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The modern tontine : an innovative instrument for longevity risk management in an aging society
(2020)
We investigate whether a historical pension concept, the tontine, yields enough innovative potential to extend and improve the prevailing privately funded pension solutions in a modern way. The tontine basically generates an age-increasing cash flow, which can help to match the increasing financing needs at old ages. In contrast to traditional pension products, however, the tontine generates volatile cash flows, which means that the insurance character of the tontine cannot be guaranteed in every situation. By employing Multi Cumulative Prospect Theory (MCPT) we answer the question to what extent tontines can be a complement to or a substitute for traditional annuities. We find that it is only optimal to invest in tontines for a certain range of initial wealth. In addition, we investigate in how far the tontine size, the volatility of individual liquidity needs and expected mortality rates contribute to the demand for tontines.
In optogenetischen Anwendungen, welche die Manipulation von zellulären Aktivitäten durch Licht ermöglichen, werden die Eigenschaften von mikrobiellen Rhodopsinen, einer Familie natürlich vorkommender lichtgesteuerter Proteine, ausgenutzt.
In der vorliegenden Arbeit wurden die einwärts transportierende Protonenpumpe NsXeR, sowie die auswärts Natriumionenpumpe KR2 untersucht. Des Weiteren wurden Tandem Proteine betrachtet, die mikrobielle Rhodopsine kombinieren mit dem Chemokinrezeptor CXCR4, der durch SDF1 aktiviert und anschließend in Endosomen internalisiert wird.
Für die Untersuchung des Mechanismus, der die Vektorialität in NsXeR bestimmt, wurde eine umfassende elektrophysiologische Studie durchgeführt. In Patch Clamp Messungen an NsXeR exprimierenden NG108-15 Zellen wurden bei kontinuierlicher 561 nm Beleuchtung aktive Einwärtsströme entgegen eines elektrochemischen Gradienten gemessen. Ein Einfluss des intrazellulären pHs auf die steady-state Ströme und deren Abfallkinetik konnte nicht festgestellt werden. Der Vergleich der exponentiellen Abfallrate k2 mit den Übergängen im NsXeR Photozyklus, lässt den Schluss zu, dass der ratenlimitierende Schritt der MII Zerfall ist.
Die elektrogenen Schritte im NsXeR Photozyklus wurden mit elektrischen Messungen an der black lipid membrane (BLM) an NsXeR Proteoliposomen bestimmt. Die Belichtung mit 20 ns Lichtpulsen bei 556 nm rufen Spannungssignale hervor, die exponentiell gefittet wurden, wobei drei elektrogene Schritte identifiziert werden konnten. Bei pH 7.4 betrugen die ermittelten Zeitkonstanten etwa 220 µs, 1 ms und 15 ms, denen 42%, 10% und 48% an der Gesamtladungsverschiebung zugeordnet wurden. Die elektrogenen Schritte konnten den Übergängen im Photozyklus zugeordnet werden, wobei der erste Schritt mit t1 dem MI Aufbau (Deprotonierung Schiff’sche Base, Protonenabgabe zur intrazellulären Seite) zugeschrieben wurde. t2 wurde dem MI→MII Übergang (Switch, Zugänglichkeitsänderung vom Intra- zum Extrazellulären) zugeordnet und t3 korreliert mit dem MII Zerfall (Reprotonierung Schiff’sche Base, Protonenaufnahme von der extrazellulären Seite).
Die Kinetik und der Ladungstransportanteil des zweiten elektrogenen Schritts haben keine starke pH Abhängigkeit, was sich dadurch erklären lässt, dass t2 durch eine Konformationsänderung bestimmt wird. t1 und t3 werden bei höheren pH Werten beschleunigt, was sich bei t1 mit einer erleichterten intrazellulären Protonenabgabe erklären lässt. Für t3 wurde eine Reprotonierung durch eine Donor Gruppe Asp76 vorgeschlagen. Die pH-sensitive Änderung der relativen Ladungstransferanteile des ersten und dritten elektrogenen Schrittes (∆ΨI und ∆ΨIII) wurden durch eine mögliche Verzögerung der frühen Protonenabgabe bei niedrigen pH Werten erklärt.
