Microbial colonization and ureteral stent-associated storage lower urinary tract symptoms: the forgotten piece of the puzzle?

Purpose: Ureteral stents are frequently associated with side effects. Most patients suffer from storage lower urinary tract symptoms (LUTS). Storage LUTS are commonly attributed to the irritation of the trigone, smooth muscle spasm or a combination of factors. The relationship between microbial ureteral stent colonization (MUSC) and de novo or worsening storage LUTS has not been investigated yet. Methods: Five hundred ninety-one polyurethane ureteral stents from 275 male and 153 female patients were prospectively evaluated. The removed stents were sonicated to dislodge adherent microorganisms. Urine flow cytometry was performed to detect pyuria. A standardized urinary symptom questionnaire was given to all patients. Results: Thirty-five per cent of male and 28% of female cases showed de novo or worsened storage LUTS. MUSC was more common in patients with storage LUTS compared to patients without storage LUTS (men: 26 vs. 13%, respectively, P<0.05; women: 63 vs. 48%, respectively, P=0.13). Pyuria was significantly more common in patients with storage LUTS compared to patients without storage LUTS (men: 55 vs. 40%, respectively, P<0.05; women: 70 vs. 45%, respectively, P<0.05). No significant correlation was observed between the detected genera of microorganisms and storage LUTS. Conclusions: Our data show a significant association between MUSC- and stent-related de novo experienced or worsened storage LUTS in men. The incidence of MUSC is most common in both female and male patients with storage LUTS and accompanying pyuria. In these patients, a combination of antibiotics and anti-inflammatory drugs may be regarded as treatment optio

Microbial biofilm formation and catheter-associated bacteriuria in patients with suprapubic catheterisation

Purpose: Catheter-associated bacteriuria (CAB) with transurethral catheters is almost inevitable. Suprapubic catheters (SPCs) are widely considered to decrease the risk of CAB. However, SPCs are implants similarly prone to microbial biofilm formation. The spectrum of colonising pathogens has not been investigated. The aim of this prospective study was: (1) to assess the diversity of microbial suprapubic catheter colonisation (MSPCC), (2) to identify risk factors and (3) to investigate its association with CAB and catheter-associated urinary tract infection (CA-UTI). Methods: A total of 218 SPCs from 112 patients were studied. Urine specimens were obtained after device replacement or removal. Sonication was performed to dislodge adherent microorganisms. Data of patient sex, age, indwelling time, and underlying disease were recorded. Results: Sonicate-fluid culture (SFC) detected MSPCC in 95%. Increasing indwelling time correlated with MSPCC (p<0.05). Negative SFC was more frequent when antibiotic prophylaxis was applied at time of catheter placement (15 vs. 2%, p<0.05). Most commonly isolated were Enterobacteriaceae (45.8%), followed by Enterococcus spp. (25.7%) and Pseudomonas aeruginosa (10.3%). CAB and CA-UTI were observed in 95 and 11%, respectively. Conclusions: This study provides the first analysis of MSPCC. Indwelling time increases, whereas antibiotic prophylaxis decreases the risk of MSPCC. The spectrum of pathogens is comparable to the one obtained from urethral catheter biofilms. Urine specimens could not demonstrate the microbial diversity of MSPCC. SPCs are not preferable to urethral catheters to reduce CAB. Whether the risk of CA-UTI could be minimised by SPCs remains to be clarifie

Maximum tumor diameter adjusted to the risk profile predicts biochemical recurrence after radical prostatectomy

