A MassQL-Integrated Molecular Networking Approach for the Discovery and Substructure Annotation of Bioactive Cyclic Peptides.

The marine sponge-derived fungus Stachylidium bicolor 293 K04 is a prolific producer of specialized metabolites, including certain cyclic tetrapeptides called endolides, which are characterized by the presence of the unusual amino acid N-methyl-3-(3-furyl)-alanine. This rare feature can be used as bait to detect new endolide-like analogs through customized fragment pattern searches of tandem mass spectrometry data using the Mass Spec Query Language (MassQL). Here, we integrate endolide-specific MassQL queries with molecular networking to obtain substructural information guiding the targeted isolation and structure elucidation of the new proline-containing endolides E (1) and F (2). We showed that endolide F (but not E) is a moderate antagonist of the arginine vasopressin V1A receptor, a member of the G protein-coupled receptor superfamily.

Surgical management of complicated Descemet's membrane detachment in corneas without prior endothelial keratoplasty.

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.

The Hemodynamic Performance of the Perceval Sutureless Aortic Valve in a Propensity-Matched Comparison to the Carpentier-Edwards Perimount and Perimount Magna Ease Valves for Aortic Valve Replacement.

OBJECTIVES: The Perceval valve was shown to facilitate minimal-invasive operations and shorten operative times. We aimed to compare the early results of the Perceval valve to those of well-established valves, namely the Carpentier-Edwards Perimount and Perimount Magna Ease valve protheses, in terms of their clinical and hemodynamic performances. METHODS: This is a single-center, retrospective, observational cohort study. For every patient operated with a Perceval valve, the last patient before and the next following patient receiving a Perimount valve was included in a control group leading to a 2:1 ratio (Perimount:Perceval). A propensity score matching was used and a subgroup analysis was performed to compare early and late Perceval patients as the sizing technique was changed over time. RESULTS: From November 2013 to November 2017, 423 patients were identified. These included 141 consecutive patients receiving a Perceval valve through a full- or a hemi-sternotomy. In addition, 282 patients receiving a Perimount or a Magna Ease valve were enrolled. After propensity score matching, 127 matched patients were compared. Operating times were shorter and postoperative transvalvular pressure gradients were lower in the Perceval group (15 vs. 17 mmHg, p = 0.002). There was no difference in mortality and stroke rates. The incidence of new pacemaker implantations was higher in the Perceval group (7.1 vs. 18.9%, p = 0.005), mainly due to a very high incidence in the early phase of our Perceval experience prior to a change in the Perceval implantation technique. Subgroup analysis showed significantly better results in the late Perceval group. CONCLUSION: Surgical outcome was good in both groups. The Perceval valve exhibited lower postoperative gradients, and the need for pacemaker implantation was higher and can be reduced by avoiding oversizing.

Clinical Outcomes after Mitral Valve Surgery in Failed MitraClip Procedures.

BACKGROUND: We retrospectively evaluated in-hospital and overall outcome of patients who received mitral valve replacement (MVR) after failed MitraClip procedure. METHODS: A total of 26 out of 740 patients received MVR after treatment with MitraClip between June 2010 and December 2020. We analyzed in-hospital mortality and overall mortality during the median follow-up period of 72 days after MVR. RESULTS: The median age in the entire cohort was 77.5 years. In-hospital mortality was 15.4% (n = 4) and the overall mortality during the follow-up period was 27% (n = 7). The median time between the MitraClip procedure and surgery was 34.5 days. The main reasons for surgery were mitral stenosis (23.1%), persistent prolapse of the mitral valve leaflets (42.3%), and persistent tethering of the mitral valve leaflets (34.6%). At the time of surgery all of the patients presented with New York Heart Association 3 and above. The underlying mitral valve pathology was mainly secondary 61.5% (n = 16). Median left ventricular end-diastolic diameter was 60 mm. Preoperative ejection fraction was 40% and above in 73% of the cohort. In addition to the mitral valve procedure, 57.7% of patients received either concomitant tricuspid annuloplasty, aortic valve surgery, ascending aortic replacement, or coronary artery bypass grafting. CONCLUSION: The need for MVR for failed MitraClip repair is low and the results are acceptable. However, remaining options for reconstruction are usually limited and MVR is often needed. Anticipating success or failure according to the underlying pathology more than according to concomitant risk factors should form the basis in decision making for the treatment modality of first choice.