Der mutmaßliche Protonenakzeptor Asp220 wurde gegen Asn und Glu ausgetauscht und in Patch Clamp sowie UV-Vis Spektroskopie Messungen untersucht. Für D220N wurden keine Pumpströme und kein Einfluss auf die maximale Absorptionswellenlänge λmax festgestellt. D220E dagegen führte zu einer Erniedrigung des pKa-Werts der Schiff’schen Base und zu einer Verminderung der Iss-Abfallsrate k2 in Patch Clamp Dauerbelichtungsmessungen (D220E k2 = 27.1 ± 1.8 Hz, Wildtyp k2 = 83.1 ± 2.6 Hz). Daraus konnte geschlossen werden, dass Asp220 wesentlich für den Protonentransport ist und nicht als Gegenion für die protonierte Schiff’sche Base dient.
In Patch Clamp Experimenten bei 561 nm Dauerbelichtung und zusätzlicher gepulster Belichtung bei 355 nm wurde der Blaulichteffekt an NsXeR untersucht, bei dem Proteine im M Intermediat ein Photon absorbieren und unter Reprotonierung der Schiff’schen Base in den Grundzustand zurückkehren.
Für NsXeR konnte eine Potentialabhängigkeit für die Richtung der transienten Ströme, die durch die
355 nm Belichtung hervorgerufen wurden, festgestellt werden. Beim NsXeR Blaulichteffekt scheint eine
Reprotonierung der Schiff’schen Base von beiden Seiten möglich zu sein, was auf die unterschiedlichen Zugänglichkeiten in den beiden M Zuständen MI und MII zurückgeführt wurde. Es wurde ein Modell vorgeschlagen, welches auf einem potentialabhängigen Gleichgewicht zwischen MI und MII basiert.
In Patch Clamp Messungen an KR2 exprimierenden NG108-15 Zellen wurden die Pumpströme untersucht, die durch den auswärts Transport von Na+ und H+ hervorgerufen wurden. Die Na+-Konzentrationen der intra- und extrazellulären Lösungen wurden symmetrisch variiert und die steady-state Ströme Iss bei 532 nm Dauerbelichtung betrachtet. Mit steigender Na+-Konzentration zeigte sich ein Übergang von einer linearen Potentialabhängigkeit der Iss, zu einem sättigungsähnlichen Verhalten bis hin zu einer fast glockenförmigen Form. Da die exponentielle Abfallrate der steady-state Ströme k2 in ihrer Potentialabhängigkeit mit den Iss korrelierte, konnte geschlossen werden, dass die Ströme überwiegend kinetisch limitiert sind. Die Erhöhung der Rate k2 mit steigender Na+-Konzentration zwischen -120 mV und -60 mV deutet darauf hin, dass die Na+-Aufnahme von der intrazellulären Seite bei diesen Bedingungen die Limitierung für die Pumpe darstellt.
Unter Na+-“freien” Bedingungen wurde der Einfluss des intrazellulären pHs untersucht. Für die Rate k2 wurde eine Erhöhung bei niedrigen pH Werten festgestellt und die Potentiale E0 (Iss = 0 pA) verschoben bei niedrigem intrazellulärem pH zu hyperpolarisierenden Potentialen. Daraus lässt sich schließen, dass die steady-state Ströme durch den Transport von Protonen hervorgerufen wurden.
In Messungen mit gepulster 530 nm Belichtung wurden die transienten Pumpströme gemessen und durch exponentielles Fitten des Stromabfalls drei elektrogene Schritte identifiziert. Eine Abhängigkeit vom Potential und der Na+-Konzentration konnte nur für den dritten Schritt mit der Rate 1/τ3 festgestellt werden, wobei 1/τ3 mit der Na+-Konzentration und bei positiveren Potentialen steigt. Unter Na+-“freien” Bedingungen steigt 1/τ3 auch mit niedrigeren intrazellulären pH Werten. Die elektrogenen Schritte wurden dem KR2 Photozyklus zugeordnet, wobei ein Modell angewendet wurde, das einen M1→M2 Übergang einführt. Diesem wurde der zweite elektrogene Schritt zugeordnet. Die relativen Ladungstransportanteile Q2 und Q3 des zweiten und dritten elektrogenen Schrittes sind sowohl potential- als auch Na+-abhängig. Um dieses Verhalten zu erklären, wurde ein Modell vorgeschlagen, bei dem ein Ausgleichsladungstransfer in Form von einer Protonenabgabe und -wiederaufnahme während des Photozyklus eingeführt wurde.
