Danijel Kivaranovic

Long-term outcome of the adjustable transobturator male system (ATOMS): results of a European multicentre study.

To evaluate the long‐term effectiveness and safety of the adjustable transobturator male system (ATOMS®, Agency for Medical Innovations A.M.I., Feldkirch, Austria) in a European‐wide multicentre setting.

Renal replacement therapy in critically ill liver cirrhotic patients – Outcome and Clinical Implications

Current guidelines discourage renal replacement therapy (RRT) in critically ill cirrhotics in the lack of liver transplant (LT) options. This study aimed to identify patients who benefit from RRT in the short and long‐term.

Risk Factors for Treatment Failure With the Adjustable Transobturator Male System Incontinence Device: Who Will Succeed, Who Will Fail? Results of a Multicenter Study

OBJECTIVE To identify risk factors for treatment failure of men with the adjustable transobturator male system (ATOMS) for treating stress urinary incontinence (SUI). PATIENTS AND METHODS Sixty-two patients with SUI after prostate surgery were provided with an ATOMS. The self-defined criteria for treatment failure (implant removal [A], no improvement or ≥3 pads/24 hours [B], and no improvement or ≥150 mL urine loss/24 hours [C]) were compared to anamnestic, clinical, and time-specific parameters: age, Charlson comorbidity index (CCI), urine culture (UC), previous ineffective implants, body mass index, radiotherapy, renal function (serum creatinine), smoker status, urethral strictures, SUI severity, surgery time, time to and season at implantation, and port system application. RESULTS After a median follow-up of 17.7 months, 9 ATOMS (15%) were removed due to infection (8) or dysfunction (1); 23% and 16% had treatment failure of criteria B and C. Dry rate/overall success rate was 61%/87%. Age alone was no risk factor but the CCI and a positive UC were univariate significant predictors of the criteria A, B, and C. Besides, previous devices and renal failure were significantly associated with implant removal (A) and SUI severity with criterion C. In multivariate analysis, previous devices (P = .0163), positive UC (P = .0190), and SUI severity (P = .0123) were the strongest predictors of A, B, and C, respectively. CONCLUSION A poor CCI, preoperative positive UC, severe SUI, and previous implants lead to more treatment failure and removal. Age, body mass index, radiotherapy, urethral strictures, current smoking, time-specific parameters, seasonality, and port system application did not influence the outcome.

Sexuality and erectile function after implantation of an Adjustable Transobturator Male System (ATOMS) for urinary stress incontinence. A multi-institutional prospective study

OBJECTIVES To investigate erectile function and sexuality before/after implantation of the ATOMS device including continence outcome, pain perception and co-morbidities. MATERIALS AND METHODS We collected data from 34 patients (2010-2014) who were provided with an ATOMS implant due to mild or moderate stress urinary incontinence (SUI) after radical prostatectomy (RPE), transurethral resection (TURP) or radiotherapy. Previous failed implants were no contraindication. Sexuality was evaluated with the International Index of Erectile Function (IIEF-5). The Visual Analog Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used to analyse pain perception. Results regarding continence, influence of co-morbidities and drug intake were interpreted. RESULTS IIEF-5 score increased 6 months after ATOMS implantation with a mean difference of 2.18 (Cl: 1.22, 3.14), p < 0,001). Non-sexually active patients had the greatest benefit. However, 50% of patients achieved a mean IIEF-5 of 10.1 and 38% of patients reported a new onset of sexual activity at follow up (mean IIEF-5 score of 12.9). This is in accordance with reduced SUI and absence of persistent pain syndrome. Overall success rate regarding 24h pad-use was 88% (no pad rate 38%). Previous failed implants did not influence results but diabetes, obesity and drug intake (beta-blockers, antidepressants) led to poorer outcomes. CONCLUSION Sexuality and erectile function improves significantly 6 months after ATOMS implantation. We postulate that reduced SUI (also during sexual activity) and absence of chronic pain are the improving factors. ATOMS should be offered to men with mild to moderate SUI who are interested in regaining their erectile function and sexual activity.

Primary preventive cardioverter-defibrillator implantation (Pro-ICD) in patients awaiting heart transplantation. A prospective, randomized, controlled 12-year follow-up study

The aim of this study was to evaluate whether short‐term primary preventive cardioverter‐defibrillator (ICD) implantation as bridge to heart transplantation (HTX) provides any survival benefit. Thirty‐three patients awaiting HTX were randomized to either conventional therapy (control group) or primary preventive ICD implantation (ICD group). Fourteen patients had ischemic cardiomyopathy (ICM) and 19 patients had dilated cardiomyopathy (DCM). Sixteen patients were randomized to the ICD group and 17 patients were randomized to the control group. Twenty patients (61%) were transplanted after a waiting time of 10 ± 9 months. The remaining 13 patients (39%) were not transplanted because of clinical improvement (n = 5), cerebral hemorrhage (n = 3), or death (n = 5). On the waiting list, 3 ICD patients with DCM developed slow VTs without ICD intervention, two patients with ICM (6%) had fast VT terminated by the ICD, and no arrhythmic death was observed. After 11.9 years (median), 13 of 20 HTX patients (65%) and 5 of 13 non‐HTX patients (38%) were alive. Survivors had a higher LVEF (22 ± 6 vs. 17 ± 4%, P = 0.0092) and a better exercise capacity (75 ± 29 vs. 57 ± 24 Watt, P = 0.0566) at baseline as compared to nonsurvivors. This study may not support the general use of primary preventive ICDs as a short‐term bridge to heart transplantation.