Currently, no consensus exists on the best method for tumor quantification in prostate cancer (PCA), and its prognostic value remains controversial. We evaluated how a newly defined maximum tumor diameter (MTD) might contribute to the prediction of biochemical recurrence (BCR) in a consecutive series of PCA patients treated with radical prostatectomy (RP). Patients with PCA who underwent RP without neoadjuvant therapy at a single center were included for analysis. MTD was defined as the largest diameter of all identified tumors in all three dimensions (i.e., length, width, or depth) of the prostate ("Basel technique”). Cox regression models addressed the association of MTD with BCR in three risk groups (low risk—prostate-specific antigen (PSA)  20ng/ml or pT3 or GS ≥ 8) and whole cohort. Within a median follow-up of 44months (interquartile range (IQR) 23-66), 48 patients (9.4%) in the intermediate-risk and high-risk groups experienced BCR. In multivariate Cox regression analysis, PSA, pathological stage (pT stage), GS, positive surgical margins (PSMs), and MTD > 19.5mm were independent predictors for BCR (p 24.5mm) was the only independent predictor of BCR in the intermediate-risk group (hazard ratio (HR) 9.933, 95% confidence interval (CI) 2.070-47.665; p < 0.05). MTD is an independent risk factor of BCR in PC patients after RP. The combination of the MTD with other well-known prognostic factors after RP may improve decision-making concerning follow-up intensity or adjuvant treatment

Prospective single-centre comparison of 120-W diode-pumped solid-state high-intensity system laser vaporization of the prostate and 200-W high-intensive diode-laser ablation of the prostate for treating benign prostatic hyperplasia

OBJECTIVE: To evaluate the safety, efficacy and short-term outcome of a new 980 nm high-intensity diode (HiDi) laser (Limmer Laser, Berlin, Germany) system in comparison to the diode-pumped solid-state laser high-performance system (HPS; GreenLight(TM), AMS, Minnetonka, MI, USA) for treating benign prostatic hyperplasia (BPH) in a prospective non-randomized single-centre study. PATIENTS AND METHODS: From February to September 2007, 117 consecutive patients with lower urinary tract symptoms secondary to BPH were included; 62 patients were treated with 120-W HPS laser vaporization and 55 with 980-nm HiDi laser ablation of the prostate. We evaluated perioperative variables, and complications during and after surgery. Patients presenting for follow-up completed the International Prostate Symptom Score, and had their maximum urinary flow rate and postvoid residual urine volume measured. RESULTS: The mean (sd) age of the patients was 72.3 (8.8) years (HiDi) and 73.1 (10.8) years (HPS), with a mean preoperative prostate volume of 64.7 (29.7) and 67.4 (46.9) mL, respectively. The mean operative duration was comparable, at 56.4 (20.2) and 62.7 (36.3) min, respectively, whereas the mean energy delivery was significantly higher with the diode laser, at 313 (132) vs 187 (129) kJ (P > 0.001). For patients treated with the HPS the rate of visual impairment from bleeding was higher (0% vs 12.9%, P > 0.01), as was prostate capsule perforation (0% vs 4.8%, P 0.05) was higher for the HiDi laser. During the follow-up there were higher rates of bladder neck stricture (14.5% vs 1.6%, P > 0.01), re-treatment (18.2% vs 1.6%, P > 0.01) and stress urinary incontinence (9.1% vs 0%; P > 0.05) for the HiDi laser group. CONCLUSION: Both systems investigated provide good tissue ablative properties. The HiDi laser at 980 nm is more favourable in terms of haemostasis. The penetration depths, resulting in coagulation necrosis and leading to increased re-treatment, bladder neck stricture and incontinence rates, were higher with the HiDi laser

Transcatheter mitral valve replacement or repair for secondary mitral regurgitation: a propensity score-matched analysis

Aims: This study aimed to compare outcomes after transcatheter mitral valve replacement (TMVR) and mitral valve transcatheter edge-to-edge repair (M-TEER) for the treatment of secondary mitral regurgitation (SMR). Methods and results: The CHOICE-MI registry included 262 patients with SMR treated with TMVR between 2014 and 2022. The EuroSMR registry included 1065 patients with SMR treated with M-TEER between 2014 and 2019. Propensity score (PS) matching was performed for 12 demographic, clinical and echocardiographic parameters. Echocardiographic, functional and clinical outcomes out to 1 year were compared in the matched cohorts. After PS matching, 235 TMVR patients (75.5 years [70.0, 80.0], 60.2% male, EuroSCORE II 6.3% [interquartile range 3.8, 12.4]) were compared to 411 M-TEER patients (76.7 years [70.1, 80.5], 59.0% male, EuroSCORE II 6.7% [3.9, 12.4]). All-cause mortality was 6.8% after TMVR and 3.8% after M-TEER at 30 days (p = 0.11), and 25.8% after TMVR and 18.9% after M-TEER at 1 year (p = 0.056). No differences in mortality after 1 year were found between both groups in a 30-day landmark analysis (TMVR: 20.4%, M-TEER: 15.8%, p = 0.21). Compared to M-TEER, TMVR resulted in more effective mitral regurgitation (MR) reduction (residual MR ≤1+ at discharge for TMVR vs. M-TEER: 95.8% vs. 68.8%, p < 0.001), and superior symptomatic improvement (New York Heart Association class ≤II at 1 year: 77.8% vs. 64.3%, p = 0.015). Conclusion: In this PS-matched comparison between TMVR and M-TEER in patients with severe SMR, TMVR was associated with superior reduction of MR and superior symptomatic improvement. While post-procedural mortality tended to be higher after TMVR, no significant differences in mortality were found beyond 30 days

