Immunhistochemische Befunde retrokornealer Membranen von Augen mit kornealer Dekompensation nach komplizierten intraokularen Eingriffen

BACKGROUND Retrocorneal membranes (RCMs) may result from epithelial ingrowth, stromal keratocytic downgrowth, fibrous metaplasia of the corneal endothelium, or a combination of these processes. In an institutional case series, the clinical history, ocular findings, and immunohistochemical staining results of RCMs were analysed in patients with unilateral corneal decompensation after complicated intraocular surgery. METHODS AND PATIENTS Between January 2021 and September 2022, six retrocorneal membranes were excised during Descemet's stripping automated endothelial keratoplasty (DSAEK) and Descemet membrane endothelial keratoplasty (DMEK) procedures and classified after screening with haematoxylin and eosin, periodic acid-Schiff, elastic van Gieson staining, and immunohistochemical screening with cytokeratin 7 (CK7), anti-cytokeratin (CAM5.2 and AE1/3), cell surface glycoprotein CD34, smooth muscle actin (α-SMA), and vimentin. RESULTS On the basis of the immunohistochemical screening, the majority of excised RCMs (5 of 6) could histopathologically be classified as membranes originating from fibrous metaplasia of the corneal endothelium. All these RCMs were positive for CK7, α-SMA, and vimentin and negative for CAM5.2 and CD34. In one patient, an RCM had developed after 18 days of corneal contact to a free-floating dexamethasone implant in the anterior chamber and was classified as originating from stromal keratocyte downgrowth (α-SMA- and vimentin-positive, all others negative). All eyes in this series had a previous history of complicated cataract surgery, partially with subsequent intraocular lens exchange. No eyes after previous penetrating keratoplasty were in this series. CONCLUSIONS In this series of eyes with previous complicated intraocular interventions (in most cases cataract surgery and revisions), the dominating RCM belonged to the type originating from fibrous metaplasia of the corneal endothelium

Identification of New Players in Hepatocarcinogenesis: Limits and Opportunities of Using Tissue Microarray (TMA)

Liver tumours are among the leading causes of cancer-related death worldwide and hepatocellular carcinoma (HCC) accounts for the vast majority of liver tumours. When detected at an early stage of disease, patients might still be eligible for surgical-based curative treatments. However, currently only small portion of HCC affected patients are diagnosed at an early stage. For late stage HCC no treatment option exists beside the multi-tyrosine kinase inhibitor Sorafenib. Thus new molecular targets and treatment options for HCC are urgently needed. Nevertheless, despite some improvements in diagnosis and patient management, the biology of liver tumour remains inadequately understood, mainly because these tumours have shown to harbour a highly complex genomic landscape. In addition, one major obstacle delaying the identification of new molecular targets in biomedical research is the necessity to validate them using a large collection of tissue specimens. Tissue microarray (TMA) technology allows the prompt molecular profiling of multiple tissue specimens and is therefore ideal to analyze presumptive candidate biomarkers in a fast an effective manner. The use of TMA has substantial benefits over standard techniques and represents a significant advancement in molecular pathology. For example, TMA technology reduces laboratory work, offers a high level of experimental uniformity and provides a judicious use of precious tissue. On the other hand, one potential limitation of using TMA is that the small cores sampled may not be representative of whole tumors. This issue is very critical in particularly heterogeneous cancers such as HCC. For liver focused studies, it is ideal to evaluate the staining patters of a determined marker over the structure of an entire acinus and to define staining in as many as possible anatomical regions. In this review we analyze the limits and opportunities offered by the usage of TMA technology in HCC research. In summary, TMA has revolutionized the histopathological analysis and will be of great help to further advance the knowledge in the field of hepatocarcinogenesis research

Heart rate variability and stroke or systemic embolism in patients with atrial fibrillation.

BACKGROUND Stroke remains one of the most serious complications in atrial fibrillation (AF) patients and has been linked to disturbances of the autonomic nervous system. OBJECTIVE We hypothesized that impaired cardiac autonomic function might be associated with an enhanced stroke risk in AF patients. METHODS We enrolled 1922 AF patients who were either in sinus rhythm (SR-group, n=1121) or AF (AF-group, n=801) on a 5-minute resting ECG recording. HRV triangular index (HRVI), standard deviation of normal-to-normal intervals, root mean square root of successive differences of normal-to-normal intervals, mean heart rate, 5-min total power and power in the high frequency, low frequency and very low frequency range were calculated. We constructed Cox regression models to examine the association of HRV parameters with the composite endpoint of stroke or systemic embolism. RESULTS Mean age was 71±8 years in the SR group and 75±8 in the AF group. 37 patients in the SR group (3.4%) and 60 patients in the AF group (8.0%) experienced a stroke or systemic embolism during a follow-up time of 5 years. In patients with SR, HRVI <15 was the strongest HRV parameter to be associated with stroke or systemic embolism (hazard ratio 3.04; 95% confidence interval 1.3-7.0; p=0.009) after adjustment for multiple confounders. In the AF group, we found no HRV parameter to be associated with the composite endpoint. CONCLUSION HRVI measured during SR on a single 5-minute ECG recording is independently associated with stroke or systemic embolism in AF patients. HRV analysis in SR may help to improve risk stratification in AF patients

Liver damage and senescence increases in patients developing hepatocellular carcinoma

Most patients with a hepatocellular carcinoma (HCC) have an underlying chronic liver inflammation, which causes a continuous damage leading to liver cirrhosis and eventually HCC. However, only a minority of cirrhotic patients develop HCC. To assess a possible differential impact of liver inflammation in patients developing HCC versus patients remaining tumor-free, we designed a longitudinal study and analysed liver tissue of the same patients (n = 33) at two points in time: once when no HCC was present and once several years later when an HCC was present. As a control group, we followed cirrhotic patients (n = 37) remaining tumor-free over a similar time frame.; We analysed cell damage and senescence of hepatocytes by measuring γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, nuclear size, and telomere length.; γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, in the first liver biopsy was similar in patients developing HCC later on and cirrhotic patients remaining tumor free. In contrast, γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, was significantly higher in the second non-tumoral liver biopsy of HCC patients than in the control patients. Consequently, the individual increase in γ-H2AX positivity, p16INK4 and p21WAF/Cip1 expression, from the first biopsy to the second biopsy was significantly higher in patients developing HCC than in patients remaining tumor free. In addition, changes in nuclear size and telomere length revealed a more pronounced cell aging in patients developing HCC than in patients remaining tumor free.; Hepatocytes from patients developing HCC go through more pronounced cell damage and senescence in contrast to cirrhotic patients remaining tumor free

Topical nasal steroid treatment does not improve CPAP compliance in unselected patients with OSAS

Continuous positive airways pressure (CPAP) for treatment of obstructive sleep apnea (OSA) can produce troublesome nasal symptoms (i.e. congestion, rhinorrhea) that may reduce the compliance of CPAP. Topical nasal steroids are often prescribed to reduce these side effects, although scientific data are scarce supporting any benefits of this treatment for CPAP-induced nasal side effects