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  • 1
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    Patients Regret Their Choice of Therapy Significantly Less Frequently after Robot-Assisted Radical Prostatectomy as Opposed to Open Radical Prostatectomy: Patient-Reported Results of the Multicenter Cross-Sectional IMPROVE Study
    MDPI AG ; 2022
    In:  Cancers Vol. 14, No. 21 ( 2022-10-30), p. 5356-
    Details
    In: Cancers, MDPI AG, Vol. 14, No. 21 ( 2022-10-30), p. 5356-
    Abstract: Patient’s regret (PatR) concerning the choice of therapy represents a crucial endpoint for treatment evaluation after radical prostatectomy (RP) for prostate cancer (PCA). This study aims to compare PatR following robot-assisted (RARP) and open surgical approach (ORP). A survey comprising perioperative-functional criteria was sent to 1000 patients in 20 German centers at a median of 15 months after RP. Surgery-related items were collected from participating centers. To calculate PatR differences between approaches, a multivariate regressive base model (MVBM) was established incorporating surgical approach and demographic, center-specific, and tumor-specific criteria not primarily affected by surgical approach. An extended model (MVEM) was further adjusted by variables potentially affected by surgical approach. PatR was based on five validated questions ranging 0–100 (cutoff 〉 15 defined as critical PatR). The response rate was 75.0%. After exclusion of patients with laparoscopic RP or stage M1b/c, the study cohort comprised 277/365 ORP/RARP patients. ORP/RARP patients had a median PatR of 15/10 (p 〈 0.001) and 46.2%/28.1% had a PatR 〉 15, respectively (p 〈 0.001). Based on the MVBM, RARP patients showed PatR 〉 15 relative 46.8% less frequently (p 〈 0.001). Consensual decision making regarding surgical approach independently reduced PatR. With the MVEM, the independent impact of both surgical approach and of consensual decision making was confirmed. This study involving centers of different care levels showed significantly lower PatR following RARP.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers14215356
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2527080-1
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  • 2
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    Patient’s Desire and Real Availability Concerning Supportive Measures Accompanying Radical Prostatectomy: Differences between Certified Prostate Cancer Centers and Non-Certified Centers Based on Patient-Reported Outcomes within the Cross-Sectional Study Improve
    MDPI AG ; 2023
    In:  Cancers Vol. 15, No. 10 ( 2023-05-19), p. 2830-
    Details
    In: Cancers, MDPI AG, Vol. 15, No. 10 ( 2023-05-19), p. 2830-
    Abstract: Certification as a prostate cancer center requires the offer of several supportive measures to patients undergoing radical prostatectomy (RP). However, it remains unclear how patients estimate the relevance of these measures and whether the availability of these measures differs between certified prostate cancer centers (CERTs) and non-certified centers (NCERTs). In 20 German urologic centers, a survey comprising questions on the relevance of 15 supportive measures was sent to 1000 patients at a median of 15 months after RP. Additionally, patients were asked to rate the availability of these measures using a four-item Likert scale. The aim of this study was to compare these ratings between CERTs and NCERTs. The response rate was 75.0%. In total, 480 patients underwent surgery in CERTs, and 270 in NCERTs. Patients rated 6/15 supportive measures as very relevant: preoperative medical counselling concerning treatment options, a preoperative briefing answering last questions, preoperative pelvic floor exercises (PFEs), postoperative PFEs, postoperative social support, and postoperative rehabilitation addressing physical fitness recovery. These ratings showed no significant difference between CERTs and NCERTs (p = 0.133–0.676). In addition, 4/9 of the remaining criteria were rated as more detailed by patients in CERTs. IMPROVE represents the first study worldwide to evaluate a patient-reported assessment of the supportive measures accompanying RP. Pertinent offers vary marginally between CERTs and NCERTs.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers15102830
