SARS-CoV-2 mRNA vaccination-induced immunological memory in human nonlymphoid and lymphoid tissues.

Tissue-resident lymphocytes provide organ-adapted protection against invading pathogens. Whereas their biology has been examined in great detail in various infection models, their generation and functionality in response to vaccination have not been comprehensively analyzed in humans. We therefore studied SARS-CoV-2 mRNA vaccine-specific T cells in surgery specimens of kidney, liver, lung, bone marrow, and spleen compared with paired blood samples from largely virus-naive individuals. As opposed to lymphoid tissues, nonlymphoid organs harbored significantly elevated frequencies of spike-specific CD4+ T cells compared with blood showing hallmarks of tissue residency and an expanded memory pool. Organ-derived CD4+ T cells further exhibited increased polyfunctionality over those detected in blood. Single-cell RNA-Seq together with T cell receptor repertoire analysis indicated that the clonotype rather than organ origin is a major determinant of transcriptomic state in vaccine-specific CD4+ T cells. In summary, our data demonstrate that SARS-CoV-2 vaccination entails acquisition of tissue memory and residency features in organs distant from the inoculation site, thereby contributing to our understanding of how local tissue protection might be accomplished.

[Quality of life and outcome after holmium laser enucleation of the prostate (HoLEP)]. / Lebensqualität und Outcome nach Holmiumlaserenukleation der Prostata (HoLEP).

BACKGROUND: Holmium Laser Enucleation of the Prostate (HoLEP) was established 20 years ago as an alternative to Transurethral Resection of the Prostate (TUR-P) based on improved morbidity in patients with benign prostate syndrome (BPS). HoLEP can be applied independently to almost all sizes of prostate glands and is recommended in national and international guidelines. Although the HoLEP procedure has a good reputation, many patients still prefer conservative treatment due to fears of side-effects such as pain and urinary incontinence. The aim of this study was to identify patients' feelings, fears and perception of their HoLEP treatment based on Patient-reported Outcome Measures (PROMs) via questionnaires. MATERIAL UND METHODS: During the time period from June to December 2020, 152 consecutive patients were treated by HoLEP due to BPS and were interviewed based on questionnaires right after their surgical treatment and 3 months later concerning their satisfaction as well as micturition and continence. Based on a written informed consent, 112 patients were included in the study, and a complete 3-month follow-up was available for 88 patients. RESULTS: The mean volume of enucleated prostate tissue was 62.1 [g] and the mean prostate volume estimated pre-operatively (trans-rectal ultrasound) was 83.1 [cm3]. Overall patient-reported satisfaction with the hospital stay including surgical treatment was 94.6%; after 3 months it was 91.8%. Concerning micturition, 76.5% of the patients reported satisfaction after surgery and 80.4% were satisfied after 3 months. Urinary incontinence was reported in 8.3% initially and in 9.1% after 3 months. Positive answers to questions concerning the quality of life index [L] were obtained in 62.1% initially and their number increased to 85.7% after 3 months. The share of negative answers decreased from 11.7% after surgery to 3.4% within the 3-month follow-up. DISCUSSION: HoLEP is a well-established treatment of BPS with lower side-effects compared with TUR-P according to the literature. To address doubts and misgivings, it is important to perform surveys on subjective patient satisfaction after the surgical procedure and over time. The high patient satisfaction could help future patients and the urologists treating them to establish the indication for HoLEP treatment earlier in order to avoid severe LUTS or catheterization.

Follow-up of men with a PI-RADS 4/5 lesion after negative MRI/Ultrasound fusion biopsy.

Magnetic resonance imaging/Ultrasound (MRI/US) fusion targeted biopsy (TB) in combination with a systematic biopsy (SB) improves cancer detection but limited data is available how to manage patients with a Prostate Imaging-Reporting and Data System (PI-RADS) ≥ 4 lesion and a negative biopsy. We evaluate the real-world management and the rate of clinically significant Prostate Cancer (csPCa) during follow-up. 1546 patients with a multi-parametric MRI (mpMRI) and a PI-RADS ≥ 3 who underwent SB and TB between January 2012 and May 2017 were retrospectively analyzed. 222 men with a PI-RADS ≥ 4 and a negative biopsy were included until 2019. For 177/222 (80%) complete follow-up data was obtained. 66/84 (78%) had an initial PI-RADS 4 and 18 (22%) a PI-RADS 5 lesion. 48% (84/177) received a repeat mpMRI; in the follow-up mpMRI, 39/84 (46%) lesions were downgraded to PI-RADS 2 and 11 (13%) to PI-RADS 3; three cases were upgraded and 28 lesions remained consistent. 18% (32/177) men underwent repeated TB and csPCa was detected in 44% (14/32). Our study presents real world data on the management of men with a negative TB biopsy. Men with a positive mpMRI and lesions with high suspicion (PI-RADS4/5) and a negative targeted biopsy should be critically reviewed and considered for repeat biopsy or strict surveillance. The optimal clinical risk assessment remains to be further evaluated.

Evolution of Targeted Prostate Biopsy by Adding Micro-Ultrasound to the Magnetic Resonance Imaging Pathway.

