Transrectal ultrasound for intraoperative interstitial needle guidance in cervical cancer brachytherapy.

OBJECTIVE: This study aimed to prospectively assess the visibility of interstitial needles on transrectal ultrasound (TRUS) in cervical cancer brachytherapy patients and evaluate its impact on implant and treatment plan quality. MATERIAL AND METHODS: TRUS was utilized during and after applicator insertion, with each needle's visibility documented through axial images at the high-risk clinical target volume's largest diameter. Needle visibility on TRUS was scored from 0 (no visibility) to 3 (excellent discrimination, margins distinct). Quantitative assessment involved measuring the distance between tandem and each needle on TRUS and comparing it to respective magnetic resonance imaging (MRI) measurements. Expected treatment plan quality based on TRUS images was rated from 1 (meeting all planning objectives) to 4 (violation of High-risk clinical target volume (CTVHR) and/or organ at risk (OAR) hard constraints) and compared to the final MRI-based plan. RESULTS: Analysis included 23 patients with local FIGO stage IB2-IVA, comprising 41 applications with a total of 230 needles. A high visibility rate of 99.1% (228/230 needles) was observed, with a mean visibility score of 2.5 ±â€¯0.7 for visible needles. The maximum and mean difference between MRI and TRUS measurements were 8 mm and -0.1 ±â€¯1.6 mm, respectively, with > 3 mm discrepancies in 3.5% of needles. Expected treatment plan quality after TRUS assessment exactly aligned with the final MRI plan in 28 out of 41 applications with only minor deviations in all other cases. CONCLUSION: Real-time TRUS-guided interstitial needle placement yielded high-quality implants, thanks to excellent needle visibility during insertion. This supports the potential of TRUS-guided brachytherapy as a promising modality for gynecological indications.

High fibrinogen levels are associated with poor survival in patients with liposarcoma.

The aim of this study was to evaluate whether (preoperative) plasma levels of fibrinogen, an essential clotting and acute phase protein, are associated with the prognosis of patients with a liposarcoma, a subtype of sarcoma derived from adipose tissue. We performed a retrospective cohort study of 158 patients with liposarcoma treated at the Department of Orthopaedics of the Medical University of Vienna in Austria from May 1994 to October 2021. Kaplan-Meier curves as well as uni- and multivariable Cox proportional hazard models were performed to evaluate the association between fibrinogen levels and overall survival. Elevated fibrinogen was associated with adverse overall survival in cause specific hazards analysis of mortality (hazard ratio [HR] per 10 mg/dL increase: 1.04; 95% CI 1.02-1.06; p < 0.001). This association prevailed in multivariable analysis after adjustment for AJCC tumor stage (HR 1.03; 95% CI 1.01-1.05; p = 0.013). Increasing levels of fibrinogen, a routinely available and inexpensive parameter, predicts the risk of mortality in patients with liposarcoma.

Litigations in orthopedics and trauma surgery: reasons, dynamics, and profiles.

BACKGROUND: In recent literature, the increasing number of medical litigations, both in terms of the number of cases being filed and the substantive costs associated with lawsuits, has been described. This study aims to provide an overview of the profile of litigation for orthopedic and trauma surgery to describe the differences and the development of the number of cases over time. PATIENTS AND MATERIALS: A retrospective review of all litigations between 2000 and 2017 was conducted using the institutional legal database. The causes of litigation were documented and classified into seven major categories. In addition to plaintiff characteristics, the litigation outcomes and the differences between emergency and elective surgery were analyzed. RESULTS: A total of 230 cases were evaluated. The mean age of the plaintiffs was 44.6 ± 20.1 years, and 56.8% were female. The main reasons for litigation were claimed inappropriate management (46.1%), misdiagnosis (22.6), and poor nursing care (8.3%). Significantly more litigations were filed against surgeons of the orthopedic subspecialty compared with trauma surgeons (78%; p ≤ 0.0001). There were significantly fewer litigations per 1000 cases filed overall in 2009-2017 (65% less; p = 0.003) than in 2000-2008. CONCLUSION: Our results could not confirm the often-stated trend of having more litigations against orthopedic and trauma surgeons. Although the absolute numbers increased, the number of litigations per 1000 patients treated declined. Patients who underwent elective surgery were more likely to file complaints than emergency patients.

