Decoding myofibroblast origins in human kidney fibrosis.

Kidney fibrosis is the hallmark of chronic kidney disease progression; however, at present no antifibrotic therapies exist1-3. The origin, functional heterogeneity and regulation of scar-forming cells that occur during human kidney fibrosis remain poorly understood1,2,4. Here, using single-cell RNA sequencing, we profiled the transcriptomes of cells from the proximal and non-proximal tubules of healthy and fibrotic human kidneys to map the entire human kidney. This analysis enabled us to map all matrix-producing cells at high resolution, and to identify distinct subpopulations of pericytes and fibroblasts as the main cellular sources of scar-forming myofibroblasts during human kidney fibrosis. We used genetic fate-tracing, time-course single-cell RNA sequencing and ATAC-seq (assay for transposase-accessible chromatin using sequencing) experiments in mice, and spatial transcriptomics in human kidney fibrosis, to shed light on the cellular origins and differentiation of human kidney myofibroblasts and their precursors at high resolution. Finally, we used this strategy to detect potential therapeutic targets, and identified NKD2 as a myofibroblast-specific target in human kidney fibrosis.

Gender gap at a large European urological congress: still at the beginning.

PURPOSE: Women are underrepresented at scientific conferences, decreasing the visibility of female role models, which are vital for aspiring young female scientists. This investigation aimed to evaluate female representation at the German Society of Urology's (GSoU) annual meeting. METHODS: The programs of the GSoU meeting of 2011, 2018, 2019 and the virtual conference in 2020 were retrospectively quantified by gender and categorized by chair or speaker, type, and topic of the session. Descriptive analysis was applied. Univariate and multivariate analyses were performed to identify gender inequity and variables influencing gender distribution. A p value of < 0.05 was considered significant. RESULTS: A total of 2.504 chairs and speakers were invited to the GSoU meeting in 2018 and 2019. Female speakers or chairs were represented in 17.8%, indicating a gender gap of 64.7%. There were significant differences between session type, topic, and gender distribution for chairs and speakers. The topic surgical techniques were independent variables for both, underrepresented female chairs and speakers, respectively (p < 0.001). Vocational policy and plenary session were not represented by any female chair in 2011, 2018, and 2019. In comparison, the gender gap in 2011 was 74.2%, indicating a gap reduction of 1.2% per year. In a selected virtual program in 2020, the gender gap increased to 70.4%. CONCLUSION: There is still a significant discrepancy between gender representation at the GSoU annual meetings, and gender equity is currently not expected before 50 years. Future efforts should address the implementation of established guidelines for achieving gender equity at urological conferences.

Permanent Flank Bulge after Flank Incision: Patient- and Physician-Reported Outcome.

INTRODUCTION: The aim of this study was to determine the incidence and risk factors for postoperative flank bulging and associated physiologic/psychologic consequences as well as to establish a clinical flank bulge classification system after open retroperitoneal surgery. METHODS: In this retrospective study, a postal patient survey was sent to 240 patients who underwent open retroperitoneal surgery between 2007 and 2017. Patients, who reported a flank bulge, were invited for further evaluation, which included a clinical examination and standardized photo documentation. RESULTS: Forty-three of 120 patients (35.8%) reported a flank bulging after retroperitoneal surgery. During clinical examination, a flank bulge could be confirmed in 25 patients, whereas in 18 patients, no bulging could be detected, leading to a corrected rate of flank bulge-positive patients of 20.8%. The corresponding relaxation values ranged from 1 to 1.44 and correlated with the clinical degree of bulging. A body mass index of ≥25 was identified as a risk factor. No correlation was found regarding age, gender, surgery side, access to the retroperitoneum, surgical procedure, and pathology. Thirty-seven patients complained about chronic pain or suffered from the cosmetic impact of bulging. Thirteen of those patients had shown a flank bulge during clinical examination, resulting in a symptomatic bulge rate of 10.8% (13/120 patients). CONCLUSION: Chronic pain and postoperative flank bulging are 2 of the most common long-term complications after open retroperitoneal access. If an open retroperitoneal approach is required, particularly obese patients should be thoroughly informed about the risk of flank bulging and chronic pain.

Comparative Analysis of Guideline Adherence between Germany and Austria by Using the Example of Uncomplicated Urinary Tract Infections.

