Search

Background and purpose: Two novel enzyme replacement therapies (ERTs), studied in phase 3 trials in late-onset Pompe patients, reached marketing authorization by the European Medicines Agency in 2022 and 2023. The European Pompe Consortium (EPOC) updates and extends the scope of the 2017 recommendations for starting, switching and stopping ERT. Methods: The European Pompe Consortium consists of 25 neuromuscular and metabolic experts from eight European countries. This update was performed after an in-person meeting, three rounds of discussion and voting to provide a consensus recommendation. Results: The patient should be symptomatic, that is, should have skeletal muscle weakness or respiratory muscle involvement. Muscle magnetic resonance imaging findings showing substantial fat replacement can support the decision to start in a patient-by-patient scenario. Limited evidence supports switching ERT if there is no indication that skeletal muscle and/or respiratory function have stabilized or improved during standard ERT of 12 months or after severe infusion-associated reactions. Switching of ERT should be discussed on a patient-by-patient shared-decision basis. If there are severe, unmanageable infusion-associated reactions and no stabilization in skeletal muscle function during the first 2 years after starting or switching treatment, stopping ERT should be considered. After stopping ERT for inefficacy, restarting ERT can be considered. Six-monthly European Pompe Consortium muscle function assessments are recommended. Conclusions: The triple-S criteria on ERT start, switch and stop include muscle magnetic resonance imaging as a supportive finding and the potential option of home infusion therapy. Six-monthly long-term monitoring of muscle function is highly recommended to cover insights into the patient's trajectory under ERT.

Einleitung und Fragestellung: Emodin wird für Wirkungen von Pflanzenheilmitteln der traditionellen chinesischen Medizin verantwortlich gemacht. Anti-diabetische Effekte in Nagern wurden den unterschiedlichsten molekularen Wirkmechanismen zugeschrieben. Wir haben untersucht, wie weit die Verbesserung der Glukosehomöostase durch Emodin eine simple Folge von reduziertem Appetit und Körpergewicht sein könnte. Methodik: Emodin wurde der High Fat Diet adipöser Mäuse beigemischt (3 und 5 g/kg; Daten im Abstrakt beziehen sich auf die hohe Dosis). Als Kontrollen wurden nicht nur Mäuse mit freiem Zugang zu Futter verwendet, sondern auch solche, die durch eingeschränkte Fütterung die gleichen Gewichtskurven zeigten wie die Emodin-behandelten Tiere. Ergebnisse: Während 3 Wochen Emodinbehandlung (tägliche Aufnahme 229 mg/kg) war die Nahrungsaufnahme um 28% reduziert, was freilich eine entsprechende Wirkung auf die Gewichtszunahme hatte (−5% gegenüber +13% in Kontrollmäusen mit freiem Zugang zu Futter). Der Unterschied im Körpergewicht war, wie schon von anderen beschrieben, mit einer signifikanten Verbesserung der Glukosetoleranz verbunden (Reduktion der inkrementalen Fläche unter der Glukosekurve um 24%). Der Vergleich mit Kontrollmäusen mit gleicher Nahrungsaufnahme und gleichem Körpergewicht zeigte jedoch eine Emodin-induzierte signifikante Verschlechterung der Glukosetoleranz (inkrementale Glukosefläche um 54% größer). Ein Insulintoleranztest wies auf eine Emodin-bedingte Beeinträchtigung der Insulinsensitivität als mögliche Ursache hin. Schlussfolgerungen: Die Ergebnisse zeigen, dass die beschriebenen anti-diabetischen Effekte von Emodin in Nagern wohl nur die banale Folge von reduziertem Appetit sind, wie er durch sehr unspezifische Beeinträchtigungen, wie z. B. Übelkeit, hervorgerufen werden kann.

OBJECTIVES The use of multiparametric magnetic resonance imaging (mpMRI) has been widely adopted in the diagnostic work-up for suspicious prostate cancer (PCa) and is recommended in most current guidelines. However, mpMRI lesions are often indeterminate and/or turn out to be false-positive on prostate biopsy. The aim of this work was to evaluate Proclarix, a biomarker test for the detection of relevant PCa, regarding its diagnostic value in all men before biopsy and in men with indeterminate lesions on mpMRI (PI-RADS 3) during work-up for PCa. MATERIALS AND METHODS Men undergoing mpMRI-targeted and systematic biopsy of the prostate were prospectively enrolled. The Proclarix test was evaluated for the detection accuracy of clinically significant PCa (csPCa) defined as Grade Group ≥ 2 and its association to mpMRI results. Further, Proclarix's performance was also tested when adapted to prostate volume (Proclarix density) and performance compared to PSA density (PSAD). RESULTS A total of 150 men with a median age of 65 years and median PSA of 5.8 ng/mL were included in this study. CsPCa was diagnosed in 65 (43%) men. Proclarix was significantly associated with csPCa and higher PI-RADS score (p < 0.001). At the pre-defined cut-off of 10%, Proclarix's sensitivity for csPCa was 94%, specificity 19%, negative predictive value 80% and positive predictive value 47%. Proclarix density showed the highest AUC for the detection of csPCa of 0.77 (95%CI: 0.69-0.85) compared to PSA, PSAD and Proclarix alone. Proclarix was able to identify all six csPCa in men with PI-RADS 3 lesions (n = 28), whereas PSAD missed two out of six. At optimized cut-offs, Proclarix density outperformed PSAD by potentially avoiding 41% of unnecessary biopsies. CONCLUSION Proclarix demonstrates high sensitivity in detecting csPCa but may still result in unnecessary biopsies. However, Proclarix density was able to outperform PSAD and Proclarix and was found to be useful in men with PI-RADS 3 findings by saf

