Time Trends in Causes of Death in People with HIV: Insights from the Swiss HIV Cohort Study.

BACKGROUND: Advancements in access to antiretroviral therapy (ART) and human immunodeficiency virus (HIV) care have led to a decline in acquired immunodeficiency syndrome (AIDS)-related deaths among people with HIV (PWH) in Switzerland. However, data on the ongoing changes in causes of death among PWH over the past 15 years is scarce. METHODS: We investigated all reported deaths in the Swiss HIV Cohort Study between 2005-2022. Causes of death were categorized using the Coding Causes of Death in HIV protocol. The statistical analysis included demographic stratification to identify time trends and logistic regression models to determine associated factors for the underlying cause of death. RESULTS: In total, 1630 deaths were reported, with 23.7% of individuals assigned female at birth. Out of these deaths, 147 (9.0%) were HIV/AIDS-related, 373 (22.9%) due to non-AIDS, non-hepatic (NANH) cancers, 166 (10.2%) liver-related, and 158 (9.7%) cardiovascular-related. The median age at death increased from 45.0 [40.0,53.0] years in 2005-2007 to 61.0 [56.0,69.5] years in 2020-2022. HIV/AIDS and liver-related causes of death decreased, whereas deaths from NANH cancers increased, and cardiovascular-related deaths remained relatively stable. CONCLUSION: The proportionally decreasing HIV/AIDS and liver-related deaths showcase the effectiveness of ART, comprehensive HIV patient care, and interventions targeting hepatitis C virus co-infection. Future research should focus on managing cancer and cardiovascular-related conditions as the new leading causes of death among PWH. Comprehensive healthcare strategies focusing on non-AIDS-related comorbidities, cancer management, and sustaining liver and cardiovascular health are needed to bridge the ongoing health disparities between PWH and the general population.

Chemsex drugs on the rise: a longitudinal analysis of the Swiss HIV Cohort Study from 2007 to 2017.

OBJECTIVES: Chemsex refers to the use of sex-enhancing drugs among men who have sex with men (MSM) in combination with specific sexual and social behaviours. Longitudinal data on this development and the associated health risks are scarce. METHODS: Data on all recreational drugs reported in the Swiss HIV Cohort Study (SHCS) from 2007 to 2017 were collected. Drug use was analysed longitudinally for all drug classes. In addition, potential associations between patient characteristics and the consumption of methamphetamine, γ-hydroxybutric acid/γ-butyrolactone (GHB/GBL), 3,4-methylenedioxymethamphetamine (MDMA/XTC), cocaine and amphetamine were analysed. RESULTS: We analysed 166 167 follow-up entries for 12 527 SHCS participants, including 7101 free text field entries containing information about recreational drugs other than cannabis, cocaine and heroin. Overall, we observed a stable percentage (9.0%) of recreational drug use (excluding cannabis, amyl nitrite and prescription drugs). For MSM, however, there was an increase in overall drug use from 8.8% in 2007 to 13.8% in 2017, with particularly large increases for methamphetamine (from 0.2 to 2.4%; P < 0.001) and GHB/GBL (from 1.0 to 3.4%; P < 0.001). The use of each of the potentially sex-enhancing drugs methamphetamine, GHB/GBL, cocaine, XTC/MDMA and amphetamine was significantly associated with condomless sex with nonsteady partners, and higher prevalences of depression, syphilis and hepatitis C. CONCLUSIONS: The significant increase in the use of chemsex drugs among MSM in the SHCS and the strong association with coinfections and depression highlights the need for harm reduction programmes tailored to MSM. According to our results, improving knowledge about recreational drugs is important for all health care professionals working with people living with HIV.

[Robot-assisted kidney transplantation]. / Roboterassistierte Nierentransplantation.

BACKGROUND: Robot-assisted surgery has become widely adopted in urology due to advantages in comparison with laparoscopic or open approaches. Robot-assisted living kidney transplantation is one of the most challenging procedures in urology regarding technical, but also psychological and ethical aspects, and is currently routinely performed in two German departments. OBJECTIVES: The goal was to analyze and compare current evidence and experiences of robot-assisted living kidney transplantation in Europe and in Germany. MATERIALS AND METHODS: A systematic search was performed to identify relevant publications. They were compared with latest results from two German academic centers (Halle and Homburg/Saar). RESULTS: In 2015, robot-assisted living kidney transplantation was performed for the first time in Europe. Since then, 8 academic centers have established this procedure. Until today, more than 180 robot-assisted kidney transplantations have been performed. Short- and mid-term results have proven to be excellent with low complication rates. Apart from 3 transplant losses because of arterial thrombosis and 5 surgical re-explorations due to hematoma, no other noteworthy complications occurred. There was only 1 lymphocele. The median blood loss was 150 ml and kidney function after 1 year was unchanged in comparison with postoperative day 30. CONCLUSIONS: Robot-assisted living kidney transplantation is not inferior to the open approach. Even superiority is not unlikely because problematic situations such as obese patients or complex vascular anatomy can be handled safely. In particular, the development of lymphocele and wound healing disorders appear to be significantly decreased compared to conventional surgery.