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2527080-1
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  • 3
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    Local Anesthetic-Induced Central Nervous System Toxicity during Interscalene Brachial Plexus Block: A Case Series Study of Three Patients
    MDPI AG ; 2021
    In:  Journal of Clinical Medicine Vol. 10, No. 5 ( 2021-03-02), p. 1013-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 10, No. 5 ( 2021-03-02), p. 1013-
    Abstract: Local anesthetics are commonly administered by nuchal infiltration to provide a temporary interscalene brachial plexus block (ISB) in a surgical setting. Although less commonly reported, local anesthetics can induce central nervous system toxicity. In this case study, we present three patients with acute central nervous system toxicity induced by local anesthetics applied during ISB with emphasis on neurological symptoms, key neuroradiological findings and functional outcome. Medical history, clinical and imaging findings, and outcome of three patients with local anesthetic-induced toxic left hemisphere syndrome during left ISB were analyzed. All patients were admitted to our neurological intensive care unit between November 2016 and September 2019. All three patients presented in poor clinical condition with impaired consciousness and left hemisphere syndrome. Electroencephalography revealed slow wave activity in the affected hemisphere of all patients. Seizure activity with progression to status epilepticus was observed in one patient. In two out of three patients, cortical FLAIR hyperintensities and restricted diffusion in the territory of the left internal carotid artery were observed in magnetic resonance imaging. Assessment of neurological severity scores revealed spontaneous partial reversibility of neurological symptoms. Local anesthetic-induced CNS toxicity during ISB can lead to severe neurological impairment and anatomically variable cerebral lesions.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm10051013
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662592-1
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  • 4
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    Atrial Fibrillation and Transvenous Lead Extraction—A Comprehensive Subgroup Analysis of the GermAn Laser Lead Extraction RegistrY (GALLERY)
    MDPI AG ; 2022
    In:  Medicina Vol. 58, No. 11 ( 2022-11-21), p. 1685-
    Details
    In: Medicina, MDPI AG, Vol. 58, No. 11 ( 2022-11-21), p. 1685-
    Abstract: Background: Atrial fibrillation is the most common arrhythmia and has been described as driver of cardiovascular morbidity and risk factor for cardiac device-related complications, as well as in transvenous lead extraction (TLE). Objectives: Aim of this study was to characterize the procedural outcome and risk-factors of patients with atrial fibrillation (AF) undergoing TLE. Methods: We performed a subgroup analysis of all AF patients in the GALLERY (GermAn Laser Lead Extraction RegistrY) database. Predictors for all-cause mortality were assessed. Results: A total number of 510 patients with AF were identified with a mean age of 74.0 ± 10.3 years. Systemic infection (38.4%) was the leading cause for TLE, followed by local infection (37.5%) and lead dysfunction (20.4%). Most of the patients (45.9%) presented with pacemaker systems to be extracted. The total number of leads was 1181 with a 2.3 ± 0.96 leads/patient. Clinical procedural success was achieved in 97.1%. Occurrence of major complications was 1.8% with a procedure-related mortality of 1.0%. All-cause mortality was high with 5.9% and septic shock being the most common cause. Systemic device infection (OR: 49.73; 95% CI: 6.56–377.09, p 〈 0.001), chronic kidney disease (CKD; OR: 2.67; 95% CI: 1.01–7.03, p = 0.048) and a body mass index 〈 21 kg/m2 (OR: 6.6; 95% CI: 1.68–25.87, p = 0.007) were identified as independent predictors for all-cause mortality. Conclusions: TLE in AF patients is effective and safe, but in patients with systemic infection the mortality due to septic shock is high. Systemic infection, CKD and body mass index 〈 21 kg/m2 are risk factors for death in patient with AF undergoing TLE.
