The influence of obesity, diabetes mellitus and smoking on fuchs endothelial corneal dystrophy (FECD).

To detect environmental factors, which may be possible risk factors in the disease course of Fuchs' endothelial corneal dystrophy (FECD). Evaluation of patients with FECD registered in the FECD genetics database of the Center for Ophthalmology, University Hospital Cologne. For the evaluation, disease onset, central corneal thickness, best spectacle corrected visual acuity (BSCVA, logMAR), and modified Krachmer grading (grades 1-6) were correlated with the presence of diabetes mellitus (DM), body mass index (BMI), and smoking behavior. To put the age-related increase in Krachmer grading into perspective, a correction of grading were formed. Depending on the variables studied, differences between groups were examined by Mann-Whitney U test and chi-square test. The significance level was 5%. 403 patients with FECD were included in the analysis. The mean age of the patients was 70.0 ± 10.32 (range 28-96) years. The mean age at diagnosis of those patients was 63.1 ± 13.2 years. The female-to-male ratio was 1.46:1. Patients with a BMI > 30.0 kg/m2 developed FECD significantly earlier than patients with a BMI < 30 kg/m2, p = 0.001. Patients with DM showed significantly more often an Krachmer grade of 5, p = 0.015. Smoking had a negative effect on Krachmer grading (p = 0.024). Using the mediation analysis, the presence of DM correlated Krachmer Grade 5 (p = 0.015), and the presence of DM correlated with BMI > 30.0 kg/m2 (p = 0.012). In addition to smoking and DM our study shows for the first time that obesity may have a negative impact on the development of FECD. Whether dietary interventions and hormones can influence the development or progression of the disease needs to be investigated in future studies.

First assessment of flow phenomena of acute and chronic thrombosis in the jugular veins using new ultrasound vector-flow imaging.

AIM: First assessment of flow changes in the jugular veins using high resolution ultrasound vector flow. MATERIAL UND METHODS: 15 patients (8 males, 7 females) with an age range of 35 to 82 years (mean age 58.53±12.26 years) were examined by an experienced examiner using high power ultrasound equipment (Resona R9, Mindray) with probe technology (Mindray L9-3U Linear Array transducer, 2.5 to 9.0 MHz). This group was compared with five healthy subjects (mean age 35.4±13.79 years) as a reference. To assess flow changes, the color-coded duplex sonography and the novel vector flow technique were used. The evaluation was performed of vector morphology changes, turbulence, and wall resistance measurements. RESULTS: There were changes after acute and chronic thrombosis in 9 cases, and venous compression in 7 cases. Turbulence was measurable from 0.01 % to 64.44 %, the average turbulence was 19.73±22.06 %. Wall resistance measurement showed values from 0.01 Pa to 3.14 Pa, depending on the age of the thrombosis or compression. The reference veins showed turbulence of 0.94±1.5 % and a mean wall resistance of 0.05±0.05 Pa. There are statistically significant differences between normal and thrombotic or compressed veins in terms of maximum wall stress (p = 0.006) and mean degree of turbulence (p = 0.012), while the difference in mean wall stress is not statistically significant (p = 0.058). CONCLUSION: Despite still existing technical limitations, the combination of V-flow and wall stress measurements in jugular vein changes suggests a high diagnostic potential.

High resolution flow (HR Flow) and Glazing Flow in cases of hepatic flow changes: Comparison to color-coded Doppler sonography (CCDS).

AIM: To evaluate the possibilities of flow detection using high resolution flow (HR Flow) and Glazing Flow technique in patients with liver parenchymal changes and flow changes in comparison to color-coded Doppler sonography (CCDS). MATERIAL AND METHODS: All examinations were performed using a multi frequency matrix convex probe with high resolution technique (SC6-1U/Resona7, Mindray, Shenzhen, China) by one experienced examiner to evaluate the venous, portal venous and arterial liver flow with digital documentation of the dynamic flow parameters like peak systolic flow, end-diastolic flow and resistance index. For liver parenchymal stiffness changes shear wave elastography was performed with at least 10 measurements. By two independent readers an elevation was performed to evaluate the image quality and the degree of flow artefacts, from 0 = not available to 5 points with excellent image quality without flow artefacts. RESULTS: All 40 patients (24 men, 16 women, age 27-83 years, mean 56±5 years) showed morphology changes from B-Mode of the liver parenchyma to inhomogeneous tissue with higher stiffness evaluated by the shear wave elastography (1.45 m/s up to 2.79 m/s±1.79 m/s, considering F1 up to F4 fibrosis) and in 15 cases histopathologically proven liver cirrhosis. In 9 cases after non-acute thrombosis flow reduction of the portal vein was the reason for the diameter less than 5 mm. Flow parameters for the venous flow were between 8 cm/s up to 29 cm/s, mean 14±4 cm/s, for the hepatic portal vein 5 cm/s up to 57 cm/s, mean 17±5 cm/s, for the hepatic artery systolic flow between 50 cm/s up to 127±33 cm/s, end-diastolic flow from 22 cm/s up to 47±8 cm/s. Resistance index for the hepatic artery was between 0.41 up to 0.73, mean 0.67±0.25. The image quality for CCDS over all cases was evaluated for CCDS between 1 up to 4. The mean quality was 2.5±0.5, for HR Flow in combination with Glazing Flow 3±0.5, with significant differences for the 2 readers (P < 0.01). CONCLUSION: Combination of HR Flow with Glazing Flow could be helpful to evaluate morphological und hemodynamic changes of liver arterial flow, portal venous and venous flow. Reduction of flow artefacts in combination with a higher image quality could be helpful for optimizing the digital measurements also for follow up examinations.