Non-linear significant relationship between use of glycopeptides and isolation of vancomycin-resistant Enterococcus species in a university hospital setting

BackgroundEmergence of colonization and infection with vancomycin-resistant enterococci (VRE) has become a worldwide challenge. To investigate whether the increasing incidence of VRE isolation can be correlated with use of glycopeptides in the hospital setting, we conducted a hospital-wide two-year study in the university hospital of Vienna.MethodsWithin the period from January 2011 through December 2012 all patients with isolation of invasive or non-invasive VRE were retrospectively included. Specialty-specific data concerning the consumption of vancomycin and teicoplanin, fluoroquinolones and third generation cephalosporins in defined daily doses (DDDs) from June 2010 through May 2012 were extracted from the hospital pharmacy computer system. To assess the relationship between the usage of those antibiotics and the incidence of VRE (VRE-rate per 10 000 patients) a Poisson regression was performed.FindingsIn the study period 266 patients were colonized or infected with VRE. Specialty-specific VRE isolation was as follows: general surgical units (44 patients), bone marrow transplant unit (35 patients), general medical units (33 patients), cardiothoracic surgery (27 patients), nephrology (26 patients), haematooncology (22 patients), gastroenterology (17 patients), urology (17 patients), and the infectious diseases unit (11 patients). Hospital-wide consumption of glycopeptides was higher for teicoplanin than for vancomycin (26 242 versus 8677 DDDs). Specialty-specific VRE incidence significantly increased with the use of glycopeptides, fluoroquinolones or third generation cephalosporins (p < 0.001). The results of the Poisson regression for vancomycin (p = 0.0018) and teicoplanin (p < 0.0001) separately were both highly significant. Spearman’s correlation coefficient indicated a strong correlation between the two variables (rho = 0.8).ConclusionOverall usage of glycopeptides, fluoroquinolones or third generation cephalosporins contributed to the emergence of VRE in the hospital setting.

Impact of extracorporeal shockwave therapy on tooth mobility in adult orthodontic patients: a randomized single‐center placebo‐controlled clinical trial

AIM This RCT investigated the effect of non-invasive extracorporeal shockwaves on tooth mobility in orthodontic patients after active treatment. MATERIALS AND METHODS Seventy-two adult patients were included in the study. Immediately after active orthodontic treatment, patients were assigned to a treatment or a placebo group based on block randomization. The orthodontic patients were required to be otherwise healthy. The region of interest was the anterior portion of the mandible. The treatment group received a single shockwave treatment with 1000 impulses while the placebo group was treated with an acoustic sham. Tooth mobility was evaluated over a period of 6 months using a Periotest and manual testing. Pocket probing depths, bleeding on probing and the irregularity index were also assessed. RESULTS Tooth mobility reduced significantly over 6 months in both groups, but shockwaves achieved significantly more rapid reduction on manual testing. Probing depth was significantly reduced while the irregularity index remained stable. Bleeding on probing was significantly reduced in the treatment group. No anti-inflammatory effect could be derived due to possible initial group differences. CONCLUSIONS The mobility of teeth aligned by orthodontic treatment reduces over time. Shockwave treatment appeared to reduce tooth mobility more rapidly.

Circulating endothelial progenitor cells in castration resistant prostate cancer: a randomized, controlled, biomarker study.