BACKGROUND: Although multiparametric magnetic resonance imaging (mpMRI) revolutionized the implementation of prostate biopsies, a considerable amount of clinically significant prostate cancer (csPCa) is missed when performing mpMRI-targeted biopsies only. Microultrasound (micro-US) is a new modality that allows real-time targeting of suspicious regions. OBJECTIVE: To evaluate micro-US of the prostate with real-time targeting of suspicious regions in patients suspected to have prostate cancer (PCa). DESIGN, SETTING, AND PARTICIPANTS: We examined 159 patients with prior mpMRI and suspicion of PCa with micro-US in the period from February to December 2018. Micro-US lesions were documented according to the prostate risk identification for micro-US (PRI-MUS) protocol, and were blinded to the mpMRI results and targeted independently of the mpMRI lesions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcomes were cancer detection rate, additional detection of csPCa, and International Society of Urological Pathology (ISUP) grade group upgrading via micro-US. RESULTS AND LIMITATIONS: PCa was found in 113/159 (71%) men, with 49% (78/159) having clinically significant cancer (csPCa; ISUP ≥ 2). Micro-US-targeted biopsies resulted in a higher ISUP grade group than the nontargeted biopsies in 26% (42/159), compared with both nontargeted and MRI-targeted biopsies in 16% (26/159). In 17% (27/159) of patients, targeted mpMRI-guided biopsy was negative with cancer identified in the micro-US-guided biopsy, of whom 20 had csPCa. The comparison with only MRI-positive patients is the main limitation of this analysis. CONCLUSIONS: Our data show an added benefit of micro-US in addition to mpMRI-targeted biopsies in a population of men at risk of PCa. A novel biopsy protocol with solely targeted biopsy with micro-US and mpMRI seems possible, replacing conventional ultrasound and omitting standard systematic biopsies. PATIENT SUMMARY: In this report, we looked at the performance of microultrasound in the setting of diagnosing prostate cancer. We found that microultrasound is a good addition to magnetic resonance imaging (MRI) of the prostate and presents an alternative for men who may not undergo MRI.

Validation of Prostate Imaging Reporting and Data System Version 2 for the Detection of Prostate Cancer.

PURPOSE: The second version of the PI-RADS™ (Prostate Imaging Reporting and Data System) was introduced in 2015 to standardize the interpretation and reporting of prostate multiparametric magnetic resonance imaging. Recently low cancer detection rates were reported for PI-RADS version 2 category 4 lesions. Therefore the aim of the study was to evaluate the cancer detection rate of PI-RADS version 2 in a large prospective cohort. MATERIALS AND METHODS: The study included 704 consecutive men with primary or prior negative biopsies who underwent magnetic resonance imaging/ultrasound fusion guided targeted biopsy and 10-core systematic prostate biopsy between September 2015 and May 2017. All lesions were rated according to PI-RADS version 2 and lesions with PI-RADS version 2 category 3 or greater were biopsied. An ISUP (International Society of Urological Pathology) score of 2 or greater (ie Gleason 3 + 4 or greater) was defined as clinically significant prostate cancer. RESULTS: The overall cancer detection rate of PI-RADS version 2 categories 3, 4 and 5 was 39%, 72% and 91% for all prostate cancer, and 23%, 49% and 77% for all clinically significant prostate cancer, respectively. If only targeted biopsy had been performed, 59 clinically significant tumors (16%) would have been missed. The PI-RADS version 2 score was significantly associated with the presence of prostate cancer (p <0.001), the presence of clinically significant prostate cancer (p <0.001) and the ISUP grade (p <0.001). CONCLUSIONS: PI-RADS version 2 is significantly associated with the presence of clinically significant prostate cancer. The cancer detection rate of PI-RADS version 2 category 4 lesions was considerably higher than previously reported. When performing targeted biopsy, the combination with systematic biopsy still provides the highest detection of clinically significant prostate cancer.

Primary magnetic resonance imaging/ultrasonography fusion-guided biopsy of the prostate.

OBJECTIVE: To examine the performance of a primary magnetic resonance imaging (MRI)/ultrasonography (US) fusion-guided targeted biopsy (TB), and in combination with an added systematic biopsy (SB). PATIENTS AND METHODS: Analysis of 318 consecutive biopsy-naïve men with suspicious multiparametric MRI (mpMRI; Prostate Imaging Reporting and Data System [PI-RADS] score ≥3) undergoing transrectal TB and 10-core SB between January 2012 and December 2016. The indication for performing mpMRI was based on clinical parameters and decided by the treating urologist before admission. TB was performed with a sensor-based MRI/US fusion-guided platform. Clinically significant prostate cancer was defined as Gleason score ≥4 + 3 = 7 (International Society of Urological Pathology Grade [ISUP] grade 3) or maximum cancer core length of ≥6 mm. RESULTS: A median (interquartile range) of 14 (13-14) biopsies per case were taken. The overall cancer detection rate (CDR) was 77% (245/318). The TB alone detected 67% of prostate cancers and the SB alone detected 70%. The PI-RADS dependent CDR for the combination of TB/SB were 38% (21/55), 78% (120/154) and 95% (104/109) for PI-RADS scores of 3/4/5, respectively. Clinically significant prostate cancer was diagnosed by the combination of TB and SB in 195 men (61%) and by TB alone in 163 cases (51%). The number of missed or underestimated prostate cancers with a Gleason score ≥8 for TB alone was 31 (10%, P < 0.001) and 21 (7%, P < 0.001) for SB alone in comparison with the results of the combination of TB and SB. The rate of insignificant prostate cancer was comparable for the combination of TB and SB and TB alone (50/318, 16% vs 50/318, 16%). CONCLUSIONS: Pre-biopsy mpMRI is of incremental value in increasing the detection of clinically significant prostate cancer in biopsy-naïve patients with suspicion of prostate cancer. Combining TB with SB further improved the diagnostic accuracy without increasing the rate of insignificant prostate cancer.