BACKGROUND: Medical guidelines represent the evidence-based state of the art of their scientific field. They aim to guide decisions for physicians and patients about appropriate health care for specific clinical circumstances. However, guideline recommendations are often not adhered to in clinical practice. In particular, a large discrepancy exists regarding the treatment of uncomplicated urinary tract infections. To date, just a few studies addressed the potential reasons for these guideline violations. OBJECTIVES: This investigation aimed to identify and complement reasons for the nonadherence to guideline recommendations. METHODS: A survey amongst a total of 563 German and Austrian urologists identified physician- and patient-related factors contributing to this current state. RESULTS: The physician's personal experience, the lack of applicability to individual patients, and shortage of time were identified as crucial barriers for the physician. Patient-related barriers were poor experience with the antibiotic, fear of collateral damage, and inadequate information about the disease and its therapy. CONCLUSIONS: We suggest modifying guideline designs by including abstracts and flowcharts appropriate for daily use and separate patient instructions to improve guideline compliance. Furthermore, guideline authors should communicate updates in a timely and accessible manner. Presentations at scientific congresses increase visibility and enhance the dialogue with colleagues.

Significance of Hyperbaric Oxygenation in the Treatment of Fournier's Gangrene: A Comparative Study.

INTRODUCTION: Hyperbaric oxygenation (HBO), in addition to anti-infective and surgical therapy, seems to be a key treatment point for Fournier's gangrene. The aim of this study was to investigate the influence of HBO therapy on the outcome and prognosis of Fournier's gangrene. PATIENTS AND METHODS: In the present multicenter, retrospective observational study, we evaluated the data of approximately 62 patients diagnosed with Fournier's gangrene between 2007 and 2017. For comparison, 2 groups were distinguished: patients without HBO therapy (group A, n = 45) and patients with HBO therapy (group B, n = 17). The analysis included sex, age, comorbidities, clinical symptoms, laboratory and microbiological data, debridement frequency, wound dressing, antibiotic use, outcome and prognosis. The statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA). RESULTS: Demographic data showed no significant differences. The laboratory parameters C-reactive protein and urea were significantly higher in group B (group B: 301.7 vs. 140.6 mg/dL; group A: 124.8 vs. 54.7 mg/dL). Sepsis criteria were fulfilled in 77.8 and 100% of the patients in groups A and B respectively. Treatment in the intensive care unit (ICU) was therefore indicated in 69% of the patients in group A and 100% of the patients in group B. The mean ICU stay was 9 and 32 days for patients in groups A and B respectively. The wound debridement frequency and hospitalization stay were significantly greater in group B (13 vs. 5 debridement and 40 vs. 22 days). Initial antibiosis was test validated in 80% of the patients in group A and 76.5% of the patients in group B. Mortality was 0% in group B and 4.4% in the group A. CONCLUSION: The positive influence of HBO on the treatment of Fournier's gangrene can be estimated only from the available data. Despite poorer baseline findings with comparable risk factors, mortality was 0% in the HBO group. The analysis of a larger patient cohort is desirable to increase the significance of the results.

[Acute genital diseases]. / Akute Genitalerkrankungen.

Acute genital diseases can occur at any age and are characterized by complaints of various kinds of the external genitalia. Pain, swelling, and redness of the scrotum, adjacent groin region, and immediate surroundings are the leading symptoms, the severity of which may vary. In addition, peritonitic symptoms such as nausea, vomiting, and circulatory sensations may be present and are comparable to symptoms of an acute abdomen. The term "acute scrotum" encompasses various clinical entities, where scrotal symptoms are predominant and represent a urological emergency situation. Immediate and comprehensive diagnostics are necessary to ensure timely management in case of necessary surgical intervention.

[Experiences from the commission of experts]. / Erfahrungen aus der Gutachterkommission.

The task of the commission of experts on medical errors is to provide a neutral and independent assessment of a treatment for which a physician is responsible and evaluate the liability issue. The objective evaluation is intended to make it easier for the person whose health has been damaged by a treatment error to assert justified claims and for the physician to reject unfounded accusations. The aim is to promote amicable dispute resolution. For the legal classification of the term "complication", a definition is necessary. The physician understands this to mean a deviation from the actual course and consequences of treatment. The lawyer sees a complication as an undesirable consequence of incorrect patients' information or treatment. One-third of all court cases end with a finding of medical malpractice. This rate corresponds to the medical malpractice rate in medical malpractice litigation. If medical malpractice is found, the physician's liability insurance is contacted to settle the claim. If the commission of experts denies medical malpractice, the patient usually refrains from taking legal action.

