causes of low-flow priapism. Accordingly, in men with high-flow priapism, embolization was not associated with worse outcomes in terms of length of hospital stay (p > 0.9), transfusion (p = 0.8), and intensive care unit admission (p = 0.5). Low-flow priapism is an absolute emergency that requires shunt surgery in more than one-fifth of all patients requiring hospital stay. On the contrary, high-flow priapism is still managed, in most cases, conservatively.

Genetic background and thermal regime influence adaptation to novel environment in the seed beetle, Callosobruchus maculatus.

Climate change is associated with the increase in both the mean and variability of thermal conditions. Therefore, the use of more realistic fluctuating thermal regimes is the most appropriate laboratory method for predicting population responses to thermal heterogeneity. However, the long- and short-term implications of evolving under such conditions are not well understood. Here, we examined differences in key life-history traits among populations of seed beetles (Callosobruchus maculatus) that evolved under either constant control conditions or in an environment with fluctuating daily temperatures. Specifically, individuals from two distinct genetic backgrounds were kept for 19 generations at one of two temperatures, a constant temperature (T = 29 °C) or a fluctuating daily cycle (Tmean = 33 °C, Tmax = 40 °C, and Tmin = 26 °C), and were assayed either in their evolved environment or in the other environment. We found that beetles that evolved in fluctuating environments but were then switched to constant 29 °C conditions had far greater lifetime reproductive success compared with beetles that were kept in their evolved environments. This increase in reproductive success suggests that beetles raised in fluctuating environments may have evolved greater thermal breadth than control condition beetles. In addition, the degree of sexual dimorphism in body size and development varied as a function of genetic background, evolved thermal environment, and current temperature conditions. These results not only highlight the value of incorporating diel fluctuations into climate research but also suggest that populations that experience variability in temperature may be better able to respond to both short- and long-term changes in environmental conditions.

mpMRI-targeted biopsy of the prostate in men ≥ 75 years. 7-year report from a high-volume referral center.

OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) -Ultrasound- fusion guided biopsy of the prostate (FBx) is the new gold standard for the detection of prostate cancer. Hallmark studies showing superior detection rates of FBx over randomized biopsies routinely excluded patients≥75 years and information on outcome of FBx on this patient cohort is sparse. As a large referral center, we have performed FBx on a substantial number of patients this age. By evaluating outcome of FBx of patients over the age of 75 years we wanted to close the gap of knowledge on this patient cohort. MATERIALS AND METHODS: Between 2015 -2022, 1577 patients underwent FBx at our department and were considered for analysis. Clinical and histopathological parameters were recorded. Clinical data comprised age at FBx, serum level of Prostate-specific antigen (PSA), prostate volume, PSA-density, history of previous biopsies of the prostate, result of the digital rectal examination (DRE) and assessment of the indexlesion of mpMRI according to the Prostate Imaging and Reporting Data System (PI-RADS). Univariate analysis and multivariable logistic regression was used to identify age barrier of 75 years as a potential risk factor of detection of clinically significant prostate cancer by FBx. RESULTS: 379/1577 patients (24%) were≥75 years and 1198/1577 (76%) patients were < 75 years, respectively. Preoperative PSA was significantly higher in patients≥75 years compared to patients < 75 years (9.54 vs. 7.8, p < 0.001). Patients≥75 years presented significantly more often with mpMRI target lesions classified as PI-RADS 5 compared to patients < 75 years (45% vs. 29%, p < 0.001). Detection rate of clinically significant prostate cancer was significantly higher in patients≥75 years compared to patients < 75 years (63% vs. 43%, p < 0.001). Aggressive prostate cancer grade ISUP 5 was significantly more often detected in patients≥75 years compared to patients < 75 years (13% vs. 8%, p = 0.03). On multivariable logistic regression model adjusted for PSA and PI-RADS score, age barrier of 75 years was identified as a significant risk factor for the detection of clinically significant prostate cancer by FBx (OR: 1.77, 95% CI: 1.36 -2.31, p < 0.001). CONCLUSION: After evaluation of a large patient cohort, we show that age≥75 years represents a significant risk factor for the detection of clinically significant prostate cancer. Further studies on mid- and long term outcome are necessary to draw conclusions for clinical decision making in this patient cohort.

Added value of randomised biopsy to multiparametric magnetic resonance imaging-targeted biopsy of the prostate in a contemporary cohort.