Primary melanoma of the bladder: a case report and review of the literature.

OBJECTIVE: Primary bladder melanomas are rare and aggressive neoplasms. We herein described a new case and performed a review of the literature. PATIENTS AND METHODS: We present the case of a 81-year-old woman with a primary mucosal melanoma of the bladder after a history of acral melanoma (KRAS mutated) and lentigo maligna of the forehead. Using PubMed, we found that in literature 38 cases were described. RESULTS: In our patients, during a transurethral resection (TURBT), two bladder lesions were detected. The histologic exam revealed a malignant melanoma, Mib1/ki67: 10-12%, PDL1 <1%. No BRAF, NRAS or KRAS mutations were detected. She subsequently underwent a transurethral revision of the trigone and a partial cystectomy of the dome with bilateral pelvic lymph node dissection. Microscopical findings showed a residual 5 mm non-muscle-invasive melanoma of the bladder, with negativity of the surgical margins and of the 17 pelvic lymph nodes. No adjuvant treatment was proposed. To date the patient is disease-free. CONCLUSIONS: Primary bladder melanoma carries a poor prognosis and poses a therapeutic challenge to clinicians who manage patients with this rare condition. In our experience the multidisciplinary approach for the diagnosis and management of this rare cancer is mandatory.

Changes in Circulating Stem and Progenitor Cell Numbers Following Acute Exercise in Healthy Human Subjects: a Systematic Review and Meta-analysis.

Despite of the increasing number of investigations on the effects of acute exercise on circulating stem and progenitor cell (SC) numbers, and in particular on respective subgroups, i.e. endothelial (ESC), hematopoietic (HSC), and mesenchymal (MSC) stem and progenitor cells, a consensus regarding mechanisms and extent of these effects is still missing. The aim of this meta-analysis was to systematically evaluate the overall-effects of acute exercise on the different SC-subgroups and investigate possible subject- and intervention-dependent factors affecting the extent of SC-mobilization in healthy humans. Trials assessing SC numbers before and at least one timepoint after acute exercise, were identified in a systematic computerized search. Compared to baseline, numbers were significantly increased for early and non-specified SCs (enSCs) until up to 0.5 h after exercise (0-5 min: +0.64 [Standardized difference in means], p < 0.001; 6-20 min: +0.42, p < 0.001; 0.5 h: +0.29, p = 0.049), for ESCs until 12-48 h after exercise (0-5 min: +0.66, p < 0.001; 6-20 min: +0.43 p < 0.001; 0.5 h: +0.43, p = 0.002; 1 h: +0.58, p = 0.001; 2 h: +0.50, p = 0.002; 3-8 h: +0.70, p < 0.001; 12-48 h: +0.38, p = 0.003) and for HSCs at 0-5 min (+ 0.47, p < 0.001) and at 3 h after exercise (+ 0.68, p < 0.001). Sex, intensity and duration of the intervention had generally no influence. The extent and kinetics of the exercise-induced mobilization of SCs differ between SC-subpopulations. However, also definitions of SC-subpopulations are non-uniform. Therefore, finding a consensus with a clear definition of cell surface markers defining ESCs, HSCs and MSCs is a first prerequisite for understanding this important topic.

Genotype-by-environment interactions at the trait level and total merit index level for milk production and functional traits in Brown Swiss cattle.