Recurrent Filamentous Fungal Keratitis Caused When the Primarily Selected Graft Diameter was Too Small.

PURPOSE: To establish the importance of using a sufficiently large corneal graft in primary penetrating keratoplasty in order to prevent recurrence of fungal keratitis. OBERSERVATIONS: A 58-year-old female patient underwent emergency penetrating keratoplasty (diameter 7.0 mm, double running suture) for therapy-resistant fungal keratitis (Fusarium solani) at an external eye clinic. Despite intensive antifungal therapy, new fungal infiltrates appeared in the host cornea after a few days. The patient was referred to our department for further treatment. On first presentation, circular infiltrates were seen around the corneal graft with anterior chamber involvement and therapy-resistant hypopyon. We performed an emergency penetrating repeat keratoplasty (diameter of 13.0 mm, 32 interrupted sutures) combined with anterior chamber lavage and intracameral and intrastromal drug injection. CONCLUSION AND IMPORTANCE: Fungal keratitis sometimes has a frustrating clinical course. Therefore, early diagnosis with effective therapy initiation is of the utmost importance. In cases of penetrating keratoplasty, optimal planning and timing (before anterior chamber involvement) should be provided. Sufficient safety distance must be ensured in the choice of graft diameter, fixation with multiple interrupted sutures, and anterior chamber lavage, as well as intracameral and intrastromal drug administration. Incomplete excision carries a risk of recurrence and endophthalmitis in the course. Close postoperative control is necessary to detect early recurrences.

Ultrastructural Examination of the Corneal Interface after Predescemetic Deep Anterior Lamellar Keratoplasty (DALK) - A Case Report with Light and Transmission Electron Microscopy.

PURPOSE: To examine corneal buttons with light and transmission electron microscopy (TEM) to visualize the interface area and highlight the ultrastructural corneal changes after deep anterior lamellar keratoplasty (DALK). METHODS: Two patients underwent excimer laser-assisted penetrating repeat keratoplasty after predescemetic DALK. The corneal buttons were examined by light microscopy and TEM. RESULTS: The light microscopic examination of the corneal buttons revealed fragments of a second Descemet's membrane in the central and midperipheral areas (Case 1). In both cases, visualization of the interface area was not possible by light microscopy. The donor and host stroma were tightly attached without dehiscence. TEM identified the interface area by irregularities in the collagen distribution between the donor and host stroma. The thickness of the remaining recipient corneal stroma measured approximately 30 µm (Case 1) and 100 µm (Case 2), respectively. In the host stroma, TEM revealed the absence or degeneration of keratocytes, accumulation of amorphous material between the collagen lamellae, and vacuolar inclusions dispersed in the stroma, forming a band-like zone anterior to Descemet's membrane. CONCLUSION: The interface area after DALK has been mainly investigated by in vivo confocal microscopy. Light microscopy and TEM findings indicate remodeling processes after DALK that are associated with increased keratocyte degeneration and structural alterations of the extracellular matrix in the host stroma. The choice of surgical method may influence the postoperative morphological and functional outcome since these findings were primarily apparent in the remaining host stroma. Therefore, complete exposure of Descemet's membrane is an important prognostic factor for the postoperative visual outcome.

Corneal Perforation as a Rare and Late Manifestation of Choroidal Melanoma.