In Patch Clamp Messungen wurde die erhaltene Funktionalität der ChR2 Mutante ChR2(L132C) mit erhöhter Ca2+-Permeabilität im Tandem Protein tCXCR4/CatCh nachgewiesen. Auch die Internalisierung von tCXCR4/CatCh konnte anhand der zeitabhängigen Abnahme des CatCh-Signals nach der CXCR4-Aktivierung durch SDF1 in Strommessungen beobachtet werden. Für tCXCR4/Arch, ein Tandem Protein mit einer Protonenpumpe, wurde die SDF1-induzierte Internalisierung mit Hilfe der konfokalen Laser-Scanning-Mikroskopie betrachtet und eine Kolokalisierung der Fluoreszenz des im Tandem exprimierten YFP und der eines gelabelten CXCR4-spezifischen Antikörpers in intrazellulären Vesikeln beobachtet. Bei Behandlung mit dem CXCR4 Antagonisten AMD3100 wurde die Kolokalisierung hauptsächlich in der Zellmembran festgestellt, da die Internalisierung blockiert war. Die Tandem Protein könnten als in intrazellulären Organellen wirkende optogenetische Werkzeuge eingesetzt werden für z.B. die Manipulation der intrazellulären Ca2+-Konzentration.
Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before. Therefore, we applied the pan-HDAC inhibitors (HDACi) trichostatin A (TSA) and suberoylanilide hydroxamic acid (SAHA) as well as HDAC-specific siRNA. Administration of HDACi reduced HDAC activity and decreased expression of IKKε although its acetylation was increased. Other pro-inflammatory genes (IL-1β, iNOS, TNFα) also decreased while COX-2 expression increased. HDAC 2, 3 and 4, respectively, might be involved in IKKε and iNOS downregulation with potential participation of NF-κB transcription factor inhibition. Suppression of HDAC 1–3, activation of NF-κB and RNA stabilization mechanisms might contribute to increased COX-2 expression. In conclusion, our results indicate that TSA and SAHA exert a number of histone- and HDAC-independent functions. Furthermore, the data show that different HDAC enzymes fulfill different functions in macrophages and might lead to both pro- and anti-inflammatory effects which have to be considered in therapeutic approaches.
Simple Summary: Targeted therapies are of growing interest to physicians in cancer treatment. These drugs target specific genes and proteins involved in the growth and survival of cancer cells. Brain tumor therapy is complicated by the fact that not all drugs can penetrate the blood brain barrier and reach their target. We explored the non-invasive method, Magnetic Resonance Spectroscopy, for monitoring drug penetration and its effects in live animals bearing brain tumors. We were able to show the presence of the investigated drug in mouse brains and its on-target activity.
Abstract: Background: BAY1436032 is a fluorine-containing inhibitor of the R132X-mutant isocitrate dehydrogenase (mIDH1). It inhibits the mIDH1-mediated production of 2-hydroxyglutarate (2-HG) in glioma cells. We investigated brain penetration of BAY1436032 and its effects using 1H/19F-Magnetic Resonance Spectroscopy (MRS). Methods: 19F-Nuclear Magnetic Resonance (NMR) Spectroscopy was conducted on serum samples from patients treated with BAY1436032 (NCT02746081 trial) in order to analyze 19F spectroscopic signal patterns and concentration-time dynamics of protein-bound inhibitor to facilitate their identification in vivo MRS experiments. Hereafter, 30 mice were implanted with three glioma cell lines (LNT-229, LNT-229 IDH1-R132H, GL261). Mice bearing the IDH-mutated glioma cells received 5 days of treatment with BAY1436032 between baseline and follow-up 1H/19F-MRS scan. All other animals underwent a single scan after BAY1436032 administration. Mouse brains were analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). Results: Evaluation of 1H-MRS data showed a decrease in 2-HG/total creatinine (tCr) ratios from the baseline to post-treatment scans in the mIDH1 murine model. Whole brain concentration of BAY1436032, as determined by 19F-MRS, was similar to total brain tissue concentration determined by Liquid Chromatography with tandem mass spectrometry (LC-MS/MS), with a signal loss due to protein binding. Intratumoral drug concentration, as determined by LC-MS/MS, was not statistically different in models with or without R132X-mutant IDH1 expression. Conclusions: Non-invasive monitoring of mIDH1 inhibition by BAY1436032 in mIDH1 gliomas is feasible.