[Position paper of the working group Urological Acute Medicine]. / Positionspapier des Arbeitskreises "Urologische Akutmedizin".

Emergency patients with acute genitourinary system diseases are frequently encountered in both outpatient and clinical emergency structures. It is estimated that one-third of all inpatients in a urology clinic initially present as an emergency. In addition to general emergency medicine knowledge, specialized urologic expertise is a prerequisite for the care of these patients, which is needed early and specifically for optimal treatment outcomes. It must be taken into account that, on the one hand, the current structures of emergency care still lead to delays in patient care despite positive developments in recent years. On the other hand, most hospital emergency facilities need urologic expertise on site. In addition, politically intended changes in our health care system, which drive an increasing ambulantization of medicine and condition a further centralization of emergency clinics, become effective. The aim of the newly established working group "Urological Acute Medicine" is to ensure and further improve the quality of care for emergency patients with acute genitourinary system diseases and, in consensus with the German Society of Interdisciplinary Emergency and Acute Medicine, to define precise task distributions and interfaces of both specialities.

[Importance of HPV status and p16 for the prognosis of penile carcinoma]. / Bedeutung von HPV-Status und p16 für die Prognose des Peniskarzinoms.

BACKGROUND: Penile cancer is a rare but often lethal tumour disease, especially in the metastatic stage. Most data on prognostic factors for penile cancer are based on small patient cohorts, and even meta-analyses are mostly limited in terms of patient numbers. There is a lack of sufficient parameters to predict the metastatic risk of these tumours. Furthermore, the role of the HPV status for the prognosis, and, in this regard, of p16INK4a is still unclear. MATERIAL AND METHODS: In this study, 236 patients from an international multicentre cohort were analysed with regard to histological subtypes, HPV and p16 status, and other clinical parameters. The HPV status was only graded as HPV-positive if HPV was detected by PCR and the p16 status defined by immunochemistry was positive. The statistical analysis was carried out using the Kaplan-Meier method as well as the log-rank test and a univariable and multivariable analysis using the Cox regression model. RESULTS: A positive HPV status was not a significant parameter for either metastasis-free (MFS), tumour-specific (CSS) or overall survival (OS). p16-positive tumours showed a significantly better MFS (p=0.026), which was also confirmed in the subgroup analysis of HPV-negative tumours (p=0.037) without differences in CSS or OS. In the usual type, there was also a trend towards an improved MFS, but without statistical significance (p=0.070). p16-positive tumours were associated with a highly significantly better MFS (hazard ratio 0.3; p=0.004) in the multivariable Cox regression, while patients with a pT1b tumour stage or advanced lymph node metastasis showed a significantly worse survival. In the multivariable analysis of HPV-negative tumours, p16 status was also confirmed as an independent predictor of MFS (Hazard ratio 0.2; p=0.007). CONCLUSION: HPV status alone seems to be lacking prognostic relevance. In contrast, p16 status was confirmed as an independent prognostic factor. Thus, the expression of p16INK4a is associated with a significantly better MFS. Especially in HPV-negative tumours, the p16 status should be evaluated with regard to the prognostic value and thus also with a view to the treatment decision.

Evaluation of Prognostic Parameters to Identify Aggressive Penile Carcinomas.

BACKGROUND: Advanced penile carcinoma is characterized by poor prognosis. Most data on prognostic factors are based on small study cohorts, and even meta-analyses are limited in patient numbers. Therefore, there is still a lack of evidence for clinical decisions. In addition, the most recent TNM classification is questionable; in line with previous studies, we found that it has not improved prognosis estimation. METHODS: We evaluated 297 patients from Germany, Russia, and Portugal. Tissue samples from 233 patients were re-analyzed by two experienced pathologists. HPV status, p16, and histopathological parameters were evaluated for all patients. RESULTS: Advanced lymph node metastases (N2, N3) were highly significantly associated with reductions in metastasis-free (MFS), cancer-specific (CS), and overall survival (OS) rates (p = <0.001), while lymphovascular invasion was a significant parameter for reduced CS and OS (p = 0.005; p = 0.007). Concerning the primary tumor stage, a significant difference in MFS was found only between pT1b and pT1a (p = 0.017), whereas CS and OS did not significantly differ between T categories. In patients without lymph node metastasis at the time of primary diagnosis, lymphovascular invasion was a significant prognostic parameter for lower MFS (p = 0.032). Histological subtypes differed in prognosis, with the worst outcome in basaloid carcinomas, but without statistical significance. HPV status was not associated with prognosis, either in the total cohort or in the usual type alone. CONCLUSION: Lymphatic involvement has the highest impact on prognosis in penile cancer, whereas HPV status alone is not suitable as a prognostic parameter. The pT1b stage, which includes grading, as well as lymphovascular and perineural invasion in the T stage, seems questionable; a revision of the TNM classification is therefore required.