PURPOSE: To report a case of corneal perforation as a rare and late manifestation of choroidal melanoma and to highlight the major histopathological findings of this unusual combined clinical presentation. METHODS: A 74-year-old male patient presented to our department due to corneal perforation of the right eye with the absence of light perception for 6 months. The intraocular pressure was hard on palpation. Because of the protracted finding and reduced visual prognosis, primary enucleation was performed. RESULTS: The histopathological examination revealed choroidal melanoma with epithelioid and spindle cell components at the posterior pole, which was positive for Melan-A, Human Melanoma Black 45 (HMB45), BAP1, and SOX10. The anterior segment showed complete anterior chamber hemorrhage and blood remnants in the trabecular meshwork. The cornea displayed diffuse blood staining with hemosiderin and hemosiderin-loaded macrophages and keratocytes. No inflammatory cells were present near the corneal perforation, which had a width of 3 mm. Intraocular heterotopic ossification was indicative of a long-standing condition. Postoperative cancer staging was normal. CONCLUSION: Corneal perforation should be considered as a very rare and late manifestation of advanced choroidal melanoma and may result from interaction between intraocular hemorrhage, elevated IOP, and its secondary signs such as corneal blood staining.

In-Hospital Outcomes Following Surgical Revascularization of Chronic Total Coronary Occlusions.

Background and Objectives: Patients with chronic total occlusions of the coronary arteries are either treated with PCI or referred for surgical revascularization. We analyzed the patients with chronic occluded coronary arteries that were surgically treated and aimed to describe the anatomical characteristics, revascularization rates, and in-hospital outcomes achieved with coronary artery bypass grafting. Methods: Angiographic data of 2005 patients with coronary artery disease treated in our institution between January 2005 and December 2014 were retrospectively analyzed. A total of 1111 patients with at least one coronary total occlusion were identified. We reviewed the preoperative coronary angiograms and surgical protocols to determine the presence, localization, and revascularization of coronary occlusions. We also evaluated the perioperative data and in-hospital outcomes. Results: The median age of the study population was 68 years (25th-75th percentiles, 61.0-74.0). Three-vessel disease was present in 94.8% of patients and the rest (5.8%) had a two-vessel disease. The localizations of the occlusions were as follows: 68.4% in the RCA system, 26.4% in the LAD, and 28.5% in the LCX system. Multiple occlusions were present in 22.6% of the patients. Complete coronary total occlusion revascularization was achieved in 86.1% of the patients. The overall in-hospital mortality was 2.3%. The median in-hospital stay was 14.0 days. After logistic regression analysis, age (odds ratio 3.44 [95% confidence interval, 1.81-6.53], p < 0.001, for a 10-year increase) and the presence of peripheral artery disease (odds ratio 3.32 [1.39-7.93], p = 0.007) were the only statistically significant independent predictors of in-hospital mortality. Conclusions: A high revascularization rate and favorable in-hospital outcomes are achieved with coronary artery bypass surgery in patients with multi-vessel diseases and coronary total occlusions. Older age and the presence of peripheral artery disease are independent predictors of in-hospital mortality. A long-term follow-up and the type of graft (arterial vs. venous) used would bring more useful data for this type of revascularization.

Perioperative Mass Transfusion Affects In-Hospital but Not Follow-Up Survival in Patients with Acute Type A Aortic Dissection.