[Trivialization of prostate cancer? : Stage shift and possible causes]. / Bagatellisierung des Prostatakarzinoms? : Stadien-Shift und mögliche Ursachen.

BACKGROUND: According to the strongly negative grade D recommendation of the U.S. Preventive Services Task Force in 2012, the prostate-specific antigen (PSA) test was not only not recommended but was also warned against. As a result in the USA there was a stage shift towards more advanced tumor stages under the newly detected prostate cancers; however, in contrast to the highly questionable American PLCO study, the European ERSPC study showed a clear reduction in prostate cancer-related mortality. OBJECTIVE: In this patient cohort it was investigated whether the tumor stage distribution in curatively treated prostate cancer has significantly changed, whether this has an influence on the perioperative results and complication rates and how these changes could have occurred. MATERIAL AND METHODS: Patients after radical prostatectomy from 2008 to 2010 were compared to those from 2017. Demographic data, intraoperative courses, perioperative and postoperative complications and histopathological results were compared. RESULTS: A total of 1276 operations were analyzed. Preoperative PSA levels showed a significant increase in 2017 (10.5 ± 13.4 ng/ml vs. 8.4 ± 9.1 ng/ml, p = 0.032). The pathological staging revealed a 20% increase in T3 tumors (49.4% versus 29.0%, p < 0.001). Correspondingly, moderately and poorly differentiated cancers and therefore those with higher aggressiveness were significantly more frequent with 11.2% (p < 0.001) and 10.4% (p < 0.001), respectively. The number of patients with lymph node metastases at prostatectomy even increased fourfold (4.5% vs. 16.9%, p < 0.001). CONCLUSION: In the radical prostatectomy group, there was a shift to unfavorable and metastatic tumor stages. This negative trend seems largely to be caused by a lower acceptance of early detection by means of PSA determination.

Survival outcomes in patients with large (≥7cm) clear cell renal cell carcinomas treated with nephron-sparing surgery versus radical nephrectomy: Results of a multicenter cohort with long-term follow-up.

BACKGROUND: Does the dogma of nephron sparing surgery (NSS) still stand for large renal masses? Available studies dealing with that issue are considerably biased often mixing imperative with elective indications for NSS and also including less malignant variants or even benign renal tumors. Here, we analyzed the oncological long-term outcomes of patients undergoing elective NSS or radical tumor nephrectomy (RN) for non-endophytic, large (≥7cm) clear cell renal carcinoma (ccRCC). METHODS: Prospectively acquired, clinical databases from two academic high-volume centers were screened for patients from 1980 to 2010. The query was strictly limited to patients with elective indications. Surgical complications were retrospectively assessed and classified using the Clavien-Dindo-classification system (CDS). Overall survival (OS) and cancer specific survival (CSS) were analyzed using the Kaplan-Meier-method and the log-rank test. RESULTS: Out of in total 8664 patients in the databases, 123 patients were identified (elective NSS (n = 18) or elective RN (n = 105)) for ≥7cm ccRCC. The median follow-up over all was 102 months (range 3-367 months). Compared to the RN group, the NSS group had a significantly longer median OS (p = 0.014) and median CSS (p = 0.04). CONCLUSIONS: In large renal masses, NSS can be performed safely with acceptable complication rates. In terms of long-term OS and CSS, NSS was at least not inferior to RN. Our findings suggest that NSS should also be performed in patients presenting with renal tumors ≥7cm whenever technically feasible. Limitations include its retrospective nature and the limited availability of data concerning long-term development of renal function in the two groups.

Rapid decline of anti-hepatitis C virus (HCV) antibodies following early treatment of incident HCV infections in HIV-infected men who have sex with men.

OBJECTIVES: Following clearance of incident hepatitis C virus (HCV) infections, HCV antibody levels may decline, resulting in seroreversion. It is unclear to what extent HCV antibody level trajectories differ between patients with treatment-induced sustained virological response (SVR), those with spontaneous clearance and those with untreated replicating HCV infection. We investigated HCV antibody level dynamics in HIV-infected MSM with different clinical outcomes. METHODS: We investigated anti-HCV antibody level dynamics following an incident HCV infection in 67 HIV-infected men who have sex with men (MSM) with different clinical outcomes: SVR (n = 33), spontaneous clearance (n = 12), and untreated replicating infection (n = 22). Antibody levels were measured at the time of HCV diagnosis, and at yearly intervals for 3 years thereafter. RESULTS: At baseline, median HCV antibody levels were similar in the three groups: 13.4, 13.8 and 13.5 sample to cut-off (S/CO) for SVR, spontaneous clearance and untreated infection, respectively. Over 3 years of follow-up, SVR was associated with a more pronounced decrease in anti-HCV levels compared with spontaneous clearance and untreated infection [median decline 71% [interquartile range (IQR: 43-87%), 38% (IQR: 29-60%) and 12% (IQR: 9-22%), respectively; P < 0.001]. Seroreversions occurred in five of 33 (15%) patients with SVR and in one of 12 (8%) with spontaneous clearance. A shorter delay between time of infection and treatment start correlated with higher rates of decline in antibody levels. Seven patients experienced a reinfection. CONCLUSIONS: Treatment-induced HCV clearance was associated with a more pronounced decline in anti-HCV antibody levels and with higher rates of seroreversion compared with spontaneous clearance or untreated replicating HCV infection among HIV-infected MSM with incident HCV infections. Rapid clearance of HCV RNA following early HCV treatment might impair the development of persistent antibody titres.