Background Endothelial progenitor cells (CEPs) and circulating endothelial cells (CECs) are potential biomarkers of response to anti-angiogenic treatment regimens. In the current study, we investigated the effect of docetaxel and sunitinib on CEP/CEC kinetics and clinical response in castration resistant prostate cancer (CRPC) patients. Patients and methods Chemonaive patients with CRPC were enrolled in this study to receive either sunitinib (37.5 mg/d), in combination with docetaxel (75 mg/m2) or docetaxel alone. CEP and CEC kinetics were analyzed for every cycle. The primary objective was to compare CEP/CEC pharmacodynamics between both treatment arms. We also investigated if CEC/CEP spikes, induced by MTD docetaxel, are suppressed by sunitinib in patients treated with docetaxel/sunitinib relative to docetaxel monotherapy. Results A total of 27 patients were enrolled. We observed a significant increase of CEP/CEC (total/viable) counts over time within each cycle (coefficients 0.29233, 0.22092 and 0.26089, respectively; p<0.001). However, no differences between the treatment groups, in terms of CEP and CEC kinetics, were detected. In the docetaxel monotherapy arm 4 (30%) patients responded to therapy with a 50% PSA decline, while 9 (64%) patients showed a PSA decline in the combination group (n.s.). The median PFS in the docetaxel monotherapy group was 3.1 months (2.6–3.6 months, 95% CI) and 6.2 months (4.9–7.4 months, 95% CI; p = 0.062) in the combination arm. Sunitinib/docetaxel was reasonably well tolerated and toxicity manageable. Conclusion In summary, no significant differences in CEC and CEP kinetics between the treatment arms were observed, although a highly significant increase of CEPs/CECs within each cycle over time was detected. These results mirror the challenge we have to face when employing anti-angiogenic strategies in CRPC. Additional preclinical research is needed to elucidate the underlying molecular mechanisms. However, docetaxel/sunitinib therapy resulted in a better response in terms of PSA decline and a trend towards improved PFS. Trial Registery clinicaltrialsregister.eu EudraCT 2007-003705-27

Prostate-specific Antigen Parameters and Prostate Health Index Enhance Prostate Cancer Prediction With the In-bore 3-T Magnetic Resonance Imaging-guided Transrectal Targeted Prostate Biopsy After Negative 12-Core Biopsy

OBJECTIVE To assess prostate cancer (PCa) detection and prediction by combining the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) with prostate-specific antigen (PSA) parameters and the Prostate Health Index (PHI) in case of negative 12-core standard biopsy. MATERIALS AND METHODS A total of 112 men (2014-2016) underwent 3-T multiparametric magnetic resonance imaging and subsequent MRGB of Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3-5. Ancillary PSA parameters (PSA ratio [%fPSA] and PSA density [PSAD]) and the PHI and PHI density (PHID) were recorded. With these parameters in combination with MRGB, PCa prediction was calculated. RESULTS The most common lesions biopsied were PI-RADS 4 (66%), located in the peripheral zone (64%), in the middle (58%) and anterior (65%) sections of the prostate, and 13 mm (IQR 10-15) in size. PCa was found in 62 (55%) patients (28% Gleason score ≥7). PSAD (0.15 vs 0.21; P = .0051), %fPSA (16 vs 13; P = .0191), PHI (45 vs 69; P < .0001), PHID (0.7 vs 1.5; P < .0001), and prostate volume (56 mL vs 45 mL; P = .0073) were significantly different in patients with PCa and those without PCa. PHI and PHID were the strongest predictors of PCa with areas under the curve of 0.79 and 0.77, respectively. Using optimal thresholds of 59 and 0.79, PHI and PHID were 69% and 84% sensitive and 82% and62% specific for PCa, respectively. CONCLUSION Following negative standard biopsy of the prostate, the MRGB achieved an overall PCa detection rate of 55% in patients with PI-RADS 3-5 lesions. By considering PHI and PHID, 82% and 62% of unnecessary biopsies could have been avoided, failing to detect 31% and 16% of cancers.

The non-invasive serum biomarker soluble Axl accurately detects advanced liver fibrosis and cirrhosis

Soluble Axl (sAxl) was recently shown to be strongly released into the blood during liver fibrogenesis and hepatocellular carcinoma suggesting sAxl as a biomarker of liver diseases. In this study we are the first to evaluate sAxl in human serum in comparison to Enhanced Liver Fibrosis (ELF) test and transient elastography (TE; Fibroscan) for its value to detect significant (F≥2), advanced fibrosis (F≥3), and cirrhosis (F4) in different liver disease etiologies and healthy controls. To properly determine the diagnostic accuracy of sAxl, a test cohort as well as a validation cohort was employed using liver biopsy as a reference method. Most notably, sAxl was confirmed to be an accurate biomarker of liver fibrosis and cirrhosis. Its accuracy was increased, if total serum albumin was added to build a sAxl/albumin ratio. Thereby an AUC of 0.763, 0.776, 0.826, and 0.832 was achieved corresponding to histological fibrosis stages F≥2, F≥3, F4 with liver biopsy as a reference method, and cirrhosis according to imaging techniques, respectively. With a cut-off of 1.29, a sensitivity, specificity, PPV, and NPV of 78.5%, 80.1%, 44%, 94.9% for the detection of cirrhosis was achieved. In comparison, ELF test and TE showed an AUC of 0.910, and 0.934, respectively, for the detection of cirrhosis. However, performance of TE was not possible in 14.4% of patients and both, ELF™ test and TE bear the disadvantage of high costs. In conclusion, the sAxl/albumin ratio is suggested as an accurate biomarker of liver fibrosis and cirrhosis. Due to its easy applicability and low costs it is suitable as screening parameter for significant to advanced liver fibrosis and cirrhosis, especially if TE is not available or not applicable.