Background and Objectives: The aim of this study was to analyze the influence of mass transfusion on the postoperative outcome and survival in patients presenting with acute Type A aortic dissection. Materials and Methods: Between 2002 and 2020, a total of 505 patients were surgically treated for an acute Type A aortic dissection. Mass transfusion was defined as the peri- and postoperative replacement by transfusion of 10 units. Patient characteristics and outcomes were analyzed and compared between patients with and without mass transfusion. Results: Mass transfusion occurred in 105 patients (20%). The incidences of symptomatic coronary malperfusion (p = 0.017) and tamponade (p = 0.043) were higher in patients with mass transfusion. There was no statistically significant difference in the distal extension of the aortic dissection between the two groups. A valved conduit was significantly more common in patients with mass transfusion (p = 0.007), while the distal aortic repair was similar between the two groups. Cardiopulmonary bypass time (p < 0.001), cross clamp time (p < 0.001) and in-hospital mortality were significantly higher in patients with mass transfusion (p < 0.001), but the survival after discharge (landmark-analysis) showed equal survival between patients with and without mass transfusion (log rank: p = 0.4). Mass transfusion was predictive of in-hospital mortality (OR: 3.308, p < 0.001) but not for survival after discharge (OR: 1.205, p = 0.661). Conclusions: Mass transfusion is necessary in many patients with acute Type A aortic dissection. These patients present sicker and require longer surgery. However, mass transfusion does not influence survival after discharge.

Training in Aortic Arch Surgery as a Blueprint for a Structured Educational Team Approach: A Review.

Background and objectives: The treatment of pathologies of the aortic arch is a complex field of cardiovascular surgery that has witnessed enormous progress recently. Such treatment is mainly performed in high-volume centres, and surgeons gain great experience in mastering potential difficulties even under emergency circumstances, thereby ensuring the effective therapy of more complex pathologies with lower complication rates. As the numbers of patients rise, so does the need for well-trained surgeons in aortic arch surgery. But how is it possible to learn surgical procedures in a responsible way that, in addition to surgical techniques, also places particular demands on the overall surgical management such as perfusion strategy and neuro-protection? This is why a good training programme teaching young surgeons without increasing the risk for patients is indispensable. Our intention was to highlight the most challenging aspects of aortic arch surgery teaching and how young surgeons can master them. Materials and Methods: We analysed the literature to find out which methods are most suitable for such teaching goals and what result they reveal when serving as teaching procedures. Results: Several studies were found comparing the surgical outcome of young trainees with that of specialists. It was found that the results were comparable whether the procedure was performed by a specialist or by a trainee assisted by the specialist. Conclusions: We thus came to the conclusion that even for such a complex type of intervention, the responsible training of young surgeons by experienced specialists is possible. However, it requires a clear strategy and team approach to ensure a safe outcome for the patient.

Invasive Coronary Angiography in Patients with Native or Prosthetic Aortic Valve Endocarditis.

BACKGROUND: Invasive coronary angiography (ICA) is essential to detect significant coronary artery disease (CAD) but is generally not recommended in patients with infective aortic valve endocarditis. This study aimed to evaluate the risks and benefits of preoperative ICA in patients before aortic valve replacement. METHODS: Between March 2008 and September 2020, 232 patients were surgically treated for infectious endocarditis of the aortic valve. Sixty-seven (29%) of them underwent preoperative diagnostic ICA and were compared with the patients without preoperative ICA. We collected their baseline characteristics, including the neurological status, previous cardiac surgical procedures, and reviewed the preoperative echocardiograms and the ICA data. The intraoperative data and clinical outcomes after ICA and after surgery were evaluated. RESULTS: ICA revealed a CAD in the majority of our patients (n = 36; 54%): One-vessel disease n = 19 (28%), two-vessel disease n = 6 (9%), and three-vessel disease n = 11 (16%). We observed no adverse events following preoperative diagnostic ICA, particularly no thromboembolic complications, including stroke, visceral, or lower body ischemia were detected. During surgical aortic valve replacement, concomitant coronary artery bypass grafting was performed in 20 patients (30%). In patients with preoperative ICA, postoperative in-hospital mortality was significantly lower (n = 8 [12%] vs. n = 30 [18%]; p < 0.001), while the incidence of postoperative bleeding was higher (n = 18 [27%] vs. n = 22 [13%]; p = 0.022). The new-onset stroke incidence was 5% in each group. CONCLUSION: Taking a multidisciplinary team approach, ICA is safe in selected patients with aortic valve infectious endocarditis with no adverse clinical outcomes, but significant clinical implications.