OBJECTIVES Active surveillance for low-risk prostate cancer closely monitors patients conservatively instead of the pursuit of active treatment to reduce overtreatment of insignificant disease. Since 2009, active surveillance has been recommended as the primary management option in the European Association of Urology guidelines for low-risk disease. The present study aimed to investigate the use and uptake of active surveillance over 10 years in our certified prostate cancer centre (University Hospital of Zurich) compared with those derived from the cancer registry of the canton of Zurich, Switzerland. MATERIALS AND METHODS We retrospectively identified all men diagnosed with low-risk prostate cancer at our institution and from the cancer registry of the canton of Zurich from 2009 to 2018. The primary treatment of each patient was recorded. Descriptive statistics were used to analyze the use of different treatments in our centre. The results were compared with those derived from the cancer registry. RESULTS A total of 3393 men with low-risk prostate cancer were included in this study (University Hospital of Zurich: n = 262; cancer registry: n = 3131). In the University Hospital of Zurich and cancer registry cohorts, 146 (55.7%) and 502 (16%) men underwent active surveillance, respectively. The proportions of local treatment [115 (43.9%) vs 2220 (71%)] and androgen deprivation therapy [0 (0%) vs 43 (1.4%)] were distinctly lower in the University Hospital of Zurich cohort than in the cancer registry cohort. The uptake of active surveillance over the years was high in the University Hospital of Zurich cohort (35.4% in 2009 and 88.2% in 2018) but only marginal in the cancer registry cohort (12.2% in 2009 and 16.2% in 2018). CONCLUSION Despite clear guideline recommendations, active surveillance for low-risk prostate cancer is still widely underused. Our analysis showed that access to a certified interdisciplinary tumour board significantly increases the use of active su

PURPOSE: Prostate-specific antigen (PSA) screening for men at risk of prostate cancer is controversial. The current recommendation is to raise awareness of prostate cancer and offer PSA screening in accordance with shared decision- making. Whether the possibility of a PSA screen is discussed with the patient depends on the treating physician, but data on physicians’ attitudes towards PSA screening are scarce. This study aimed to examine internists’ and urologists’ personal PSA screening activity as an indicator of their attitude towards PSA screening. MATERIALS AND METHODS: Members of the Swiss Society of Urology and the Swiss Society of General Internal Medicine were asked in 08/2020 to anonymously complete an online survey about personal PSA screening behaviour for themselves, their fathers, brothers and partners. Categorical and continuous variables were compared by chi-squared tests and t-tests, respectively. RESULTS: In total, 190/295 (response rate: 64%) urologists and 893/7400 (response rate: 12%) internists participated in the survey. Of the participants, 297/1083 (27.4%) were female. Male urologists >50 years of age screened themselves more often than male internists >50 years of age (89% vs 70%, p <0.05). Furthermore, urologists reported recommending screening statistically significantly more often than internists to their brother, father or partner regardless of their sex (men: 38.1% vs 18.5%; p <0.05; women: 81.8% vs 32.2%; p <0.05). CONCLUSIONS: Most participating male physicians >50 years of age have screened themselves for prostate cancer. Furthermore, PSA screening of relatives was significantly associated with the urology specialty. The reasons physicians screen themselves substantially more often than the public and why male and female urologists as well as male internists perform PSA screening more frequently in their private environment than female internists should be further examined.

Patients with non-muscle invasive (NMI) urothelial bladder cancer (BC) are at increased risk for the development of a secondary upper-urinary-tract urothelial carcinoma (UTUC). We aimed to assess the usefulness of routine upper-tract imaging surveillance during NMIBC follow-up in a patient cohort of a tertiary academic center. All routine upper-tract-imaging scans using computerized tomography urography (CTU) between 2003 and 2016 were assessed for UTUC detection. A total of 315 patients were analyzed. Initial tumor stage was Ta in 207 patients (65.7%), T1 in 98 patients (31.1%) and pure CIS in 10 patients (3.2%). A total of 149 (47.3%) presented with low-grade (LG), and 166 (52.7%) with high-grade (HG) disease. Median follow-up was 48 months (IQR: 55). Four patients (1.2%) were diagnosed with UTUC during follow-up. All four patients presented with initial Ta HG BC. Two of the patients (50%) were diagnosed by routine upper tract imaging. The other two patients were diagnosed after development of symptoms. The 5- and 10-year UTUC-free survival was 98.5% (standard error (SE) 0.9) and 97.6% (SE 1.3), respectively. UTUCs were detected exclusively in patients with initial HG disease, indicating that upper-tract surveillance might only be necessary in these patients.

Background: With the expanding indications and thus broader use of immune checkpoint inhibitors, clinicians are faced with a new kind of immune-related adverse events. Because of their immune modulating effects, immune checkpoint inhibitors have the potential to worsen autoimmunity in general. Paraneoplastic syndromes can be caused by tumor-induced autoimmune mechanisms. The use of immune-activating substances such as checkpoint inhibitors might lead to exacerbation of paraneoplastic syndromes causing premature discontinuation of the immunotherapy. Case presentation: We report on a 64-year-old patient with metastasized renal cell carcinoma who developed acute kidney failure after cytoreductive nephrectomy. Work-up revealed a paraneoplastic syndrome that caused tubulointerstitial nephritis (TIN). Glucocorticoid therapy successfully reversed the acute kidney injury. However, adjuvant therapy with Nivolumab provoked a flare-up of the paraneoplastic syndrome on two occasions, eventually leading to a treatment discontinuation. Conclusions: Many cases of Nivolumab-induced TIN have been described lately. However, our case demonstrates therapy failure due to a flare-up of a pre-existing paraneoplastic syndrome of the renal cancer. Against this background, it can only be speculated that some of the TIN cases discussed in prior literature might also have been flare-ups of subclinical autoimmunity.