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Lung cancer is the leading cause of cancer-related deaths in the western world. Squamous cell carcinoma is one of the most common histological subtypes of this malignancy. For squamous cell carcinoma of the lung (LSCC), prognostic and predictive markers still are largely missing. In a previous study, we were able to show that the expression of THSD7A shows an association with unfavorable prognostic parameters in prostate cancer. There is also a link to a high expression of FAK. There is incidence that SCARA5 might be the downstream gene of THSD7A. Furthermore, there is evidence that SCARA5 interacts with FAK. We were interested in the role of SCARA5 as a potential biomarker in LSCC. Furthermore, we wanted to know whether SCARA5 expression is linked to THSD7A positivity and to the expression level of FAK. For this reason, we analyzed 101 LSCC tumors by immunohistochemistry. Tissue microarrays were utilized. No significant association was found between SCARA5 expression and overall survival or clinicopathological parameters. There was also no significant association between THSD7A positivity and SCARA5 expression level. Moreover, no significant association was found between FAK expression level and SCARA5 expression level. SCARA5 seems not to play a major role as a biomarker in squamous cell carcinoma of the lung.

Purpose: To provide insights into morphologic and functional features of eyes with complicated Descemet's membrane detachment (DMD) and report clinical outcomes after surgical intervention., Methods: Retrospective study of 18 eyes with complicated DMD between 2010 and 2022. Complicated DMD was defined if any of the following criteria applied: prior penetrating keratoplasty (PKP), corneal thinning, total DMD or persistent DMD after Air/Gas-Descemetopexy. Causes, surgical management, and clinical outcomes were analyzed. Scheimpflug tomography, anterior segment optical coherence tomography (AS-OCT) and histologic examination were performed to characterize corneas with DMD., Results: Fourteen eyes with prior PKP developed spontaneous DMD after 24.2 ± 12.9 years (range = 18 months - 47 years, median = 25.7 years). Complicated DMD without prior PKP was associated in three eyes after cataract surgery and in one eye after infectious keratitis. In cases with previous PKP, AS-OCT demonstrated rupture of Descemet's membrane (DM) in five eyes and spontaneous reattachment was found in four eyes within 8 weeks of initial diagnosis, with no rupture of DM in any of the cases. There was no rupture of DM in corneas without previous PKP. After prior keratoplasty, definitive surgical treatment was repeat PKP in 13 eyes and Air/Gas-Descemetopexy in one eye. In corneas without prior keratoplasty, three eyes underwent PKP and one eye Air/Gas-Descemetopexy. Histological examination of two corneal explants revealed a severely thinned graft-host junction and a disrupted DM close to the graft-host junction. Visual acuity improved from 1.80 ± 0.58 logMAR to 0.75 ± 0.69 logMAR after prior PKP and from 1.45 ± 0.65 logMAR to 0.85 ± 1.13 logMAR without prior PKP. The postoperative course was uneventful in 16 of 18 eyes., Conclusion: PKP is an effective treatment option for complicated DMD, especially in ectatic corneas, whereas Air/Gas-Descemetopexy or Descemet Membrane Endothelial Keratoplasty do not address the primary issue of the curvature anomaly., (© 2023. The Author(s).)