Moderate or Severe Functional MR and Severe AS: Is Mitral Valve Surgery Justified?

OBJECTIVE: Mitral regurgitation (MR) and severe aortic valve stenosis often coexist. Concomitant replacement of both valves is associated with a significantly higher morbidity and mortality. This study sought to investigate the progression of MR after isolated aortic valve replacement. METHODS: We analyzed the severity and progression of MR, survival and echocardiographic parameters in 506 patients with severe aortic valve stenosis and moderate to severe functional MR who received isolated aortic valve replacement during a 9-year period. RESULTS: Transcatheter aortic valve implantation (TAVI) was performed in 381 patients and 125 patients received surgical aortic valve replacement (SAVR). The median age of the cohort was 82 years. Median ejection fraction before and after TAVI or SAVR was 35 and 36% respectively (p = 0.64). There was a statistically significant reduction in the MR (p < 0.001) within both groups. Survival in both groups at 5 years was at 25%. CONCLUSION: Isolated aortic valve replacement in patients with accompanying moderate to severe functional MR may present an adequate treatment option for this high-risk patient collective.

Diameter Changes in Traumatic Aortic Injury: Implications for Stent-Graft Sizing.

OBJECTIVES: The aim of this study was to compare aortic diameters from admission computed tomography angiography (CTA) scans to postoperative aortic diameters in patients with traumatic aortic injury (TAI) and evaluate the influence of substantial blood loss on aortic diameter. METHODS: The aortic databases of two tertiary university centers were retrospectively screened for patients with TAI between February 2002 and February 2019. Concomitant organ injuries, bone fractures, blood loss, and clinical outcomes were evaluated. Aortic diameters were measured in CTA upon admission and were compared with the CTA before discharge at three different aortic levels (mid-ascending, 5 cm distal to the end of the stent graft, and at the celiac trunk level). RESULTS: We identified 45 patients, aged 43 (first quartile; third quartile [26; 55]) years with a TAI treated by thoracic endovascular aortic repair. The most frequent cause of TAI was a car accident (n = 24). Concomitant injuries were seen in all but one patient. Bone and pelvic fractures were seen in 40 (89%) and 15 (33%) patients, respectively. Type III aortic injury was present in 25 patients (56%). Increase of aortic diameter after stabilization was +1.7 mm (-0.6 mm; 2.5 mm; p = 0.004) at the mid-ascending aorta, +2.1 mm (0.2 mm; 3.8 mm; p < 0.001) 5 cm distal to the stent graft, and +1.5 mm (0.5 mm; 3.2 mm; p < 0.001) at the celiac trunk level. CONCLUSION: In patients with TAI, the aortic diameter is significantly reduced as compared with the aortic diameter at discharge. The reduction of aortic diameter might be caused by hemorrhagic shock and should be kept in mind for appropriate stent-graft sizing.

Subsequent cardiac surgery after transcatheter aortic valve implantation: Indications and outcomes.

BACKGROUND: Aim of this study was to report on indications and clinical outcomes of patients who underwent subsequent open-cardiac surgery after transcatheter aortic valve implantation TAVI. METHODS: Between 01/2011 and 12/2020 our centre performed 4043 TAVI procedures. Twenty-seven patients (including patients in whom TAVI was performed in other centres) underwent subsequent open-heart surgery via cardiopulmonary bypass. Demographic, intraprocedural data, indications for, and outcomes after surgery were evaluated. RESULTS: Indications for cardiac surgery (aged 79 [IQR 76-84]; 59.3% male) were endocarditis (n = 11; 40.7%), annular rupture, severe paravalvular leak and severe stenosis in three (11.1%) patients, respectively as well as in one patient each (3.7%) severe tricuspid valve regurgitation, valve thrombosis, valve malposition, valve migration, ostial right coronary artery obstruction, left ventricular rupture and type A aortic dissection. The interval between the index TAVI procedure to open surgery was 3 months (IQR 0-26 months). Eight patients underwent emergent surgical conversions. Immediate procedural and procedural mortality was 25.9% and 40.7%, respectively and all-cause mortality was 51.9% (11/12 died for cardiovascular reasons). No disabling stroke was observed postoperatively. New permanent pacemaker implantation was required in three patients (11.1%). CONCLUSIONS: Subsequent open-cardiac surgery after TAVI is rare, but may urgently become necessary due to TAVI related complications or progressing other cardiac pathologies. Despite a substantial early attrition rate clinical outcome is acceptable and a relevant number of these high-risk patients can be discharged even after emergency conversions. The option of subsequent surgical conversion remains.