The production environments of the German-Austrian Brown Swiss population show a wide range due to differences in topography, landscapes, local climates, and different farm management systems. Extensive production systems such as organic farming have become increasingly popular in recent decades because of interest in sustainability and consumer preferences. Compared with conventional farmers, organic farmers put more weight on fitness traits. Besides the official total merit index (TMI), a selection index applying relative economic weights (REWs) suitable for organic production systems is provided for Brown Swiss cattle in Germany. The aim of the study was to investigate genotype-by-environment interactions (GxE) for milk production traits and functional traits (including longevity, fertility traits, and calving traits) in a sample of the German-Austrian Brown Swiss population housed in Baden-Wuerttemberg (southern Germany) by applying bivariate and random regression sire models. For bivariate analyses, the production environment was binary classified by farm management system (organic and conventional) and altitude of farm location (above or below 800 m above sea level (ASL)). Milk energy yields (MEY) obtained from herd effects were used as continuously scaled environmental descriptor in the reaction norm approach. The TMIs for sires were calculated based on breeding values estimated with different models and environment-specific REWs to determine possible GxE at TMI levels and rerankings of sires. In bivariate analyses, genetic correlations at the trait level were high and ranged from rg = 0.99 (calving to first insemination, cystic ovaries, and maternal stillbirth rate) to rg = 0.79 (first insemination to conception for altitude). Except for the latter, no severe GxE were found at the trait level using the bivariate models. Fat yield was the only trait showing minor GxE in the reaction norm model approach. Investigating the environmental sensitivity at the TMI level revealed rank correlations between the different environment-specific TMIs that were close to unity, implying no severe reranking effects. The results show no need to account for different environments in Brown Swiss cattle breeding programs.

El ojo: Un rompecabezas diagnóstico: Estudio observacional descriptivo y revisión / The Eye: A Diagnostic Puzzle: Descriptive observational study and review

Se comunica una serie de casos, multicéntricos de la cual participaron cinco instituciones. La muestra fue de 17 pacientes, de los cuales 11 pertenecían al Hospital Dr. J.M. Cullen. Todos consultaron por compromiso orbitario y/o periorbitario. El compromiso en hombres fue de 23.4% y un 76.6% en mujeres. La edad media en años fue de 45.4 (17-69 años). Dentro de los diagnósticos encontrados, cinco casos fueron Enfermedad Relacionada con IgG4 (ER-IgG4), dos casos de Enfermedad de Erdheim Chester (EEC), dos Xantogranuloma, dos xantelasmas, un caso de metástasis de cáncer de mama, un caso de orbitopatía tiroidea, un caso de Amiloidosis con mieloma múltiple, y tres sin diagnóstico. Se revisan los diagnósticos diferenciales encontrados.

A series of multicentric cases is reported, of which five institutions participated. The sample was of 17 patients, of which 11 belonged to our Hospital, the Dr. J.M. Cullen Hospital. All consulted for orbital and/or periorbital commitment. The commitment in men was 23.4% and 76.6% in women. The average age in years was 45.4 (17-69 years). Among the diagnoses found, five cases were IgG4-Related Disease, two cases of Erdheim Chester Disease, two Xantogranuloma, two xanthelasmas, a case of breast cancer metastases, a case of thyroid orbitopathy, a case of Amyloidosis with multiple myeloma, and three without diagnosis. Differential diagnoses found are reviewed.

[Lung ultrasonography in COVID-19 pneumonia]. / Sonographische Bildgebung der Lunge bei COVID-19.

BACKGROUND: Point-of-care ultrasound (POCUS) of the lung in patients with COVID-19 plays a key role in the emergency room and intensive care unit. Lung ultrasound is able to depict typical pulmonary findings of COVID-19 and is therefore suitable for diagnosis and follow-up of these patients. CLINICAL/METHODOLOGICAL ISSUE: Lung ultrasound in COVID-19 patients in the emergency room and intensive care unit. STANDARD RADIOLOGICAL METHODS: Computed tomography (low-dose CT) and X­ray of the lung. METHODOLOGICAL INNOVATIONS: Lung ultrasound in COVID-19 patients. RECOMMENDATIONS: Lung ultrasound in patients with COVID-19 offers similar performance as CT and is superior when compared to X­ray in evaluating pneumonia and acute respiratory distress syndrome (ARDS). Lung ultrasound plays an important role in the emergency room and intensive care unit. POCUS reduces exposure to radiation, therapy delays, and minimizes transport of high-risk patients. Differential diagnoses can also be clarified.

Clinical and imaging findings in cervical cancer and their impact on FIGO and TNM staging - An analysis from the EMBRACE study.