Respiratory viral infections may have different impacts ranging from infection without symptoms to severe disease or even death though the reasons are not well characterized. A patient (age group 5-15 years) displaying symptoms of hemolytic uremic syndrome died one day after hospitalization. qPCR, next generation sequencing, virus isolation, antigenic characterization, resistance analysis was performed and virus replication kinetics in well-differentiated airway cells were determined. Autopsy revealed hemorrhagic pneumonia as major pathological manifestation. Lung samples harbored a large population of A(H1N1)pdm09 viruses with the polymorphism H456H/Y in PB1 polymerase. The H456H/Y viruses replicated much faster to high viral titers than upper respiratory tract viruses in vitro. H456H/Y-infected air-liquid interface cultures of differentiated airway epithelial cells did reflect a more pronounced loss of ciliated cells. A different pattern of virus quasispecies was found in the upper airway samples where substitution S263S/F (HA1) was observed. The data support the notion that viral quasispecies had evolved locally in the lung to support high replicative fitness. This change may have initiated further pathogenic processes leading to rapid dissemination of inflammatory mediators followed by development of hemorrhagic lung lesions and fatal outcome., Competing Interests: Declaration of Competing Interest All authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Prostate cancer is one of the most common malignancies worldwide, showing a wide range of clinical behaviors. Therefore, several treatment options arise out of the diagnosis "prostate cancer". For this reason, it is desirable to find novel prognostic and predictive markers. In former studies, we showed that THSD7A expression is associated with unfavorable prognostic parameters in prostate cancer and is linked to a high expression of focal adhesion kinase (FAK). Recently, scavenger receptor class A member 5 (SCARA5) was reported to be the downstream gene of THSD7A in esophageal squamous cell carcinoma. SCARA5 is believed to play an important role in the development and progression of several different tumor types. Most studies describe SCARA5 as a tumor suppressor. There is also evidence that SCARA 5 interacts with FAK. To examine the role of SCARA5 as a potential biomarker in prostate cancer, a total of 461 prostate cancers were analyzed via immunohistochemistry using tissue microarrays. Furthermore, we compared the expression level of SCARA5 with our previously collected data on THSD7A and FAK. High SCARA5 expression was associated with advanced tumor stage ( p < 0.001), positive nodal status ( p < 0.001) and high Gleason-score ( p < 0.001). At least, strongly SCARA5-positive cancers were associated with THSD7A-positivity. There was no significant association between SCARA5 expression level and FAK expression level. To our knowledge, we are the first to investigate the role of SCARA5 in prostate cancer and we demonstrated that SCARA5 might be a potential biomarker in prostate cancer.

Lung cancer is the leading cause of cancer-related deaths in the western world, with squamous cell carcinoma being one of the most common histological subtypes. Prognostic and predictive markers are still largely missing for squamous cell carcinoma of the lung (LSCC). Several studies indicate that THSD7A might at least play a role in the prognosis of different tumors. FAK seems to play an important role in lung cancer and is discussed as a potential therapeutic target. In addition, there is evidence that FAK-dependent signaling pathways might be affected by THSD7A. For that reason, we investigated the role of THSD7A as a potential tumor marker in LSCC and whether THSD7A expression has an impact on the expression level of FAK. A total of 101 LSCCs were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity was associated with poor overall survival in female patients and showed a relation to high FAK expression in this subgroup. To our knowledge, we are the first to report these correlations in lung cancer. The results might be proof of the assumed activation of FAK-dependent signaling pathways by THSD7A and that as a membrane-associated protein, THSD7A might serve as a putative therapeutic target in LSCC.

Prostate cancer is one of the most common malignancies, and there are a wide range of treatment options after diagnosis. Most prostate cancers behave in an indolent manner. However, a given sub-group has been shown to exhibit aggressive behavior; therefore, it is desirable to find novel prognostic and predictive (molecular) markers. THSD7A expression is significantly associated with unfavorable prognostic parameters in prostate cancer. FAK is overexpressed in several tumor types and is believed to play a role in tumor progression and metastasis. Furthermore, there is evidence that THSD7A might affect FAK-dependent signaling pathways. To examine whether THSD7A expression has an impact on the expression level of FAK in its unphosphorylated form, a total of 461 prostate cancers were analyzed by immunohistochemistry using tissue microarrays. THSD7A positivity and low FAK expression were associated with adverse pathological features. THSD7A positivity was significantly associated with high FAK expression. To our knowledge we are the first to show that THSD7A positivity is associated with high FAK expression in prostate cancer. This might be proof of the actual involvement of THSD7A in FAK-dependent signaling pathways. This is of special importance because THSD7A might also serve as a putative therapeutic target in cancer therapy.