Robot-sewn ileoileal anastomosis during robot-assisted cystectomy.

PURPOSE: To analyze the feasibility and perioperative results of patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. METHODS: This is a mono-centric analysis of perioperative data from 48 consecutive patients undergoing robot-assisted cystectomy with intracorporeal urinary diversion and robot-sewn ileoileal anastomosis. Data include the preoperative variables, operative and postoperative course and complication rates related to bowel anastomosis. End points were time spent for anastomosis and intra- and postoperative complication rates. RESULTS: Median operating time was 23.0 (13-60) min for the ileoileal anastomosis. Median overall operating time was 295 (200-780) min, with a median of 282 (200-418) min and 414.0 (225-780) min for the ileum conduit (N = 35) and ileal neobladder (N = 13). Two patients developed paralytic ileus; in another patient acute peritonitis occurred, but was caused by urinary leakage and therefore unrelated to the bowel anastomosis. No anastomotic leakage was noticed. Costs for the robot-sewn anastomosis was 8€ compared to 1250€ for a stapled anastomosis which was performed in previous cases. Limitations are the non-comparative nature of the analysis and the limited number of patients. CONCLUSIONS: Robot-sewn ileoileal anastomosis is feasible with low complication rates. Compared to the stapled anastomosis, a robot-sewn ileoileal anastomosis may serve as an alternative and cost-saving approach.

On the potential of a short-term intensive intervention to interrupt HCV transmission in HIV-positive men who have sex with men: A mathematical modelling study.

Increasing access to direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection and decelerating the rise in high-risk behaviour over the next decade could curb the HCV epidemic among HIV-positive men who have sex with men (MSM). We investigated if similar outcomes would be achieved by short-term intensive interventions like the Swiss-HCVree-trial. We used a HCV transmission model emulating two 12-months intensive interventions combining risk counselling with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA treatment for HCV genotypes 1 and 4 (replicating the Swiss-HCVree-trial). To capture potential changes outside intensive interventions, we varied time from HCV infection to treatment in clinical routine and overall high-risk behaviour among HIV-positive MSM. Simulated prevalence dropped from 5.5% in 2016 to ≤2.0% over the intervention period (June/2016-May/2017) with the pangenotypic intervention, and to ≤3.6% with the Swiss-HCVree-trial. Assuming time to treatment in clinical routine reflected reimbursement restrictions (METAVIR ≥F2, 16.9 years) and stable high-risk behaviour in the overall MSM population, prevalence in 2025 reached 13.1% without intensive intervention, 11.1% with the pangenotypic intervention and 11.8% with the Swiss-HCVree-trial. If time to treatment in clinical routine was 2 years, prevalence in 2025 declined to 4.8% without intensive intervention, to 2.8% with the pangenotypic intervention, and to 3.5% with the Swiss-HCVree-trial. In this scenario, the pangenotypic intervention and the Swiss-HCVree-trial reduced cumulative (2016-2025) treatment episodes by 36% and 24%, respectively. Therefore, intensive interventions could reduce future HCV treatment costs and boost the benefits of long-term efforts to prevent high-risk behaviour and to reduce treatment delay. But if after intensive interventions treatment is deferred until F2, short-term benefits of intensive interventions would dissipate in the long term.

[Is there still a role for active surveillance in prostate cancer?] / Hat Active Surveillance beim Prostatakarzinom noch einen Stellenwert?

Long-term data demonstrate a higher oncological risk associated with active surveillance (AS) than initially anticipated. In particular, patients with more than two tumor-involved biopsy cores and/or Gleason-7a foci must be regarded as having an increased risk of developing an incurable stage of disease after an initial attempt of AS. For patients with Gleason-7a foci, the 15-year risk of suffering from an incurable tumor stage is reported as high as 60%. Furthermore, life expectancy must be regarded as one of the major risk factors to finally develop symptomatic incurable disease. A discussion has therefore started as to whether a high life expectancy should be regarded as an exclusion criterion against AS. An estimated life expectancy exceeding 15 or 20 years has been proposed for patients suffering from Gleason 7a or 6 foci at initial biopsy, respectively. Furthermore, it must be expected that a number of molecular risk factors will gain importance in the near future for the decision-making process for or against AS.

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials.

BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan-Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model. RESULTS: Baseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56-0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48-0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40-0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49-0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups. CONCLUSION: OS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis. CLINICAL TRIALS NUMBER: COU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).