OBJECTIVE: To investigate differences in local tumour staging between clinical examination and MRI and differences between FIGO 2009, FIGO 2018 and TNM in patients with primary cervical cancer undergoing definitive radio-chemotherapy. METHODS: Patients from the prospective observational multi-centre study "EMBRACE" were considered for analysis. All patients had gynaecological examination and pelvic MRI before treatment. Nodal status was assessed by MRI, CT, PET-CT or lymphadenectomy. For this analysis, patients were restaged according to the FIGO 2009, FIGO 2018 and TNM staging system. The local tumour stage was evaluated for MRI and clinical examination separately. Descriptive statistics were used to compare local tumour stages and different staging systems. RESULTS: Data was available from 1338 patients. For local tumour staging, differences between MRI and clinical examination were found in 364 patients (27.2%). Affected lymph nodes were detected in 52%. The two most frequent stages with FIGO 2009 are IIB (54%) and IIIB (16%), with FIGO 2018 IIIC1 (43%) and IIB (27%) and with TNM T2b N0 M0 (27%) and T2b N1 M0 (23%) in this cohort. CONCLUSIONS: MRI and clinical examination resulted in a different local tumour staging in approximately one quarter of patients. Comprehensive knowledge of the differential value of clinical examination and MRI is necessary to define one final local stage, especially when a decision about treatment options is to be taken. The use of FIGO 2009, FIGO 2018 and TNM staging system leads to differences in stage distributions complicating comparability of treatment results. TNM provides the most differentiated stage allocation.

Prevalence of somatic and psychiatric morbidity across occupations in Switzerland and its correlation with suicide mortality: results from the Swiss National Cohort (1990-2014).

BACKGROUND: Suicide is a major and complex public health problem. In Switzerland, suicide accounts for about 1000 deaths yearly and is the fourth leading cause of mortality. The first nationwide Swiss study of suicides identified eight male and four female occupations with statistically significant excess of suicide compared to the general Swiss population. Working time, self-employer status, low socio-economic status and low skill level required for occupation were associated with increase in suicide risk. Presently, we aim to compare the distribution of suicide risk across occupations with the prevalence of somatic and psychiatric morbidity in Swiss working-aged adults. We hypothesized that some diseases would cluster in particular occupations, indicating potential work-relatedness of suicides found in these occupations. METHODS: We used the Swiss National Cohort (SNC) and included 10575 males and 2756 females deceased by suicide between 1990 and 2014. We estimated the prevalence of 16 categories of concomitant diseases in each occupation, using national mortality records, and assessed the homogeneity of diseases distribution across occupations. For diseases, which prevalence varied significantly across occupations, we analyzed the correlation with the distribution of suicide risk, estimated as the standardized mortality ratio (SMR) of suicide. RESULTS: Mental and behavioral disorders were the most commonly reported concomitant diseases in our population. In men, the prevalence of these disorders and more specifically, the prevalence of substance-related and addictive disorders, and of psychotic disorders varied significantly across occupations and was correlated with the SMR of suicide. The prevalence of malignant neoplasms and the prevalence of diseases of the musculoskeletal system and connective tissue also varied significantly across male occupations, while in women, such a variation was observed for neoplasms of uncertain or unknown behavior and diseases of the nervous system and sense organs, without being correlated with the SMR of suicide. CONCLUSION: Some of the identified morbidities can be occupation-related and could negatively affect the working capacity and the employability, which in turn could be related to the suicide. Disentangling concomitant diseases according to their work-relatedness and relationship with the suicide risk is important for identifying occupation-related suicides, understanding their characteristics, and developing appropriated interventions for their prevention.

Unravelling Receptor and RGD Motif Dependence of Retargeted Adenoviral Vectors using Advanced Tumor Model Systems.