Background: The ERGO2 (Ernaehrungsumstellung bei Patienten mit Rezidiv eines Glioblastoms) MR-spectroscopic imaging (MRSI) subtrial investigated metabolism in patients randomized to calorically restricted ketogenic diet/intermittent fasting (crKD-IF) versus standard diet (SD) in addition to re-irradiation (RT) for recurrent malignant glioma. Intracerebral concentrations of ketone bodies (KB), intracellular pH (pHi), and adenosine triphosphate (ATP) were non-invasively determined. Methods: 50 patients were randomized (1:1): Group A keeping a crKD-IF for nine days, and Group B a SD. RT was performed on day 4-8. Twenty-three patients received an extended MRSI-protocol (1H decoupled 31P MRSI with 3D chemical shift imaging (CSI) and 2D 1H point-resolved spectroscopy (PRESS)) at a 3T scanner at baseline and on day 6. Voxels were selected from the area of recurrent tumor and contralateral hemisphere. Spectra were analyzed with LCModel, adding simulated signals of 3-hydroxybutyrate (βOHB), acetone (Acn) and acetoacetate (AcAc) to the standard basis set. Results: Acn was the only reliably MRSI-detectable KB within tumor tissue and/or normal appearing white matter (NAWM). It was detected in 4/11 patients in Group A and in 0/8 patients in Group B. MRSI results showed no significant depletion of ATP in tumor tissue of patients at day 6 during crKD-IF, even though there were a significant difference in ketone serum levels between Group A and B at day 6 and a decline in fasting glucose in Group A from baseline to day 6. The tumor specific alkaline pHi was maintained. Conclusions: Our metabolic findings suggest that tumor cells maintain energy homeostasis even with reduced serum glucose levels and may generate additional ATP through other sources.r sources.
The compound class of the fabclavines was described as secondary or specialized metabolites (SM) for Xenorhabdus budapestensis and X. szentirmaii. Their corresponding structure was elucidated by NMR and further derivatives could be identified in both strains. Biochemically, fabclavines are hybrid SMs derived from two non-ribosomal-peptide-synthetases (NRPS), one type I polyketide-synthase (PKS) and polyunsaturated fatty acid (PUFA) synthases. In detail, a hexapeptide is connected via partially reduced polyketide units to an unsual polyamine. Structurally, they are related to the (pre-)zeamines, described for Serratia plymuthica and Dickeya zeae. Fabclavines exhibit a broad-spectrum bioactivity against a variety of different organisms like Grampositive and Gram-negative bacteria, fungi, protozoa but also against eukaryotic celllines.
In this work, the fabclavine biosynthesis was elucidated and assigned to two independently working assembly lines. The NRPS-PKS-pathway is initiated by the first NRPS FclI via generation of a tetrapeptide, which is elongated by the second NRPS FclJ, leading to a hexapeptide. Alternatively, FclJ can also act as direct start of the biosynthesis, resulting in the final formation of shortened fabclavine derivatives with a diinstead of a hexapeptide. In both cases, the peptide moiety is transferred to the iterative type I PKS FclK, leading to an elongation with partially reduced polyketide units. The resulting NRPS-PKS-intermediate is still enzyme-bound. The PUFA-homologues FclC, FclD and FclE in combination with FclF, FclG and FclH belong to the polyamine-forming pathway. Briefly, repeating decarboxylative Claisen thioester condensation reactions of acyl-coenzym A building blocks lead to the generation of an acyl chain in a PKS- or fatty acid biosynthesis-like manner. The corresponding β-keto-groups are either completely reduced or transaminated in a specific and repetitive way, resulting in the concatenation of so-called amine-units. The final β-keto-group is reduced to a hydroxy-group and the intermediate is reductively released by the thioester reductase FclG. A subsequent transamination step leads to the final polyamine. The NRPS-PKS- as well as the polyamine-pathway are connected by FclL. This condensation domain-like protein catalyzes the condensation of the polyamine with the NRPS-PKS-part, which results in the release of the final fabclavine. The results are described in detail in the first publication (first author).
