Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Purpose: To evaluate the morbidity, functional and oncological outcome of irreversible electroporation (IRE) as a focal therapy for prostate cancer (PCa) when used in “active surveillance (AS)” candidates refusing standard treatment options. Materials and Methods: IRE was performed under general anaesthesia, and the transurethral catheter was removed one day after intervention in all patients. Pre- and post-interventional voiding parameters (measured by International Prostate Symptom Score Questionnaire [IPSS], uroflowmetry and post-void residue) were compared. Follow-up (FU) was observed over a minimum of six months, including oncological outcome (controlled by multiparametric magnetic resonance imaging, rebiopsy, prostate-specific antigen dynamic as well as the need and type of secondary treatment) and general functional outcome (International Index of Erectile Function Questionnaire, satisfaction of the procedure). Results: Twenty-four patients refusing AS or standard treatment with a median FU of 18.7 months were included. IPSS showed nine patients with mild, 12 with moderate and two with severe obstructive voiding symptoms pre-intervention (focal IRE). Median IPSS pre-IRE was 9 points, 8.5 (p=0.341) at six months and 10 (p=0.392) after 12 months, respectively. Pre-IRE maximum urinary flow (Qmax) (median: 16.1±8.0 mL/sec) and Qmax after catheter removal (16.2±7.6 mL/sec) did not differ significantly (p=0.904). Thirteen PCa recurrences occurred (54.2%). Out-of-lesion-PCa was found in 12/13 patients (92.3%), while 4/13 patients showed in-lesion-PCa recurrence simultaneously (30.8%). In one patient, there was an in-lesion-PCa recurrence only (7.7%). Six out of 24 patients (25.0%) received a secondary treatment. All patients were satisfied with the IRE procedure. Conclusions Focal IRE underperforms regarding the overall oncological outcome and should not be offered as an equivalent therapy to established curative treatment strategies. Nevertheless, under a strict FU regimen, its lack of significant additional morbidity compared to an active surveillance strategy makes IRE a feasible alternative for low-risk PCa in highly selected patients as a personalised approach.

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton’s tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.
Antibodies, Monoclonal ; Immune System ; Immunocompromised Host ; JC Virus ; Leukemia, Lymphocytic, Chronic, B-Cell* ; Leukoencephalopathy, Progressive Multifocal* ; Protein-Tyrosine Kinases ; Rituximab

Emerging antibiotic resistance is a major global health threat. The analysis of nucleic acid sequences linked to susceptibility phenotypes facilitates the study of genetic antibiotic resistance determinants to inform molecular diagnostics and drug development. We collected genetic data (11,087 newly-sequenced whole genomes) and culture-based resistance profiles (10,991 out of the 11,087 isolates comprehensively tested against 22 antibiotics in total) of clinical isolates including 18 main species spanning a time period of 30 years. Species and drug specific resistance patterns were observed including increased resistance rates for Acinetobacter baumannii to carbapenems and for Escherichia coli to fluoroquinolones. Species-level pan-genomes were constructed to reflect the genetic repertoire of the respective species, including conserved essential genes and known resistance factors. Integrating phenotypes and genotypes through species-level pan-genomes allowed to infer gene-drug resistance associations using statistical testing. The isolate collection and the analysis results have been integrated into GEAR-base, a resource available for academic research use free of charge at https://gear-base.com.
Acinetobacter baumannii ; genetics ; isolation & purification ; Bacteria ; genetics ; isolation & purification ; Cell Culture Techniques ; methods ; Drug Resistance, Microbial ; genetics ; Escherichia coli ; genetics ; isolation & purification ; Genome, Bacterial ; Genotype ; Humans ; Internet ; Microbial Sensitivity Tests ; Phenotype ; Whole Genome Sequencing