Recent advances in engineering adenoviruses are paving the way for new therapeutic gene delivery approaches in cancer. However, there is limited knowledge regarding the impact of adenoviral retargeting on transduction efficiency in more complex tumor architectures, and the role of the RGD loop at the penton base in retargeting is unclear. To address this gap, we used tumor models of increasing complexity to study the role of the receptor and the RGD motif. Employing tumor-fibroblast co-culture models, we demonstrate the importance of the RGD motif for efficient transduction in 2D through the epithelial cell adhesion molecule (EpCAM), but not the epidermal growth factor receptor (EGFR). Via optical clearing of co-culture spheroids, we show that the RGD motif is required for transduction via both receptors in 3D tumor architectures. We subsequently employed a custom-designed microfluidic model containing collagen-embedded tumor spheroids, mimicking the interplay between interstitial flow, extracellular matrix and adenoviral transduction. Image analysis of on-chip cleared spheroids indicated the importance of the RGD motif for on-chip adenoviral transduction. Together, our results show the interrelationship between receptor characteristics, the RGD motif, the 3D tumor architecture and retargeted adenoviral transduction efficiency. The findings are important for the rational design of next-generation therapeutic adenoviruses.

Common surgical procedures in pilonidal sinus disease: A meta-analysis, merged data analysis, and comprehensive study on recurrence.

We systematically searched available databases. We reviewed 6,143 studies published from 1833 to 2017. Reports in English, French, German, Italian, and Spanish were considered, as were publications in other languages if definitive treatment and recurrence at specific follow-up times were described in an English abstract. We assessed data in the manner of a meta-analysis of RCTs; further we assessed non-RCTs in the manner of a merged data analysis. In the RCT analysis including 11,730 patients, Limberg & Dufourmentel operations were associated with low recurrence of 0.6% (95%CI 0.3-0.9%) 12 months and 1.8% (95%CI 1.1-2.4%) respectively 24 months postoperatively. Analysing 89,583 patients from RCTs and non-RCTs, the Karydakis & Bascom approaches were associated with recurrence of only 0.2% (95%CI 0.1-0.3%) 12 months and 0.6% (95%CI 0.5-0.8%) 24 months postoperatively. Primary midline closure exhibited long-term recurrence up to 67.9% (95%CI 53.3-82.4%) 240 months post-surgery. For most procedures, only a few RCTs without long term follow up data exist, but substitute data from numerous non-RCTs are available. Recurrence in PSD is highly dependent on surgical procedure and by follow-up time; both must be considered when drawing conclusions regarding the efficacy of a procedure.

First-trimester risk assessment based on ultrasound and cell-free DNA vs combined screening: a randomized controlled trial.

OBJECTIVE: This was a randomized controlled trial to compare risk assessment by first-trimester combined screening (FTCS) with an approach that combines a detailed ultrasound examination at 11-13 weeks' gestation and cell-free DNA (cfDNA) analysis. METHODS: Pregnant women with a normal first-trimester ultrasound examination at 11-13 weeks' gestation (fetal nuchal translucency (NT) ≤ 3.5 mm and no fetal defects) were randomized into one of two groups. In the first group, risk of aneuploidy was assessed using FTCS based on the most recent UK Fetal Medicine Foundation algorithm. In the second group, risk assessment was based on ultrasound findings and cfDNA analysis. An additional tube of blood was collected for FTCS in case the cfDNA analysis was uninformative. Primary outcome was false-positive rate in screening for trisomy 21. A case was considered false positive if the karyotype was not trisomy 21 and if the risk for trisomy 21 was >1:100, irrespective of the method of risk calculation. Results were compared using 95% CIs using the Clopper-Pearson method. RESULTS: Between October 2015 and December 2016, 1518 women with singleton pregnancy underwent first-trimester screening. Thirty-one (2.0%) pregnancies were not eligible for randomization due to increased NT (> 3.5 mm) and/or fetal defect. After exclusion of women who declined randomization (n = 87) and cases of fetal death and loss to follow-up (n = 24), 688 pregnancies were randomized into the FTCS arm and 688 into the ultrasound + cfDNA analysis arm. There were no differences in maternal and gestational age, maternal weight and BMI, ethnicity, use of assisted reproduction and cigarette smoking between the two arms. In the ultrasound + cfDNA analysis arm, median risk for trisomy 21 was 1 in 10 000. None of the cases had a risk above 1: 100 (95% CI, 0.0-0.5%). In the FTCS arm, the median risk for trisomy 21 was 1 in 3787 and in 17 cases, the risk was higher than 1:100, which corresponds to 2.5% (95% CI, 1.5-3.9%) of the FTCS study-arm population. CONCLUSION: Our study has shown that first-trimester risk assessment for trisomy 21 that includes a detailed ultrasound examination as well as NT measurement and is followed by cfDNA testing is associated with a significant reduction in the false-positive rate compared with FTCS. This approach obviates the need for maternal serum free ß-human chorionic gonadotropin and pregnancy-associated plasma protein-A in screening for fetal aneuploidy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of Focal Laser Treatment Based on External Imaging (OCT) Using a Navigated Retinal Laser System - a Case Series.