High-performance sonographical multimodal imaging of non cystic thyroid lesions: Chances of the preoperative diagnostics in relation to histopathology.

AIM: To improve preoperative diagnostics of solid non-cystic thyroid lesions by using new high-performance ultrasound techniques: optimized B-mode morphology, elastography, Color-Coded Doppler-Sonography (CCDS) and contrast enhanced ultrasound (CEUS)MATERIALS AND METHODS:In 33 cases solid, non-cystic thyroid lesions were rated as TIRADS 3 and up from conventional B-mode examinations. Additional high resolution Power Doppler including HR- and Glazing-Flow as optimized macrovascularization techniques, shear wave elastography and CEUS were performed on these patients by one experienced examiner. For CEUS a bolus of 1-2.4 ml Sulfurhexafluorid microbubbles (SonoVue®, Bracco, Milan, Italy) was injected into a cubital vein and then the distribution kinetics of the contrast agent were documented from the early arterial phase (10 to 15 seconds after injection) to the late venous phase (5 minutes after injection). Postoperative histopathology was the diagnostic gold standard as it provides the most reliable proof. RESULTS: 33 patients (13 males, 20 females; age 29 -77 years; mean 55 years; SD 13 years) were included in this study. 28 of them had benign regressive thyroid nodules, 3 had adenomas and 4 were diagnosed with carcinomas (3 were histologically identified as papillary thyroid carcinomas, one as a medullary thyroid carcinoma). The volume of the thyroid gland ranged from 6.6 to 401.3 cm2 (mean 72.6±92.0 cm2).The adenoma diameters ranged from 9 to 40 mm (mean 22±16 mm) and the carcinoma diameters ranged from 19 to 33 mm (mean 26±6 mm). The 3 adenomas had different echogenicities: One was completely echofree, one was hypoechoic and one isoechoic. The 4 carcinomas however were equally characterized as hypoechoic and echofree. Two of three adenomas and all of the carcinomas showed an incomplete or diffuse margin. Micro-calcifications were found in one adenoma and in every carcinoma. However, no micro-calcifications were observed in cases of benign regressive nodules.Performing shear-wave elastography the adenomas showed lower values than the carcinomas: The tissue velocity of the adenomas ranged from 2.86 m/s to 3.85 m/s (mean 3.32±0.5 m/s) and in carcinomas from 3.89 m/s to 5.66 m/s (mean 4.18±0.3 m/s).Marginal hypervascularization was detected in two adenomas after applying CCDS. One adenoma was hypovascularized. The four carcinomas showed an irregular extreme hypervascularization along their margins as well as an irregular central normo- or hypervascularization in CCDS. The additional HR-Flow helped reducing artefacts.In CEUS the dynamic capillary microvascularization of all carcinomas was very irregular with early enhancement and followed by partial or complete wash-out. In CEUS two adenomas had no wash-out and the other one showed a partial wash-out. CONCLUSION: Using modern multimodal imaging offers new possibilities for the differentiation between benign and malignant thyroid lesions. It is a very important diagnostic tool in addition to the B-Mode TIRADS classification and eases the decision between TIRADS 3, 4 and 5. However, additional multicenter studies are required for more detailed evaluations.

Wireless point-of-care ultrasound: First experiences with a new generation handheld device.