Fabclavine biosynthesis gene cluster (BGC) are widely spread among the genus Xenorhabdus and Photorhabdus. In Xenorhabdus strains a high degree of conservation regarding the BGC synteny as well as the identity of single proteins can be observed. However, Photorhabdus strains harbor only the PUFA-homologues. While in Photorhabdus no product could be detected, our analysis revealed that the Xenorhabdus strains produce a large chemical diversity of different derivatives. Briefly, the general backbone of the fabclavines is conserved and only four chemical moieties are variable: The second and last amino acids of the NRPS-part, the number of incorporated polyketide units as well as the number of amine units in the polyamine. In combination with the elucidated biosynthesis, these variables could be assigned to single biosynthesis components as diversity mechanisms. Together with the 10 already described derivatives, a total of 32 derivatives could be detected. Interestingly, except for taxonomic closely related strains, all analyzed strains produce their own set of derivatives. Finally, we could confirm that the fabclavines are the major bioactive compound class in the analyzed strains under laboratory conditions. The results are described in detail in the second publication (first author).
Together with our collaboration partner Prof. Selcuk Hazir a potent bioactivity against Enterococcus faecalis, which is associated with endodontic infections, could be contributed to X. cabanillasii. Here, we could confirm that this bioactivity can be assigned to the fabclavines. The results are described in detail in the third publication(co-author).
Among the genus Xenorhabdus, X. bovienii represents an exception as its NRPS and PKS genes of the fabclavine BGC are missing or truncated, resulting in the exclusive production of polyamines. Furthermore, its PUFA-homologue FclC harbors an additional dehydratase (DH) domain. Upon extensive analysis a yet unknown deoxy-polyamine was identified and assigned to this additional domain. Finally, the DH domain was transferred into other polyamine pathways. Regardless of an in cis or in trans integration, the chimeric pathways produced deoxy-derivatives of its naturally occurring polyamines, suggesting that this represents another diversification mechanism. The results are described in detail in the attached manuscript (first author).
Objective: This study aims to evaluate catheter management in acute epididymitis (AE) patients requiring inpatient treatment and risk factors predicting severity of disease.
Material and Methods: Patients with diagnosed AE and inpatient treatment between 2004 and 2019 at the University Hospital Frankfurt were analyzed. A risk score, rating severity of AE, including residual urine > 100 ml, fever > 38.0°C, C-reactive protein (CRP) > 5 mg/dl, and white blood count (WBC) > 10/nl was introduced.
Results: Of 334 patients, 107 (32%) received a catheter (transurethral (TC): n = 53, 16%, suprapubic (SPC): n = 54, 16%). Catheter patients were older, exhibited more comorbidities, and had higher CRP and WBC compared with the non-catheter group (NC). Median length of stay (LOS) was longer in the catheter group (7 vs. 6 days, p < 0.001), whereas necessity of abscess surgery and recurrent epididymitis did not differ. No differences in those parameters were recorded between TC and SPC. According to our established risk score, 147 (44%) patients exhibited 0–1 (low-risk) and 187 (56%) 2–4 risk factors (high-risk). In the high-risk group, patients received a catheter significantly more often than with low-risk (TC: 22 vs. 9%; SPC: 19 vs. 12%, both p ≤ 0.01). Catheter or high-risk patients exhibited positive urine cultures more frequently than NC or low-risk patients. LOS was comparable between high-risk patients with catheter and low-risk NC patients.
Conclusion: Patients with AE who received a catheter at admission were older, multimorbid, and exhibited more severe symptoms of disease compared with the NC patients. A protective effect of catheters might be attributable to patients with adverse risk constellations or high burden of comorbidities. The introduced risk score indicates a possibility for risk stratification.
Background: Since January 2018 performance of urethroplasties is done on regular basis at the University Hospital Frankfurt (UKF). We aimed to implement and transfer an institutional standardized perioperative algorithm for urethral surgery (established at the University Hospital Hamburg-Eppendorf—UKE) using a validated Urethral Stricture Surgery Patient-Reported Outcome Measure (USS-PROM) in patients undergoing urethroplasty at UKF. Materials and Methods: We retrospectively analyzed all patients who underwent urethroplasty for urethral stricture disease between January 2018 and January 2020 at UKF. All patients were offered to revisit for clinical follow-up (FU) and completion of USS-PROM. Primary end point was stricture recurrence-free survival (RFS). Secondary endpoints were functional outcomes, quality of life (QoL), and patient satisfaction. Results: In total, 50 patients underwent urethroplasty and 74 and 24% had a history of previous urethrotomy or urethroplasty, respectively. A buccal mucosal graft urethroplasty was performed in 86% (n = 43). After patient's exclusion due to lost of FU, FU <3 months, and/or a pending second stage procedure, 40 patients were eligible for final analysis. At median FU of 10 months (interquartile-range 5.0–18.0), RFS was 83%. After successful voiding trial, the postoperative median Qmax significantly improved (24.0 vs. 7.0 mL/s; p < 0.01). Conversely, median residual urine decreased significantly (78 vs. 10 mL; p < 0.01). Overall, 95% of patients stated that QoL improved and 90% were satisfied by the surgical outcome. Conclusions: We demonstrated a successful implementation and transfer of an institutional standardized perioperative algorithm for urethral surgery from one location (UKE) to another (UKF). In our short-term FU, urethroplasty showed excellent RFS, low complication rates, good functional results, improvement of QoL and high patient satisfaction. PROMs allow an objective comparison between different centers.