Infectious Crystalline Keratopathy after Penetrating Keratoplasty with Light and Electron Microscopic Examination.

PURPOSE: To highlight the typical histological and ultrastructural features of severe infectious crystalline keratopathy (ICK) in a corneal graft, which required excimer laser-assisted repeat penetrating keratoplasty (PKP) and to present the challenging treatment conditions associated with ICK. METHODS: An 85-year-old female patient underwent PKP for secondary graft failure after Descemet membrane endothelial keratoplasty (DMEK) for Fuchs' endothelial corneal dystrophy in the left eye. One year later, white branched opacities were observed in the superficial corneal stroma of the graft without surrounding inflammation in the left eye. The patient underwent excimer laser-assisted repeat PKP (8.0/8.1 mm) in the left eye after prolonged refractory topical anti-infectious treatment for 1 month. The corneal explant was further examined by light and transmission electron microscopy (TEM). RESULTS: The light microscopic examination of the corneal explant demonstrated aggregates of coccoid bacteria in the superficial and mid-stromal region that were positive for periodic acid-Schiff (PAS) and Gram stain. The bacterial aggregates extended into the interlamellar spaces, showed a spindle-shaped appearance, and were not surrounded by an inflammatory cellular reaction. TEM demonstrated lamellae separation within the anterior corneal stroma with spindle-shaped aggregates of bacteria, which were embedded in an extracellular amorphous matrix with incipient calcification, being consistent with a biofilm. No inflammatory cellular reaction was evident by TEM. At discharge from hospital, the corrected visual acuity was 20/80 in the left eye. CONCLUSION: ICK is often challenging due to the difficult diagnosis and treatment conditions. The refractory courses are mainly attributed to a biofilm formation, which inhibits effective topical anti-infectious treatment. In such cases, (repeat) PKP may be necessary to completely remove the pathology, prevent recurrences, and improve vision.

Simultaneous Bilateral Primary Occlusion of the Ophthalmic Artery due to Florid Giant Cell Arteritis.

PURPOSE: To report a case of simultaneous bilateral ophthalmic artery occlusion in diagnosed giant cell arteritis (GCA). OBSERVATIONS: A 77-year-old male patient presented to the emergency department with simultaneous vision loss in both eyes for 3 hours. Headache at both temples and jaw claudication had been present for 3 weeks. Laboratory values demonstrated an initially increased C-reactive protein (CRP) of 202.0 mg/L and an erythrocyte sedimentation rate (ESR) of 100 mm within the first 20 minutes. Duplex sonography of the right and left temporal arteries revealed a "halo sign." A case of GCA was suspected, and intravenous high-dose methylprednisolone therapy was immediately administered. The clinical examination revealed a bilateral central retinal artery occlusion and fluorescein angiography showed a hot optic disc in the right eye and patchy choroidal hypoperfusion in both eyes. Biopsy of the left temporal artery was performed, which confirmed a florid temporal arteritis with complete thrombotic occlusion of the vascular lumen. Despite a good response to the administered therapy (CRP 17.0 mg/L 1 week after initiation), the visual prognosis was significantly limited through retinal and optic nerve involvement. By the follow-up examination 8 weeks later, the near visual acuity was 20/400 in the right and left eye at a distance of 16 inches. CONCLUSION AND IMPORTANCE: We hereby present a simultaneous bilateral ophthalmic artery occlusion as a rare complication of GCA. The combination of central retinal artery occlusion, arteritic anterior ischemic optic neuropathy, and choroidal hypoperfusion suggests an acute inflammatory involvement of the ophthalmic artery. In cases of the slightest suspicion of giant cell arteritis, an immediate high-dose steroid therapy initiation is of utmost importance.