    Type of Medium: Online Resource
    ISSN: 1648-9144
    URL: Article
    DOI: 10.3390/medicina58111685
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2088820-X
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  • 5
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    Safety and Efficacy of Excimer Laser Powered Lead Extractions in Obese Patients: A GALLERY Subgroup Analysis
    MDPI AG ; 2023
    In:  Journal of Clinical Medicine Vol. 12, No. 12 ( 2023-06-16), p. 4096-
    Details
    In: Journal of Clinical Medicine, MDPI AG, Vol. 12, No. 12 ( 2023-06-16), p. 4096-
    Abstract: Background: The incidence of cardiac implantable electronic device (CIED)-related complications, as well as the prevalence of obesity, is rising worldwide. Transvenous laser lead extraction (LLE) has grown into a crucial therapeutic option for patients with CIED-related complications but the impact of obesity on LLE is not well understood. Methods and Results: All patients (n = 2524) from the GermAn Laser Lead Extraction RegistrY (GALLERY) were stratified into five groups according to their body mass index (BMI, 〈 18.5; 18.5–24.9; 25–29.9; 30–34.9; ≥35 kg/m2). Patients with a BMI ≥ 35.0 kg/m2 had the highest prevalence of arterial hypertension (84.2%, p 〈 0.001), chronic kidney disease (36.8%, p = 0.020) and diabetes mellitus (51.1%, p 〈 0.001). The rates for procedural minor (p = 0.684) and major complications (p = 0.498), as well as procedural success (p = 0.437), procedure-related (p = 0.533) and all-cause mortality (p = 0.333) were not different between groups. In obese patients (BMI ≥ 30 kg/m2), lead age ≥10 years was identified as a predictor of procedural failure (OR: 2.99; 95% CI: 1.06–8.45; p = 0.038). Lead age ≥10 years (OR: 3.25; 95% CI: 1,31–8.10; p = 0.011) and abandoned leads (OR: 3.08; 95% CI: 1.03–9.22; p = 0.044) were predictors of procedural complications, while patient age ≥75 years seemed protective (OR: 0.27; 95% CI: 0.08–0.93; p = 0.039). Systemic infection was the only predictor for all-cause mortality (OR: 17.68; 95% CI: 4.03–77.49; p 〈 0.001). Conclusions: LLE in obese patients is as safe and effective as in other weight classes, if performed in experienced high-volume centers. Systemic infection remains the main cause of in-hospital mortality in obese patients.
    Type of Medium: Online Resource
    ISSN: 2077-0383
    URL: Article
    DOI: 10.3390/jcm12124096
    Language: English
    Publisher: MDPI AG
    Publication Date: 2023
    detail.hit.zdb_id: 2662592-1
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  • 6
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    High Androgen Receptor mRNA Expression Is Associated with Improved Outcome in Patients with High-Risk Non-Muscle-Invasive Bladder Cancer
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 7 ( 2021-06-30), p. 642-
    Details
    In: Life, MDPI AG, Vol. 11, No. 7 ( 2021-06-30), p. 642-
    Abstract: The role of the androgen receptor (AR) in non-muscle-invasive bladder cancer (NMIBC) remains controversial. We retrospectively analyzed the mRNA expression of AR using RT-qPCR in 95 patients with high-risk NMIBC treated with a bladder-sparing approach and correlated AR with clinical data and recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). The mRNA expression of AR and KRT5, i.e., the basal-like subtype, was strongly correlated (rs = 0.456; p 〈 0.001). AR (p = 0.053) and KRT5 (p = 0.029) mRNA expression was negatively correlated with tumor grade. Kaplan–Meier analyses indicated significantly prolonged CSS (p = 0.020) and OS (p = 0.015) and a trend towards longer RFS (p = 0.051) in patients with high AR expression. High KRT5 expression was associated with significantly longer RFS (p = 0.033), CSS (p = 0.029) and OS (p = 0.030), while high KRT20 expression was associated with reduced RFS (p = 0.042). In multivariable analysis, none of the molecular markers was an independent prognostic factor. When performing a substratification with regard to molecular markers and clinicopathological parameters, high AR expression showed improved OS in patients with high KRT20 mRNA expression (p = 0.041). Women showed significantly longer OS in cases with high AR expression (p = 0.011). High AR was associated with significantly improved CSS in males (p = 0.044) and patients with instillation therapy (p = 0.040), while OS was improved regardless of instillation therapy. Younger patients with high AR expression had significantly improved RFS (p = 0.021), CSS (p = 0.014) and OS (p = 0.007). RFS was also improved in patients with high AR and low expression of either KRT5 (p = 0.003) or KRT20 (p = 0.014), but not in patients with high expression of KRT5 or KRT20. In conclusion, high AR mRNA expression is correlated with KRT5 mRNA expression and is associated with an improved outcome in high-risk NMIBC.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11070642
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 7