OBJECTIVE: To assess the added value of concurrent systematic randomised ultrasonography-guided biopsy (SBx) to multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and the additional rate of overdiagnosis of clinically insignificant prostate cancer (ciPCa) by SBx in a large contemporary, real-world cohort. PATIENTS AND METHODS: A total of 1552 patients with positive mpMRI and consecutive mpMRI-targeted biopsy and SBx were enrolled. Added value and the rate of overdiagnosis by SBx was evaluated. PRIMARY OUTCOME: added value of SBx, defined as detection rate of clinically significant PCa (csPCa; International Society of Urological Pathology [ISUP] Grade ≥2) by SBx, while mpMRI-targeted biopsy was negative or showed ciPCa (ISUP Grade 1). SECONDARY OUTCOME: rate of overdiagnosis by SBx, defined as detection of ciPCa in patients with negative mpMRI-targeted biopsy and PSA level of <10 ng/mL. RESULTS: Detection rate of csPCa by mpMRI-targeted biopsy and/or SBx was 753/1552 (49%). Added value of SBx was 145/944 (15%). Rate of overdiagnosis by SBx was 146/656 (22%). Added value of SBx did not change when comparing patients with previous prostate biopsy and biopsy naïve patients. In multivariable analysis, a Prostate Imaging-Reporting and Data System (PI-RADS) 4 index lesion (odds ratio [OR] 3.19, 95% confidence interval [CI] 1.66-6.78; P = 0.001), a PI-RADS 5 index lesion (OR 2.89, 95% CI 1.39-6.46; P = 0.006) and age (OR 1.05, 95% CI 1.03-1.08; P < 0.001) were independently associated with added value of SBx. CONCLUSIONS: In our real-world analysis, we saw a significant impact on added value and added rate of overdiagnosis by SBx. Subgroup analysis showed no significant decrease of added value in any evaluated risk group. Therefore, we do not endorse omitting concurrent SBx to mpMRI-guided biopsy of the prostate.

Perioperative outcomes of penile prosthesis implantation in Germany: results from the GRAND study.

We aimed to assess the recommended annual hospital volume for inflatable penile prosthesis implantation (PPI) and to provide evidence on perioperative outcomes of semi-rigid and inflatable PPI in Germany. We used the GeRmAn Nationwide inpatient Data (GRAND) from 2005 to 2021 and report the largest study to date with 7,222 patients. 6,818 (94.4%) patients underwent inflatable and 404 (5.6%) semi-rigid PPI. Inflatable PPI was significantly associated with shorter length of hospital stay (difference of 2.2 days, 95%CI: 1.6-2.7, p < 0.001), lower odds of perioperative urinary tract infections (5.5% versus 9.2%; OR: 0.58, 95%CI: 0.41-0.84, p = 0.003) and surgical wound infections (1% versus 2.5%; OR: 0.42, 95%CI: 0.22-0.88, p = 0.012) compared to semi-rigid PPI. Overall, 4255 (62.4%) inflatable PPIs were undertaken in low- ( < 20 PPI/year) and 2563 (37.6%) in high-volume ( ≥ 20 PPI/year) centers. High-volume centers were significantly associated with shorter length of hospital stay (difference of 1.4 days, 95%CI: 1.2-1.7, p < 0.001) compared to low-volume centers. Our findings suggest that inflatable PPI leads to a shorter length of hospital stay and lower rates of perioperative urinary tract and surgical wound infections compared to semi-rigid PPI. Patients undergoing surgery in high-volume centers for inflatable PPI are discharged earlier from the hospital.