Descemet Membrane Endothelial Keratoplasty (DMEK) for Severe Verrucous Posterior Polymorphous Corneal Dystrophy with Uncommon Clinical and Ultrastructural Findings.

PURPOSE: To report a case of severe verrucous posterior polymorphous corneal dystrophy (PPCD) and cataract, which was treated with Descemet membrane endothelial keratoplasty (DMEK) and simultaneous cataract surgery as a triple procedure (Triple-DMEK). METHODS: A 62-year-old female patient presented to our department for co-evaluation of advanced PPCD with cataract and progressive light sensitivity in both eyes. The clinical examination demonstrated unusual clinical findings with prominent verrucous lesions on the posterior surface of the cornea without corneal decompensation. We performed a Triple-DMEK in case of simultaneous cataract. The corneal tissue was examined by light and transmission electron microscopy. RESULTS: Intraoperatively, it was difficult to remove the verrucous structures completely after classical descemetorhexis. Light microscopic examination demonstrated epithelium-like transformation of the corneal endothelium by immunostaining (cytokeratin AE1/3 staining). Transmission electron microscopy revealed thickening of Descemet's membrane (18.5 to 30.0 µm). The anterior banded layer had a normal structure and was slightly thickened (3.5 to 5.5 µm). A normal posterior non-banded layer (PNBL) was observed but thinned (2.5 to 4.0 µm) or missing. It was followed by an altered PNBL with abnormal fibrillary inclusions, which was strongly and variably thickened (11.0 to 24.5 µm). The corneal endothelium was degenerated, partially absent, and epithelial-like altered. The nodular lesions were found to consist of a few degenerated cells that were embedded in an amorphous extracellular matrix interspersed with collagen fibers, which were not arranged in regular lamellae, forming the corneal stroma. The occurrence of pigment granules among the cellular debris suggested that the cells were endothelial cells. The corrected distance visual acuity improved from 20/50 to 20/30 in the right eye (+ 0.00/- 1.75/157°) and from 20/60 to 20/30 in the left eye (+ 0.00/- 1.75/33°), with significant improvement in light sensitivity. CONCLUSION: The clinical and ultrastructural findings seem to be an unusual variant of the typical characteristic appearance of a PPCD. This case demonstrates that Triple-DMEK is feasible even in very advanced dystrophic changes of the posterior corneal surface, with good morphological and functional results.

The Frozen Elephant Trunk Technique for the Treatment of Type B and Type Non-A Non-B Aortic Dissection.

OBJECTIVE: To evaluate outcomes of patients with acute complicated or chronic Type B or non-A non-B aortic dissection who underwent the frozen elephant trunk (FET) technique. METHODS: Between April 2013 and July 2019, 41 patients presenting with acute complicated (n = 29) or chronic (n = 12) descending thoracic aortic dissection were treated by the FET technique, which was the treatment of choice when supra-aortic vessel transposition would not suffice to create a satisfactory proximal landing zone for endovascular aortic repair, when a concomitant ascending or arch aneurysm was present, or in patients with connective tissue diseases. RESULTS: One patient (2%) died intra-operatively secondary to an aortic rupture in dwnstream aortic segments. No post-operative deaths occurred. Four patients (10%) suffered a non-disabling posto-operative stroke and were discharged with no clinical symptoms (modified Rankin Scale [mRS] 0, n = 1), no significant disability (mRS 1, n = 2), or with slight disability (mRS 2, n = 1). No spinal cord ischaemia was observed. The primary entry tear was either surgically resected or excluded from circulation in all patients. During follow up, one patient (2%) died after two years (not aorta related) and 16 patients (39%) underwent an aortic re-intervention after 7.7 [interquartile range 0.7, 15.8] months (endovascular aortic repair: n = 14; open thoraco-abdominal aortic replacement: n = 1, hybrid approach: n = 1). CONCLUSION: The FET technique is an effective treatment option for acute complicated and chronic Type B or non-A non-B aortic dissection in patients in whom primary endovascular aortic repair is non-feasible. While the post-operative outcome is acceptable with a relatively low incidence of non-disabling strokes, this study also underlines the considerable need for aortic re-interventions. Continuous follow up of all patients undergoing the FET procedure is essential.