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    When SUV Matters: FDG PET/CT at Baseline Correlates with Survival in Soft Tissue and Ewing Sarcoma
    MDPI AG ; 2021
    In:  Life Vol. 11, No. 9 ( 2021-08-24), p. 869-
    Details
    In: Life, MDPI AG, Vol. 11, No. 9 ( 2021-08-24), p. 869-
    Abstract: Introduction: The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas. Materials and Methods: In this retrospective cohort study, we screened over 52′000 PET/CT scans to identify patients diagnosed with either soft tissue, bone or Ewing sarcoma and had a staging scan at our institution before initial therapy. We used a Wilcoxon signed-rank to assess which PET/CT metric was associated with survival in different patient subgroups. Receiver-Operating-Characteristic curve analysis was used to calculate cutoff values. Results: We identified a total of 88 patients with soft tissue (51), bone (26) or Ewing (11) sarcoma. Median age at presentation was 40 years (Range: 9–86 years). High SUVmax was most significantly associated with short survival (defined as 〈 24 months) in soft tissue sarcoma (with a median and range of SUVmax 12.5 (8.8–16.0) in short (n = 18) and 5.5 (3.3–7.2) in long survival (≥24 months) (n = 31), with (p = 0.001). Similar results were seen in Ewing sarcoma (with a median and range of SUVmax 12.1 (7.6–14.7) in short (n = 6) and 3.7 (3.5–5.5) in long survival (n = 5), with (p = 0.017). However, no PET-specific metric but tumor-volume was significantly associated (p = 0.035) with survival in primary bone sarcomas (with a median and range of 217 cm3 (186–349) in short survival (n = 4) and 60 cm3 (22–104) in long survival (n = 19), with (p = 0.035). TLG was significantly inversely associated with long survival only in Ewing sarcoma (p = 0.03). Discussion: Our analysis shows that the outcome of soft tissue, bone and Ewing sarcomas is associated with different PET/CT metrics. We could not confirm the previously suggested superiority of volume-based metrics in soft tissue sarcomas, for which we found SUVmax to remain the best prognostic factor. However, bone sarcomas should probably be evaluated with tumor volume rather than FDG PET activity.
    Type of Medium: Online Resource
    ISSN: 2075-1729
    URL: Article
    DOI: 10.3390/life11090869
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2662250-6
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  • 8
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    Online Resource
    Heavy Metals in Biota in Delaware Bay, NJ: Developing a Food Web Approach to Contaminants
    MDPI AG ; 2019
    In:  Toxics Vol. 7, No. 2 ( 2019-06-13), p. 34-
    Details
    In: Toxics, MDPI AG, Vol. 7, No. 2 ( 2019-06-13), p. 34-
    Abstract: Understanding the relationship between heavy metal and selenium levels in biota and their foods is important, but often difficult to determine because animals eat a variety of organisms. Yet such information is critical to managing species populations, ecological integrity, and risk to receptors (including humans) from consumption of certain prey. We examine levels of cadmium, lead, mercury, and selenium in biota from Delaware Bay (New Jersey, USA) to begin construction of a “springtime” food web that focuses on shorebirds. Horseshoe crab (Limulus polyphemus) eggs are one of the key components at the base of the food web, and crab spawning in spring provides a food resource supporting a massive stopover of shorebirds. Fish and other biota also forage on the crab eggs, and a complex food web leads directly to top-level predators such as bluefish (Pomatomus saltatrix) and striped bass (Morone saxatilis), both of which are consumed by egrets, eagles, ospreys (Pandion haliaetus), and humans. Metal levels in tissues were generally similar in algae, invertebrates, and small fish, and these were similar to those in blood of shorebirds (but not feathers). There was a significant direct relationship between the levels of metals in eggs of horseshoe crabs and mean metal levels in the blood of four species of shorebirds. Metal levels in shorebird feathers were higher than those in blood (except for selenium), reflecting sequestration of metals in feathers during their formation. Levels in feathers of laughing gulls (Leucophaeus atricilla) were similar to those in feathers of shorebirds (except for selenium). Selenium bears special mention as levels were significantly higher in the blood of all shorebird species than in other species in the food web, and were similar to levels in their feathers. Levels of metals in bluefish and striped bass were similar or higher than those found in the blood of shorebirds (except for selenium). The mean levels of cadmium, lead, and mercury in the blood and feathers of shorebirds were below any effect levels, but selenium levels in the blood and feathers of shorebirds were higher than the sublethal effect levels for birds. This is a cause for concern, and warrants further examination.