Background The navigated laser photocoagulation system (NAVILAS®, OD-OS GmBH, Teltow, Germany) is a laser treatment device that provides navigated laser treatment of the retina based on a fundus image. The purpose of this study was to investigate the accuracy of laser treatment based on external optical coherence tomography (OCT) images - a new application of the device. Patients and Methods This retrospective case series evaluated the accuracy of laser spot placement in 7 eyes after using overlaid external OCT images for planning NAVILAS laser treatment. After a mean time of 33 days, a post-treatment OCT was obtained and compared with the pretreatment plan on the previous OCT. Laser spots touching or overlapping the planned 100 µm laser spots were classified as "match" and invisible laser spots as "laser spot not evolved". Results A total of 477 laser spots in 7 eyes were evaluated (mean: 68 spots per eye). Of all planned laser spots, 361 (75.7 %) were visible on post-treatment OCT. 58.7 % of these spots matched the pretreatment plan. Non-matching laser spots showed no uniform pattern of dislocation. Conclusions Planning navigated NAVILAS Laser treatment based on manually imported OCT images seems to be less accurate than planning with NAVILAS integrated imaging. These findings warrant further evaluation, not only regarding the recently installed automated picture importing tool but also concerning its clinical impact, which is possibly outweighed by the advantages of the additional image information.

Inflammation, vitamin D and dendritic cell precursors in chronic kidney disease.

Decreased blood dendritic cell precursors (DCP) count is linked with atherosclerotic disease, while reduction of circulating DCP is also seen in patients with chronic kidney disease (CKD). As poor vitamin D status could be linked to a compromised innate immune response, we hypothesized that vitamin D status might be involved in the decrease in circulating DCP in CKD. Moreover, the potential role of inflammation was considered. Circulating myeloid (mDCP), plasmacytoid (pDCP) and total DCP (tDCP) were analysed using flow cytometry in 287 patients with CKD stage 3. Serum 25(OH)D and 1,25(OH)2D levels were measured using enzyme-linked immunosorbent assays (ELISA), interleukin (IL)-6, IL-10 and tumour necrosis factor (TNF)-α using cytometric bead array, C-reactive protein (CRP) using a high-sensitivity (hs) ELISA. Contrary to our hypothesis, there was no association between vitamin D levels and DCP, although their number was decreased significantly in CKD (P < 0·001). Instead, mDCP (r = -0·211) and tDCP (r = -0·188,) were associated slightly negatively with hsCRP but positively with the estimated glomerular filtration rate (eGFR, r = 0·314 for tDCP). According to multivariate linear regression, only higher hsCRP concentration and the presence of diabetes mellitus had a significant negative influence on DCP count (P < 0·03, respectively) but not vitamin D, age and eGFR. A significant impact of vitamin D on the reduction of circulating DCP in CKD 3 patients can be neglected. Instead, inflammation as a common phenomenon in CKD and diabetes mellitus had the main influence on the decrease in DCP. Thus, a potential role for DCP as a sensitive marker of inflammation and cardiovascular risk should be elucidated in future studies.

Critical analysis of a simplified Fuhrman grading scheme for prediction of cancer specific mortality in patients with clear cell renal cell carcinoma--Impact on prognosis.