The Impact of Prostate Volume on the Prostate Imaging and Reporting Data System (PI-RADS) in a Real-World Setting.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a new cornerstone in the diagnostic pathway of prostate cancer. However, mpMRI is not devoid of factors influencing its detection rate of clinically significant prostate cancer (csPCa). Amongst others, prostate volume has been demonstrated to influence the detection rates of csPCa. Particularly, increasing volume has been linked to a reduced cancer detection rate. However, information about the linkage between PI-RADS, prostate volume and detection rate is relatively sparse. Therefore, the current study aims to assess the association between prostate volume, PI-RADS score and detection rate of csP-Ca, representing daily practice and contemporary mpMRI expertise. Thus, 1039 consecutive patients with 1151 PI-RADS targets, who underwent mpMRI-guided prostate biopsy at our tertiary referral center, were included. Prior mpMRI had been assessed by a plethora of 111 radiology offices, including academic centers and private practices. mpMRI was not secondarily reviewed in house before biopsy. mpMRI-targeted biopsy was performed by a small group of a total of ten urologists, who had performed at least 100 previous biopsies. Using ROC analysis, we defined cut-off values of prostate volume for each PI-RADS score, where the detection rate drops significantly. For PI-RADS 4 lesions, we found a volume > 61.5 ccm significantly reduced the cancer detection rate (OR 0.24; 95% CI 0.16-0.38; p < 0.001). For PI-RADS 5 lesions, we found a volume > 51.5 ccm to significantly reduce the cancer detection rate (OR 0.39; 95% CI 0.25-0.62; p < 0.001). For PI-RADS 3 lesions, none of the evaluated clinical parameters had a significant impact on the detection rate of csPCa. In conclusion, we show that enlarged prostate volume represents a major limitation in the daily practice of mpMRI-targeted biopsy. This study is the first to define exact cut-off values of prostate volume to significantly impair the validity of PI-RADS assessed in a real-world setting. Therefore, the results of mpMRI-targeted biopsy should be interpreted carefully, especially in patients with prostate volumes above our defined thresholds.

Adverse Pathology after Radical Prostatectomy of Patients Eligible for Active Surveillance-A Summary 7 Years after Introducing mpMRI-Guided Biopsy in a Real-World Setting.

OBJECTIVE: Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx. SUBJECTS AND METHODS: Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA). RESULTS: A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx (p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS (p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx (p = 0.39). CONCLUSIONS: In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

Asymptomatic bacteriospermia and infertility-what is the connection?

OBJECTIVE: To determine the impact of asymptomatic bacteriospermia on semen quality in subfertile men. METHODS: We conducted a retrospective, single-centre cohort study in 1300 subfertile men. In those diagnosed with asymptomatic bacteriospermia we performed univariate and multivariate logistic regression models to evaluate the strain-specific association with semen parameters. RESULTS: Asymptomatic bacteriospermia was diagnosed in 3.2% of patients. The microbiological semen analysis revealed a poly-microbial result in 60%. The most common bacterial species were coagulase-negative Staphylococci species (71.4%), Streptococcus viridans (50.0%) and Enterococcus faecalis (26.2%). Sexually transmitted pathogens were identified in 11.9% of semen samples. The detection of Streptococcus viridians or Haemophilus parainfluenzae correlated with impaired sperm morphology (p < 0.05). The presence of coagulase-negative Staphylococci species or Enterococcus faecalis was associated with pathological low counts of live spermatozoa (p < 0.05). In multivariate analysis only Enterococcus faecalis showed a significant impact on sperm concentration (OR 4.48; 95% CI 1.06-22.10; p = 0.041). CONCLUSIONS: Asymptomatic bacteriospermia has always been a subject of great controversy. There is still an ongoing debate whether to treat or not to treat. Here, we demonstrate that asymptomatic bacteriospermia is clearly associated with impaired semen quality. Our findings speak in favour of strain-specific interactions with semen parameters. Especially Enterococcus faecalis seriously affects sperm concentration.

Pre-diagnosis urine exosomal RNA (ExoDx EPI score) is associated with post-prostatectomy pathology outcome.

PURPOSE: ExoDx Prostate IntelliScore (EPI) is a non-invasive urine exosome RNA-based test for risk assessment of high-grade prostate cancer. We evaluated the association of pre-biopsy test results with post-radical prostatectomy (RP) outcomes to understand the potential utility of EPI to inform invasive treatment vs active surveillance (AS) decisions. METHODS: Urine samples were collected from 2066 men scheduled for initial biopsy with PSA between 2 and 10 ng/mL, no history of prostate cancer, and ≥ 50 years across multiple clinical studies. 310 men proceeded to RP, of which 111 patients had Gleason group grade 1 (GG1) at biopsy and would have been potential candidates for AS. We compared pre-biopsy urine scores with ERSPC and PCPT multivariate risk calculator scores for men with GG1 at biopsy to post-RP pathology. RESULTS: Urine EPI scores were significantly lower in men with GG1 at biopsy than in men with > GG1 (p = 0.04), while there were no differences in multivariate risk scores used in standard clinical practice (p > 0.05). Further, EPI scores were significantly lower in men with GG1 at biopsy who remained GG1 post-RP compared to men upgraded to ≥ GG3 post-RP (p < 0.001). In contrast, none of the multiparametric risk calculators showed significant differences (p > 0.05). Men with GG1 at biopsy and EPI score < 15.6 had zero rate of upgrading to ≥ GG3 post-RP compared to 16.0% for EPI scores ≥ 15.6. CONCLUSIONS: The EPI urine biomarker outperformed the multivariate risk calculators in a homogenous risk group of pre-biopsy men. The EPI score was associated with low-risk pathology post-RP, with potential implications on informing AS decisions. TRIAL REGISTRATION: NCT02702856, NCT03031418, NCT03235687, NCT04720599.