Adult human kidney organoids originate from CD24+ cells and represent an advanced model for adult polycystic kidney disease.

Adult kidney organoids have been described as strictly tubular epithelia and termed tubuloids. While the cellular origin of tubuloids has remained elusive, here we report that they originate from a distinct CD24+ epithelial subpopulation. Long-term-cultured CD24+ cell-derived tubuloids represent a functional human kidney tubule. We show that kidney tubuloids can be used to model the most common inherited kidney disease, namely autosomal dominant polycystic kidney disease (ADPKD), reconstituting the phenotypic hallmark of this disease with cyst formation. Single-cell RNA sequencing of CRISPR-Cas9 gene-edited PKD1- and PKD2-knockout tubuloids and human ADPKD and control tissue shows similarities in upregulation of disease-driving genes. Furthermore, in a proof of concept, we demonstrate that tolvaptan, the only approved drug for ADPKD, has a significant effect on cyst size in tubuloids but no effect on a pluripotent stem cell-derived model. Thus, tubuloids are derived from a tubular epithelial subpopulation and represent an advanced system for ADPKD disease modeling.

A single center prospective study: prediction of postoperative general quality of life, potency and continence after radical retropubic prostatectomy.

PURPOSE: We investigated the importance of patient and tumor characteristics to predict continence, potency, and physical and mental health 1 year after radical prostatectomy. MATERIALS AND METHODS: This prospective study included 236 patients who underwent open radical retropubic prostatectomy at a single institution between January 2005 and October 2007. We used validated questionnaires, including the Short Form General Health Survey, the International Index of Erectile Function and the International Consultation of Incontinence Questionnaire, to evaluate postoperative health related quality of life, erectile function and continence, respectively. Questionnaires were completed at months 3, 6 and 12 postoperatively. RESULTS: At 1-year followup 75%, 73%, 75% and 26% of patients had returned to baseline physical health, mental health, continence and potency, respectively. Mental health recovered more slowly than physical health. Preoperative prostate specific antigen less than 20 ng/ml, nerve sparing technique, no intraoperative or postoperative complications, no adjuvant treatment and attendance at a postoperative rehabilitation program were significant factors that positively influenced the outcome in regard to health related quality of life, and postoperative potency and continence (p <0.05). CONCLUSIONS: Predictors can be used when counseling patients who are preparing themselves for radical retropubic prostatectomy. This study highlights the mental impact of this surgery on these patients. We propose that men should undergo a combined mental and physical counseling program before surgery to predict postoperative health related quality of life, potency and continence after radical retropubic prostatectomy.

[Urological emergency management : Detection and treatment]. / Management urologischer Notfälle : Erkennen und Behandeln.

As a result of the restructuring of emergency care provided by statutory health insurance companies and demographic change, the number of people presenting to emergency departments in hospitals is continuously increasing. A significant proportion of these emergencies concern the specialist discipline of urology. The clinical manifestations in emergency medical care range from trauma-related injuries to the urogenital tract and urinary transport disorders to hematuria and life-threatening infections. Due to the high incidence of urological tumors and the urogenital tract's affection in other malignant diseases, oncological patients are also frequently affected by urological emergencies. Fast and efficient diagnostic and therapeutic action is crucial in these situations to achieve an optimal treatment result.

[Contemporary practice patterns in the treatment of Fournier's gangrene in German academic medicine and their implications for planning a registry study]. / Behandlungssituation der Fournier-Gangrän an deutschen Universitätskliniken ­ eine nationale Umfrage zur Deskription aktueller Standards und resultierende Implikationen zur Planung einer Registerstudie.