Objective: To analyze the effect of adverse preoperative patient and tumor characteristics on perioperative outcomes of open (ORP) and robot-assisted radical prostatectomy (RARP).
Material and Methods: We retrospectively analyzed 656 patients who underwent ORP or RARP according to intraoperative blood loss (BL), operation time (OR time), neurovascular bundle preservation (NVBP) and positive surgical margins (PSM). Univariable and multivariable logistic regression models were used to identify risk factors for impaired perioperative outcomes.
Results: Of all included 619 patients, median age was 66 years. BMI (<25 vs. 25-30 vs. ≥30) had no influence on blood loss. Prostate size >40cc recorded increased BL compared to prostate size ≤ 40cc in patients undergoing ORP (800 vs. 1200 ml, p < 0.001), but not in patients undergoing RARP (300 vs. 300 ml, p = 0.2). Similarly, longer OR time was observed for ORP in prostates >40cc, but not for RARP. Overweight (BMI 25-30) and obese ORP patients (BMI ≥30) showed longer OR time compared to normal weight (BMI <25). Only obese patients, who underwent RARP showed longer OR time compared to normal weight. NVBP was less frequent in obese patients, who underwent ORP, relative to normal weight (25.8% vs. 14.0%, p < 0.01). BMI did not affect NVPB at RARP. No differences in PSM were recorded according to prostate volume or BMI in ORP or RARP. In multivariable analyses, patient characteristics such as prostate volume and BMI was an independent predictor for prolonged OR time. Moreover, tumor characteristics (stage and grade) predicted worse perioperative outcome.
Conclusion: Patients with larger prostates and obese patients undergoing ORP are at risk of higher BL, OR time or non-nervesparing procedure. Conversely, in patients undergoing RARP only obesity is associated with increased OR time. Patients with larger prostates or increased BMI might benefit most from RARP compared to ORP.
Introduction: There is still an ongoing debate whether a transrectal ultrasound (TRUS) approach for prostate biopsies is associated with higher (infectious) complications rates compared to transperineal biopsies. This is especially of great interests in settings with elevated frequencies of multidrug resistant organisms (MDRO).
Materials and Methods: Between 01/2018 and 05/2019 230 patients underwent a TRUS-guided prostate biopsy at the department of Urology at University Hospital Frankfurt. Patients were followed up within the clinical routine that was not conducted earlier than 6 weeks after the biopsy. Among 230 biopsies, 180 patients took part in the follow-up. No patients were excluded. Patients were analyzed retrospectively regarding complications, infections and underlying infectious agents or needed interventions.
Results: Of all patients with follow up, 84 patients underwent a systematic biopsy (SB) and 96 a targeted biopsy (TB) after MRI of the prostate with additional SB. 74.8% of the patients were biopsy-naïve. The most frequent objective complications (classified by Clavien-Dindo) lasting longer than one day after biopsy were hematuria (17.9%, n = 32), hematospermia (13.9%, n = 25), rectal bleeding (2.8%, n = 5), and pain (2.2%, n = 4). Besides a known high MDRO prevalence in the Rhine-Main region, only one patient (0.6%) developed fever after biopsy. One patient each (0.6%) consulted a physician due to urinary retention, rectal bleeding or gross hematuria. There were no significant differences in complications seen between SB and SB + TB patients. The rate of patients who consulted a physician was significantly higher for patients with one or more prior biopsies compared to biopsy-naïve patients.
Conclusion: Complications after transrectal prostate biopsies are rare and often self-limiting. Infections were seen in <1% of all patients, regardless of an elevated local prevalence of MDROs. Severe complications (Clavien-Dindo ≥ IIIa) were only seen in 3 (1.7%) of the patients. Repeated biopsy is associated with higher complication rates in general.