Chronic Prostatitis/Chronic Pelvic Pain Syndrome Leads to Impaired Semen Parameters, Increased Sperm DNA Fragmentation and Unfavorable Changes of Sperm Protamine mRNA Ratio.

BACKGROUND: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters. METHODS: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers. RESULTS: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility. CONCLUSIONS: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.

Inbreeding reduces fitness of seed beetles under thermal stress.

Human-induced environmental change can influence populations both at the global level through climatic warming and at the local level through habitat fragmentation. As populations become more isolated, they can suffer from high levels of inbreeding, which contributes to a reduction in fitness, termed inbreeding depression. However, it is still unclear if this increase in homozygosity also results in a corresponding increase in sensitivity to stressful conditions, which could intensify the already detrimental effects of environmental warming. Here, in a fully factorial design, we assessed the life-long impact of increased inbreeding load and elevated temperature on key life history traits in the seed beetle, Callosobruchus maculatus. We found that beetles raised at higher temperatures had far reduced fitness and survival than beetles from control temperatures. Importantly, these negative effects were exacerbated in inbred beetles as a result of increased inbreeding load, with further detrimental effects manifesting on individual eclosion probability and lifetime reproductive success. These results reveal the harmful impact that increasing temperature and likelihood of habitat fragmentation due to anthropogenetic changes in environmental conditions could have on populations of organisms worldwide.

Kin but less than kind: within-group male relatedness does not increase female fitness in seed beetles.

Theory maintains within-group male relatedness can mediate sexual conflict by reducing male-male competition and collateral harm to females. We tested whether male relatedness can lessen female harm in the seed beetle Callosobruchus maculatus. Male relatedness did not influence female lifetime reproductive success or individual fitness across two different ecologically relevant scenarios of mating competition. However, male relatedness marginally improved female survival. Because male relatedness improved female survival in late life when C. maculatus females are no longer producing offspring, our results do not provide support for the role of within-group male relatedness in mediating sexual conflict. The fact that male relatedness improves the post-reproductive part of the female life cycle strongly suggests that the effect is non-adaptive. We discuss adaptive and non-adaptive mechanisms that could result in reduced female harm in this and previous studies, and suggest that cognitive error is a likely explanation.

Measurement of a Novel Biomarker, Secretory Phospholipase A2 Group IIA as a Marker of Sepsis: A Pilot Study.

INTRODUCTION: Early identification of sepsis is critical as early treatment improves outcomes. We sought to identify threshold values of secretory phospholipase A2 (sPLA2)-IIA that predict sepsis and bacterial infection compared to nonseptic controls in an emergency department (ED) population. MATERIALS AND METHODS: This is a prospective cohort of consenting adult patients who met two or more systemic inflammatory response syndrome (SIRS) criteria with clinical diagnosis of infectious source likely (septic patients). Controls were nonseptic consenting adults undergoing blood draw for other ED indications. Both groups had blood drawn, blind-coded, and sent to an outside laboratory for quantitative analysis of sPLA2-IIA levels. The study investigators reviewed patients' inpatient medical record for laboratory, imaging, and microbiology results, as well as clinical course. RESULTS: sPLA2-IIA levels were significantly lower in control patients as compared to septic patients (median = 0 ng/ml [interquartile range (IQR): 0-6.5] versus median = 123 ng/ml [IQR 44-507.75]; P < 0.0001). SPLA2-IIA levels were higher in patients with confirmed source (n = 28 patients, median = 186 ng/ml, 95% confidence interval = 115.1-516.8) as compared to those with no source identified or a viral source (n = 17, median = 68 ng/ml, 95% confidence interval = 38.1-122.7; P = 0.04). Using a cutoff value of 25 ng/ml, sPLA2-IIA had a sensitivity of 86.7% (confidence interval 72.5-94.5) and a specificity of 91.1% (confidence interval 77.9-97.1) in detecting sepsis. CONCLUSIONS: sPLA2-IIA shows potential as a biomarker distinguishing sepsis from other disease entities. Further study is warranted to identify predictive value of trends in sPLA-IIA during disease course in septic patients.