Background: Epithelial ingrowth is a rare complication after ocular perforation and can become manifest many years after the primary trauma., Case Presentation: A 49-year-old patient presented with a positive Seidel test of unclear origin at her left eye, as well as a sharply defined anterior-stromal corneal scar at both eyes. Prior operations included a bilateral laser-assisted blepharoplasty 3 months earlier. The patient indicated to have been on holiday to France 5 months earlier, during an ongoing oak processionary moth caterpillars infestation. The examination using confocal microscopy confirmed a corneal perforation at the left eye and revealed corneal epithelial ingrowth capped with scarred stroma in both eyes. We performed a penetrating keratoplasty at the left eye. The scarred and perforated host cornea was divided into 4 pieces for further investigation: microbiology (negative), virology (negative), histology and transmission electron microscopy (TEM). Histology revealed differently structured epithelium, centrally inverted into the stroma through defects in Bowman's layer. TEM revealed full thickness corneal perforation with an epithelial plug extending to the lower third of the cornea, but without evidence of epithelial cell migration into the anterior chamber. Our differential diagnosis of the unclear positive Seidel test with epithelial ingrowth was as follows: (1) corneal perforation by hairs of the oak processionary moth caterpillar, although no hairs could be found histologically; (2) corneal perforation during laser-assisted blepharoplasty, which may be supported by the presence of pigmented cells on the posterior surface of Descemet´s membrane, pointing to a possible iris injury., Conclusion: Consequently, we highlighted that contact lenses can be useful, safe and inexpensive protective devices in upper eyelid procedures to protect the cornea against mechanical iatrogenic trauma., (© 2022. The Author(s).)

Purpose: To analyze the histological and (ultra)structural stromal tissue changes after femtosecond (Fs) laser-assisted intracorneal ring segment (ICRS) implantation and their refractive and topographic effects in patients with keratoconus., Methods: This monocentric retrospective case series included 15 consecutive patients with clinical peri-segmental lamellar channel deposits after treatment with Fs-ICRS implantation for keratoconus. The stromal changes were investigated using in vivo confocal microscopy. Two patients underwent a penetrating keratoplasty after the Fs-ICRS implantation; the explanted corneas were processed for histopathology and transmission electron microscopy (TEM). Refractive and topographic effects were investigated comparing the uncorrected (UDVA) and corrected (CDVA) distance visual acuity, spherical equivalent (SE), flat (K1), steep (K2), and steepest (Kmax) keratometry before and after detection of lamellar channel deposits., Results: In vivo confocal microscopy revealed diffuse linear and focal granular hyperreflective structures. Histologically, there was mild proliferation of fibroblasts and fibrosis. TEM demonstrated focal accumulations of degenerated keratocytes with cytoplasmic lipid inclusions. There were no significant changes for UDVA (Δ = 0.0 ± 0.2 logMAR; p = 0.67), CDVA (Δ = 0.0 ± 0.1 logMAR; p = 0.32), SE (Δ 0.1 ± 0.9 D; p = 0.22), K1 (Δ = 0.3 ± 1.0 D; p = 0.28), K2 (Δ = 0.1 ± 0.9 D; p = 0.51), and Kmax (Δ = 0.3 ± 1.5 D; p = 0.17)., Conclusions: Two types of structural stromal changes were identified: (1) diffuse peri-segmental fibrosis and (2) lamellar channel deposits. These structural changes showed no evidence of a relevant refractive or topographic effect., (© 2022. The Author(s).)