BACKGROUND: Fournier's gangrene (FG) is a sporadic and life-threatening disease, but the outcome has not improved in recent years. OBJECTIVES: The primary aim of this study was the description of current practice patterns in German academic medicine. The secondary aim was the identification of factors associated with a higher mortality rate. Furthermore, the data will be used for the planning of a registry study. MATERIALS AND METHODS: A 29-item nonvalidated questionnaire was sent to German University Medical Centers (Department of Urology), including three reminders from April through June 2020. Data management and analysis were performed with SPSS 26.0. RESULTS: The response rate was 88.9%. A median of 5 patients (median age 60.0 years) with FG were treated annually in German University Medical Centers. The contemporary practice patterns are very heterogeneous, especially in terms of empirical antibiotic treatment. Only one significant risk factor for a mortality rate higher than 20.0% was identified-intensive care treatment for ≥10 days (p = 0.039). In addition, 50% stated that outcome of FG has not improved in recent years. Furthermore, the majority of the respondents think that mortality is still too high. Consequently, 84.4% support a registry study. From the answers to the open questions we received a variety of suggestions for planning such a study, e.g., histological confirmation of the disease. CONCLUSION: Treatment of FG is currently very heterogeneous. Furthermore, treatment outcomes are often unacceptable and difficult to predict.

Contemporary Outcomes after Transurethral Procedures for Bladder Neck Contracture Following Endoscopic Treatment of Benign Prostatic Hyperplasia.

OBJECTIVES: Bladder neck contracture (BNC) is a bothersome complication following endoscopic treatment for benign prostatic hyperplasia (BPH). The objective of our study was to give a more realistic insight into contemporary endoscopic BNC treatment and to evaluate and identify risk factors associated with inferior outcome. MATERIAL AND METHODS: We identified patients who underwent transurethral treatment for BNC secondary to previous endoscopic therapy for BPH between March 2009 and October 2016. Patients with vesico-urethral anastomotic stenosis after radical prostatectomy were excluded. Digital charts were reviewed for re-admissions and re-visits at our institutions and patients were contacted personally for follow-up. Our non-validated questionnaire assessed previous urologic therapies (including radiotherapy, endoscopic, and open surgery), time to eventual further therapy in case of BNC recurrence, and the modality of recurrence management. RESULTS: Of 60 patients, 49 (82%) and 11 (18%) underwent transurethral bladder neck resection and incision, respectively. Initial BPH therapy was transurethral resection of the prostate (TURP) in 54 (90%) and holmium laser enucleation of the prostate (HoLEP) in six (10%) patients. Median time from prior therapy was 8.5 (IQR 5.3-14) months and differed significantly in those with (6.5 months; IQR 4-10) and those without BNC recurrence (10 months; IQR 6-20; p = 0.046). Thirty-three patients (55%) underwent initial endoscopic treatment, and 27 (45%) repeated endoscopic treatment for BNC. In initially-treated patients, time since BPH surgery differed significantly between those with a recurrence (median 7.5 months; IQR 6-9) compared to those treated successfully (median 12 months; IQR 9-25; p = 0.01). In patients with repeated treatment, median time from prior BNC therapy did not differ between those with (4.5 months; IQR 2-12) and those without a recurrence (6 months; IQR 6-10; p = 0.6). Overall, BNC treatment was successful in 32 patients (53%). The observed success rate of BNC treatment was significantly higher after HoLEP compared to TURP (100% vs. 48%; p = 0.026). Type of BNC treatment, number of BNC treatment, and age at surgery did not influence the outcome. CONCLUSIONS: A longer time interval between previous BPH therapy and subsequent BNC incidence seems to favorably affect treatment success of endoscopic BNC treatment, and transurethral resection and incision appear equally effective. Granted the relatively small sample size, BNC treatment success seems to be higher after HoLEP compared to TURP, which warrants validation in larger cohorts.

[Bilateral vesicoureteral reflux: pro intravesical techniques]. / Bilateraler Reflux ­ pro intravesikale Techniken.

All surgical techniques in antireflux surgery are characterised by a high success rate of over 90 %. The common goal of all procedures is the formation of a submucosal tunnel which is four times longer than the diameter of the ureter. Successful treatment has been achieved worldwide with the extravesical antireflux technique according to Lich-Gregoir in non-dilated ureters and psoas hitch ureterocystoneostomy in dilated ureters. Intravesical surgical procedures include the Politano-Leadbetter technique and Cohen's cross-trigonal reimplantation. These open or laparoscopic/robotic standard procedures have higher rates of success than endoscopic subureteric injection.

Uni- vs. multiloculated pelvic lymphoceles: differences in the treatment of symptomatic pelvic lymphoceles after open radical retropubic prostatectomy.