Characteristics and Outcomes of Patients Screened for Transcatheter Mitral Valve Implantation: 1-Year Results from the CHOICE-MI Registry.

AIMS Transcatheter mitral valve implantation (TMVI) represents a novel treatment option for patients with mitral regurgitation (MR) unsuitable for established therapies. The CHOICE-MI registry aimed to investigate outcomes of patients undergoing screening for TMVI. METHODS AND RESULTS From 05/2014 to 03/2021, patients with MR considered suboptimal candidates for transcatheter edge-to-edge repair (TEER) and at high risk for mitral valve surgery underwent TMVI screening at 26 centres. Characteristics and outcomes were investigated for patients undergoing TMVI and for TMVI-ineligible patients referred to bailout-TEER, high-risk surgery or medical therapy (MT). The primary composite endpoint was all-cause mortality or heart failure hospitalisation after 1 year. Among 746 patients included (78.5 years [IQR 72.0-83.0], EuroSCORE II 4.7% [IQR 2.7-9.7]), 229 patients (30.7%) underwent TMVI with ten different dedicated devices. At 1 year, residual MR ≤1+ was present in 95.2% and the primary endpoint occurred in 39.2% of patients treated with TMVI. In TMVI-ineligible patients (N = 517, 69.3%), rates of residual MR ≤1+ were 37.2%, 100.0% and 2.4% after bailout-TEER, high-risk surgery and MT, respectively. The primary endpoint at 1 year occurred in 28.8% of patients referred to bailout-TEER, in 42.9% of patients undergoing high-risk surgery and in 47.9% of patients remaining on MT. CONCLUSION This registry included the largest number of patients treated with TMVI to date. TMVI with ten dedicated devices resulted in predictable MR elimination and sustained functional improvement at 1 year. In TMVI-ineligible patients, bailout-TEER and high-risk surgery represented reasonable alternatives, while MT was associated with poor clinical and functional outcomes. This article is protected by copyright. All rights reserved

Complement activation induces excessive T cell cytotoxicity in severe COVID-19

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated, CD16(+) T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16(+) T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16(+) T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16(+) cytotoxic T cells. Proportions of activated CD16(+) T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19

Complement activation induces excessive T cell cytotoxicity in severe COVID-19.

Severe COVID-19 is linked to both dysfunctional immune response and unrestrained immunopathology, and it remains unclear whether T cells contribute to disease pathology. Here, we combined single-cell transcriptomics and single-cell proteomics with mechanistic studies to assess pathogenic T cell functions and inducing signals. We identified highly activated CD16+ T cells with increased cytotoxic functions in severe COVID-19. CD16 expression enabled immune-complex-mediated, T cell receptor-independent degranulation and cytotoxicity not found in other diseases. CD16+ T cells from COVID-19 patients promoted microvascular endothelial cell injury and release of neutrophil and monocyte chemoattractants. CD16+ T cell clones persisted beyond acute disease maintaining their cytotoxic phenotype. Increased generation of C3a in severe COVID-19 induced activated CD16+ cytotoxic T cells. Proportions of activated CD16+ T cells and plasma levels of complement proteins upstream of C3a were associated with fatal outcome of COVID-19, supporting a pathological role of exacerbated cytotoxicity and complement activation in COVID-19