    Type of Medium: Online Resource
    ISSN: 2305-6304
    URL: Article
    DOI: 10.3390/toxics7020034
    Language: English
    Publisher: MDPI AG
    Publication Date: 2019
    detail.hit.zdb_id: 2733883-6
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  • 9
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    Online Resource
    mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants
    MDPI AG ; 2018
    In:  International Journal of Molecular Sciences Vol. 19, No. 11 ( 2018-10-30), p. 3396-
    Details
    In: International Journal of Molecular Sciences, MDPI AG, Vol. 19, No. 11 ( 2018-10-30), p. 3396-
    Abstract: Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS: 5-year DSS for KRT5 high: 58%; 5-year DSS for KRT20 high: 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20+/KRT5−, 5-year DSS 0%, p 〈 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high: 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20+/KRT− tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
    Type of Medium: Online Resource
    ISSN: 1422-0067
    URL: Article
    DOI: 10.3390/ijms19113396
    Language: English
    Publisher: MDPI AG
    Publication Date: 2018
    detail.hit.zdb_id: 2019364-6
    SSG: 12
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  • 10
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    Calcitriol Promotes Differentiation of Glioma Stem-Like Cells and Increases Their Susceptibility to Temozolomide
    MDPI AG ; 2021
    In:  Cancers Vol. 13, No. 14 ( 2021-07-16), p. 3577-
    Details
    In: Cancers, MDPI AG, Vol. 13, No. 14 ( 2021-07-16), p. 3577-
    Abstract: Glioblastoma (GBM) is the most common and most aggressive primary brain tumor, with a very high rate of recurrence and a median survival of 15 months after diagnosis. Abundant evidence suggests that a certain sub-population of cancer cells harbors a stem-like phenotype and is likely responsible for disease recurrence, treatment resistance and potentially even for the infiltrative growth of GBM. GBM incidence has been negatively correlated with the serum levels of 25-hydroxy-vitamin D3, while the low pH within tumors has been shown to promote the expression of the vitamin D3-degrading enzyme 24-hydroxylase, encoded by the CYP24A1 gene. Therefore, we hypothesized that calcitriol can specifically target stem-like glioblastoma cells and induce their differentiation. Here, we show, using in vitro limiting dilution assays, quantitative real-time PCR, quantitative proteomics and ex vivo adult organotypic brain slice transplantation cultures, that therapeutic doses of calcitriol, the hormonally active form of vitamin D3, reduce stemness to varying extents in a panel of investigated GSC lines, and that it effectively hinders tumor growth of responding GSCs ex vivo. We further show that calcitriol synergizes with Temozolomide ex vivo to completely eliminate some GSC tumors. These findings indicate that calcitriol carries potential as an adjuvant therapy for a subgroup of GBM patients and should be analyzed in more detail in follow-up studies.
    Type of Medium: Online Resource
    ISSN: 2072-6694
    URL: Article
    DOI: 10.3390/cancers13143577
    Language: English
    Publisher: MDPI AG
    Publication Date: 2021
    detail.hit.zdb_id: 2527080-1
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