NF-κB, iNOS, IL-6, and collagen 1 and 5 expression in healthy and keratoconus corneal fibroblasts after 0.1% riboflavin UV-A illumination.

PURPOSE: To analyze the effect of riboflavin UV-A illumination on mRNA and protein expression of healthy (HCFs) and keratoconus human corneal fibroblasts (KC-HCFs), concerning the inflammatory markers NF-κB, iNOS, IL-6, and collagen 1 and 5 (Col 1/Col 5). METHODS: Keratocytes were isolated from healthy (n = 3) and keratoconus (KC) corneas (n = 3) and were cultivated in basal medium with 5% fetal calf serum, which resulted in their transformation into human corneal fibroblasts (HCFs/KC-HCFs). Cells underwent 0.1% riboflavin UV-A illumination for 250 s (CXL). NF-κB, iNOS, IL-6, Col 1, and Col 5 expression was investigated by qPCR and Western blot analysis. IL-6 concentration of the cell culture supernatant and cell lysate was determined by ELISA. RESULTS: In untreated KC-HCFs, NF-κB (p = 0.0002), iNOS (p = 0.0019), Col 1 (p = 0.0286), and Col 5 (p = 0.0054) mRNA expression was higher and IL-6 expression was lower (p = 0.0057), than in healthy controls. In HCFs, CXL led to an increased NF-κB (p = 0.0286) and IL-6 (p = 0.0057) mRNA expression. The IL-6 concentration in the cell culture supernatant was increased in HCFs (p = 0.0485) and KC-HCFs (p = 0.0485) after CXL. CXL increased intracellular IL-6 concentration only in KC-HCFs (p = 0.0357). In the HCF group (p = 0.0286), an increased Col 1 mRNA expression after CXL could be observed. CONCLUSION: Our study confirmed altered gene expression in untreated KC-HCFs compared to untreated HCFs. Riboflavin UV-A illumination affected gene expression only in HCFs. Increased IL-6 concentration in the cell culture supernatant and cell lysate indicate a secondary inflammatory response of HCFs and KC-HCFs to riboflavin UV-A illumination.

What Is the Best Method to Achieve Safe and Precise Stent-Graft Deployment in Patients Undergoing TEVAR?

Thoracic endovascular aortic repair (TEVAR) for aortic pathologies requires sufficient landing zone of ideally more than 25 mm for safe anchoring of the stent-graft and prevention of endoleaks. In the aortic arch and at the thoracoabdominal transition, landing zone length is usually limited by the offspring of the major aortic side-branches. Exact deployment of the stent-graft to effectively use the whole length of the landing zone and to prevent occlusion of one of the side-branches is key to successful TEVAR. There are numerous techniques described to lower blood pressure and to reduce or eliminate aortic impulse to facilitate exact deployment of stent-grafts including pharmacologic blood pressure lowering, adenosine-induced asystole, inflow occlusion, and rapid pacing. Aim of this review was to assess the current literature to identify which of the techniques is best suited to prevent displacement and allow for precise placement of the stent-graft and safe balloon-molding.