INTRODUCTION AND OBJECTIVES: The traditional 4-tiered Fuhrman grading system (FGS) is widely accepted as histopathological classification for clear cell renal cell carcinoma (ccRCC) and has shown prognostic value. As intra- and inter-observer agreement are sub-optimal, simplified 2- or 3-tiered FGSs have been proposed. We aimed to validate these simplified 2- or 3-tiered FGSs for prediction of cancer-specific mortality (CSM) in a large study population from 2 European tertiary care centers. METHODS: We identified and followed-up 2415 patients with ccRCC who underwent radical or partial nephrectomy in 2 European tertiary care centers. Univariable and multivariable analyses and prognostic accuracy analyses were performed to evaluate the ability of several simplified FGSs (i.e. grades I + II vs., grades III + IV, grades I + II vs. grade III and grade IV) to predict CSM. RESULTS: Independent predictor status in multivariate analyses was proved for the simplified 2-tiered FGS (high-grade vs. low-grade), for the simplified 3-tiered FGS (grades I + II vs. grade III and grade IV) as well as for the traditional 4-tiered FGS. The prognostic accuracy of multivariable models of 77% was identical for all tested models. Prognostic accuracy of the model without FG was 75%. CONCLUSIONS: A simplified 2- or 3-tiered FGS could predict CSM as accurate as the traditional 4-tiered FGS in a large European study population. Application of new simplified 2- or 3-tiered FGS may reduce inter-observer-variability and facilitate clinical practice without compromising the ability to predict CSM in ccRCC patients after radical or partial nephrectomy.

[Complications of Descemet Stripping Automated Endothelial Keratoplasty (DSAEK)]. / Komplikationen der Descemet Stripping Automatisierten Endothelkeratoplastik (DSAEK).

BACKGROUND: Lamellar keratoplasties, e.g. Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) are considered the procedures of choice for corneal endothelial diseases. In comparison to penetrating keratoplasty (PK) they are associated with faster visual rehabilitation, a lower risk of complications and a decreased necessity for follow-up visits, which reduces the burden on quality of life in elderly patients. In order to advise patients regarding the indications for surgery and to facilitate the follow-up management, it is important to know the most important complications associated with these keratoplasty techniques. RESULTS AND DISCUSSION: The most important preoperative complication is a delayed indication for the operation. In contrast to PK, DSAEK and DMEK surgery should be provided at an earlier stage of disease as chronic edema alters the stroma and reduces the speed of visual recovery. The most important complications during or early after surgery are detached lamellae, pupillary blocks with increased pressure or air bubbles in the vitreous cavity in patients with previous vitrectomy. The main long-term complications include chronic increased intraocular pressure and immune-mediated graft rejections in DSAEK patients after reducing or stopping topical corticosteroid therapy. This article describes the potential complications of endothelial keratoplasty and provides a detailed explanation of strategies to avoid these complications.

Medical androgen deprivation therapy and increased non-cancer mortality in non-metastatic prostate cancer patients aged ≥66 years.

PURPOSE: To examine the potential relationship between androgen deprivation therapy and other-cause mortality (OCM) in patients with prostate cancer treated with medical primary-androgen deprivation therapy, prostatectomy, or radiation. METHODS: A total of 137,524 patients with non-metastatic PCa treated between 1995 and 2009 within the Surveillance Epidemiology and End Results Medicare-linked database were included. Cox-regression analysis tested the association of ADT with OCM. A 40-item comorbidity score was used for adjustment. RESULTS: Overall, 9.3% of patients harbored stage III-IV disease, and 57.7% of patients received ADT. The mean duration of ADT exposure was 22.9 months (median: 9.1; IQR: 2.8-31.5). Mean and median follow-up were 66.9, and 60.4 months, respectively. At 10 years, overall-OCM rate was 36.5%; it was 30.6% in patients treated without ADT vs. 40.1% in patients treated with ADT (p < 0.001). In multivariable-analysis, ADT was associated with an increased risk of OCM (Hazard-ratio [HR]: 1.11, 95% Confidence-interval [95% CI]: 1.08-1.13). Patients with no comorbidity (10-year OCM excess risk: 9%) were more subject to harm from ADT than patients with high comorbidity (10-year OCM excess risk: 4.7%). CONCLUSIONS: In patients with PCa, treatment with medical ADT may increase the risk of mortality due to causes other than PCa. Whether this is a simple association or a cause-effect relationship is unknown and warrants further study in prospective studies.

In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells.

Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi- or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS(61K) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.