Background: We present the results of penetrating keratoplasty (PKP) after previous treatment with a total conjunctival flap in two patients., Case Reports: Patient 1, a 66-year-old with a history of bilateral cement chemical burn in 1986 and external right-sided limbokeratoplasty in 2008 was treated externally with a total conjunctival flap in the right eye in 2014 due to a persistent corneal ulcer with imminent perforation. Best-corrected visual acuity (BCVA) in the right eye was light sensation, intraocular pressure on palpation was within normal range. Clinically, total conjunctival flap was present. Patient 2 was treated externally in May 2015 due to acanthamoeba keratitis in the left eye with a deep anterior lamellar keratoplasty (DALK). A re-DALK was also performed externally in the same month. A third DALK was performed externally in August 2015 due to a persistent corneal ulcer, followed by a total conjunctival flap 2 weeks later. BCVA of the left eye was light sensation and intraocular pressure on palpation was within the normal range., Results: Patient 1 was treated with removal of the conjunctival flap in the right eye and penetrating central re-keratoplasty (hand-held Barron trephine; graft diameter 8.5/8.75 mm). Simultaneously, lens extraction and intraocular lens implantation were performed (as a triple procedure). Additionally, amniotic membrane transplantation (AMT) as patch and a temporal lateral tarsorrhaphy were performed. BCVA 6 months postoperatively was 0.1. The graft was clear, without any signs of rejection. Patient 2 was treated on the left eye with removal of the conjunctival flap and a penetrating central keratoplasty (hand-held Barron trephine; graft diameter 7.0/7.5 mm). An AMT as patch and a temporal lateral tarsorrhaphy were simultaneously performed. Cataract surgery was performed 3 months postoperatively and BCVA of the right eye was 0.1 thereafter. The graft was clear, without any signs of rejection., Conclusion: The conjunctival flap is a treatment of last resort of the (almost) penetrated corneal ulcer, which is to be used only when a keratoplasty is technically impossible. Provided the eye structure and retinal function are preserved, partial visual rehabilitation can possibly be achieved through a PKP after excision of the conjunctival flap, even years after corneal blindness., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Purpose : To analyse the changing trends in penetrating keratoplasty indications between January 2011 and December 2018, at the Department of Ophthalmology, Saarland University Medical Center, Homburg/Saar, Germany. Patients and Methods : This is a retrospective review of 2123 corneal buttons of 1776 patients (1993 eyes, 56.0% males, age at the time of surgery 57.6 ± 18.7 years), who underwent penetrating keratoplasty (PKP) between January 2011 and December 2018. The classification was performed based on histological analysis and using the priority scheme of Brady et al., supplemented by a group of "failed endothelial keratoplasty grafts". Our groups were the following: pseudophakic or aphakic bullous keratopathy, regraft, failed endothelial keratoplasty graft, acute necrotizing and ulcerative keratitis, keratoconus, Fuchs' dystrophy, corneal dystrophy other than Fuchs', corneal scars and other diagnoses. Results : Between 2011 and 2018, keratoconus was the leading indication for PKP in 455 (21.5%) cases, followed by acute necrotizing and ulcerative keratitis in 384 (18.1%), regraft in 367 (17.3%), corneal scars in 350 (16.5%), pseudophakic or aphakic bullous keratopathy in 225 (10.6%), Fuchs' dystrophy in 194 (9.1%), other diagnoses in 64 (3.0%), corneal dystrophy other than Fuchs' in 52 (2.4%), and failed endothelial keratoplasty graft in 32 (1.5%) cases. Conclusions : With the introduction of posterior lamellar keratoplasty, keratoconus remains the leading PKP indication in our center with excimer laser-trephination on a routine basis. A trend towards increasing numbers can be observed regarding acute necrotizing and ulcerative keratitis patients and regrafts. However, the incidence of Fuchs' dystrophy decreased dramatically within PKP patients, with the introduction of posterior lamellar keratoplasty.

In squamous cell carcinoma (SCC) of the lung, mutations within the genes of fibroblast growth factor receptors (FGFR) such as K660N/K660E in FGFR2 and R248C/S249C in FGFR3 and FGFR1 gene amplification have been described, but their prognostic relevance still remains unclear. In order to detect the mutation frequencies and to define their prognostic value for associated clinicopathologic features and survival of patients, resected ΔNp63/p40-positive SCC of the lung (n = 101) were screened for FGFR1 gene amplification by fluorescence in situ hybridization performed on formalin-fixed paraffin embedded tissues and for the presumed driver mutations in genes of FGFR2 and FGFR3 by PCR and Sanger sequencing. Twenty-two of 101 SCCs (22%) were positive for amplification based on a FGFR1/centromere (chromosome 8) ratio > 2.0 or higher. In advanced tumor stages (III-IV), the overall survival of patients carrying FGFR1 gene amplification was significantly higher (p = 0.006). Among women, FGFR1 gene amplification was significantly associated with longer overall survival (p = 0.023). The presence of FGFR1 gene amplification was associated with patient age (65 versus 69 years, p = 0.046), but not with gender, tumor stage, histologic subtype, tumor grade, or ΔNp63/p40 immunoreactivity. The S249C mutation in the FGFR3 gene was identified in one out of 101 SCCs (1%); the K600N, K660E, or R248C mutations were not identified. These results suggest that FGFR1 gene amplification is a frequent alteration in SCC of the lung and appears not to be a negative but rather a favorable prognostic marker for women and particularly for patients with advanced SCC of the lung (stage III-IV).