AIM: To evaluate the diagnostic reliability of a new generation wireless point-of care ultrasound device for abdominal and thoracic findings. MATERIAL AND METHODS: 40 patients (16 females, 24 males 19 -80 years, on average 56.1 years) were scanned by an experienced examiner using the new wireless Vscan Air device for abdominal and thoracic findings. The probe frequencies were 2-5 MHz (convex probe) and 3-12 MHz for the linear probe. As a reference standard, all patients were also examined using high-end ultrasound (LOGIQ E9/LOGIQ E10). Results were interpreted independently by two examiners in consensus, also with regard to the image quality (0-4, from not assessable = 0, to excellent 4). RESULTS: In all 40 patients (100%) examination with conventional high-end ultrasound and the Vscan Air ultrasound device was feasible. Sensitivity, specificity, positive and negative predictive value for the diagnosis of abdominal and thoracic findings were 63.3%, 100%, 100%, and 40%, respectively. Most main diagnostic findings were detected using the mobile device compared to the high-end ultrasound. Limitations were found regarding characterization and classification of hepatic and renal tumorous lesions.Image quality revealed mostly minor diagnostic limitations for the mobile device, mean 2.9 (SD ± 0.300) and was excellent or with only minor diagnostic limitations for conventional high-end ultrasound, mean 3.25 (SD ± 0.438). CONCLUSION: Due to its easy application and its high diagnostic reliability, point-of-care ultrasound systems of the latest generation represent a valuable imaging method for the primary assessment of abdominal and thoracic findings, especially in patients on intensive care units or in emergency situations.

[Surgical treatment of intracaval tumor relapse after radical tumor nephrectomy in locally advanced renal cell carcinoma]. / Chirurgische Therapie des intrakavalen Tumorrezidivs nach radikaler Tumornephrektomie lokal fortgeschrittener Nierenzellkarzinome.

BACKGROUND: About 4-10% of patients with renal cell carcinoma (RCC) demonstrate intracaval tumor thrombi at the time of diagnosis. Furthermore, 2-3% of patients might develop local relapses of which intracaval recurrences represent a rare event with fewer than 15 cases reported in the literature. We report the diagnosis, surgical technique, perioperative complications, and oncological outcome in an additional 6 cases. PATIENTS AND METHODS: Between 2008 and 2019, 6 patients were treated with isolated intracaval relapse of RCC. All patients had undergone radical nephrectomy with thrombectomy in the past. The mean time between first surgery and relapse was 45.2 (6-114) months and the mean age of patients was 75 (70-80) years: 2, 3 and 1 patient demonstrated thrombus level II, III, and IV, respectively. A thoracoabdominal and a transperitoneal surgical approach was chosen in 4 and 2 patients, respectively. Perioperative complications were reported according to the Clavien-Dindo classification. Relapse-free, cancer-specific and overall survival were calculated with the Kaplan-Meier method. RESULTS: The cava thrombus could be resected completely in all cases. The mean time of surgery was 330 (260-510) min and the mean blood loss was 1500 (300-6500) ml. Clavien-Dindo grade II and IV complications developed in 2 and 1 patients, respectively. The 90-day readmission rate and mortality were 0%. After a mean follow-up of 32.3 (6-96) months, 5 patients are relapse-free and 1 patient developed pulmonary and hepatic metastases managed by immuno-oncological therapy. One patient died 27 months postoperatively due to multiple myeloma. CONCLUSION: Secondary thrombectomy for isolated intracaval tumor thrombus relapse represents a challenging surgery which is associated with a high oncological control rate and tolerable surgery-related morbidity. This type of surgery should be performed in centres with significant expertise in radical nephrectomy for locally advanced disease and thrombus surgery.

ETS-dependent p16INK4a and p21waf1/cip1 gene expression upon endothelin-1 stimulation in malignant versus and non-malignant proximal tubule cells.

AIM: Cellular senescence, leading to cell death through prevention of regular cell renewal, is associated with the upregulation of the tumor suppressor gene p16(INK4a). While this mechanism has been described as leading to progressive nephron loss, p16(INK4a) upregulation in renal cell carcinoma has been linked to a disease-specific improved patient survival rate. While in both conditions endothelin-1 is also upregulated, the signaling pathway connecting ET-1 to p16(INK4a) has not been characterized until this study. MAIN METHODS: Cell culture, qRT-PCR, Western Blot, immunoprecipitation (IP), proximity ligation assay (PLA), and non-radioactive electrophoretic mobility shift assay (EMSA). KEY FINDINGS: In malignant renal proximal tumor cells (Caki-1), an activation of p16(INK4a) and p21(waf1/cip1) was observed. An increased expression of E-26 transformation-specific (ETS) transcription factors was detectable. Using specific antibodies, a complex formation between ETS1 and extracellular signal-regulated kinase-2 (ERK2) was shown. A further complex partner was Mxi2. EMSA with supershift analysis for ETS1 and Mxi2 indicated the involvement of both factors in the protein-DNA interaction. After specifically blocking the endothelin receptors, ETS1 expression was significantly downregulated. However, the endothelin B receptor dependent downregulation was stronger than that of the A receptor. In contrast, primary proximal tubule cells showed a nuclear decrease after ET-1 stimulation. This indicates that other ETS members may be involved in the observed p16(INK4a) upregulation (as described in the literature). SIGNIFICANCE: ETS1, ERK2 and Mxi2 are important complex partners initiating increased p16(INK4a) and p21w(af1/cip1) activation in renal tumor cells.