PURPOSE: To evaluate the treatment of symptomatic pelvic lymphoceles (SPL) after performing radical retropubic prostatectomy (RRP) and pelvic lymphadenectomy (PLA) simultaneously. MATERIAL AND METHODS: We analyzed, in a retrospective study, 250 patients who underwent RRP with PLA simultaneously. Only patients with SPL were treated using different non- and invasive procedures such as percutaneous aspiration, percutaneous catheter drainage (PCD) with or without sclerotherapy, laparoscopic lymphocelectomy (LL) and open marsupialization (OM). RESULTS: Fifty-two patients (21%) had postoperative subclinical pelvic lymphoceles. Thirty patients (12%) developed SPL. Fifteen patients with noninfected uniloculated lymphocele (NUL) healed spontaneously after performing PCD. The remaining seven patients required sclerotherapy with additional doxycycline. After performing PCD, NUL healed better and faster than noninfected multiloculated lymphocele (NML) (success rate: 80% vs. 16%, respectively). Twenty-seven percent of patients treated initially with PCD, with or without sclerotherapy had persistent lymphocele. All patients were successfully treated with LL. Only one patient had an abscess as a major complication of a persistent SPL after PCD and sclerotherapy and was treated via an open laparotomy. CONCLUSIONS: Symptomatic NUL can be treated using PCD with or without sclerotherapy. If this therapy fails as first-line treatment, laparoscopic lymphocelectomy should be considered within a short period of time in order to achieve successful treatment. NML should be treated using a laparoscopic approach in centers where this type of expertise is available. Infected lymphoceles are drained externally. In these cases, percutaneous or open external drainage with adequate antibiotic coverage is preferable.

Quo Vadis Botulinum Toxin: Normative Constraints and Quality of Life for Patients With Idiopathic OAB?

Background: Idiopathic overactive bladder (iOAB), with or without urge incontinence (UI), has significant psychosocial effects on patients' quality of life (QoL). The first choice of treatment for iOAB is anticholinergics and, alternatively, the ß-3-adrenoceptor agonist mirabegron. However, systemic side effects and contraindications should be considered for both medications. Objective: We report the efficacy, safety and effects on QoL of botulinum toxin therapy (onabotulinum toxin type A, BOTOX®, Allergan) among patients with iOAB ± UI. Patients and Methods: Between 2005 and 2013, 51 patients were treated with onabotulinum toxin A (100 units). The inclusion criteria were the presence of confirmed iOAB ± UI with previous use of anticholinergic medication. Micturition frequency, pad count, postvoid residual volume and QoL were evaluated using two validated questionnaires [the Client Satisfaction Questionnaire-8 (CSQ-8) and the King's Health Questionnaire (KHQ)]. Statistical analysis was performed with SPSS 24.0 (p < 0.05). Results: After botulinum toxin injection, a significant improvement in iOAB ± UI symptoms was observed. The micturition frequency decreased from 10.4 ± 0.5 to 5.2 ± 0.4 micturitions per day (p = 0.026), and the pad count decreased from 3.6 ± 1.0 to 1.2 ± 0.3 pads per day (p = 0.033). Anticholinergics were not used during the administration of botulinum toxin therapy. Complications and postoperative need for intermittent self-catheterization (ISC) were not observed. Overall, 72 and 24% of patients reported being "satisfied" or "very satisfied" with the treatment. Additionally, 66% of patients would choose botulinum toxin again for the treatment of iOAB. Conclusion: Botulinum toxin therapy is an efficient, safe, and life-improving treatment for iOAB.

Desperate need for better management of Fournier's gangrene.

INTRODUCTION: To compare earlier and later patient groups with Fournier's gangrene, specifically with the incidence of rising antibiotic resistance rates in mind. Primary endpoints were to compare therapy, outcomes, and resistance rates. MATERIAL AND METHODS: A multicentric, retrospective, multi-national study was performed. Two groups with different time frames of treatment were defined: Group 1 (n = 50) and Group 2 (n = 104). Demographics and outcomes were analysed using Student-t test, chi-square test, or Fisher exact test. Survival data were estimated using the Kaplan Meier method and compared by Log rank testing. RESULTS: There were no significant demographic differences. Nor was there any significant difference in therapy or outcomes in the groups except for the duration of intensive care unit treatment, which lasted a mean 6.3 days in Group 1 and 11.5 days in Group 2 (p = 0.018). Survival time did not improve over the years (p = 0.268). We fortunately did not observe an increased rate of multi-resistant organisms (p = 1.000). This study's limitations are mainly due to its retrospective study design. CONCLUSIONS: Despite increasing antibiotic resistance rates worldwide, it was not apparent in our population. But the situation for these patients is alarming, since final outcome failed to improve over the last ten years despite more intensive critical-care therapy.