Adverse Effects of Systemic Immunosuppression in Keratolimbal Allograft

Purpose. Keratolimbal allograft (KLAL) is a treatment for limbal stem cell deficiency. One disadvantage is systemic immunosuppression to avoid rejection. Our purpose was to examine the adverse effects of systemic immunosuppression in KLAL. Methods. A retrospective case review of 16 patients with KLAL who received systemic immunosuppression consisting of a corticosteroid, an antimetabolite, and/or a calcineurin inhibitor was performed. Patients were monitored for signs, symptoms, or laboratory evidence of toxicity. Results. Eleven of 16 patients (68%) experienced an adverse effect. The average age of those with adverse effects was 43.5 years and without was 31.4 years. Ten of 11 patients (91%) had resolution during mean followup of 16.4 months. No serious adverse effects occurred. The most common included anemia, hyperglycemia, elevated creatinine, and elevated liver function tests. Prednisone and tacrolimus were responsible for the most adverse effects. Patients with comorbidities were more likely to experience an adverse effect (82% versus 20%, P = 0.036). Conclusions. KLAL requires prolonged systemic immunosuppression. Our data demonstrated that systemic immunosuppression did not result in serious adverse effects in our population and is relatively safe with monitoring for toxicity. In addition, we demonstrated that adverse effects are more likely in older patients with comorbidities

Early results of coronary artery bypass grafting with coronary endarterectomy for severe coronary artery disease

<p>Abstract</p> <p>Background</p> <p>Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE), it is still used as an adjunct to coronary artery bypass grafting (CABG). This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed.</p> <p>Methods</p> <p>Patient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA), angina pectoris (CCS) and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis.</p> <p>Results</p> <p>Between August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 ± 9 years. A total of 396 vessels were bypassed (4 ± 0.9 vessels per patient). In 98% left internal thoracic artery (LITA) was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA) (n = 55), on left anterior descending artery (LAD) (n = 52) and circumflex artery (RCX) (n = 7). Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%). Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5). During follow-up (24.5 ± 13.4 months), which is 96% complete (4 patients were lost caused by unknown address) 8 patients died (cardiac failure: 3; stroke: 1; cancer: 1; unknown reasons: 3). NYHA-classification significantly improved after CABG with CE from 2.2 ± 0.9 preoperative to 1.7 ± 0.9 postoperative. CCS also changed from 2.4 ± 1.0 to 1.5 ± 0.8</p> <p>Conclusion</p> <p>Early results of coronary endarterectomy are acceptable with respect to mortality, NYHA & CCS. This technique offers a valuable surgical option for patients with endstage coronary artery disease in whom complete revascularization otherwise can not be obtained. Careful patient selection will be necessary to assure the long-term benefit of this procedure.</p

Migraine management for the otolaryngologist

Abstract Objective To characterize migraine pathophysiology, presentation, and current treatment strategies, specifically in regard to vestibulocochlear manifestations of migraine. Methods Narrative review of available literature. Results Migraine disorder can be described as a spectrum of otologic manifestations, with vestibular migraine now recognized with fully‐fledged diagnostic criteria. Otologic manifestations are theorized to be due, in part, to trigeminal innervation of the inner ear structures and calcitonin gene‐related peptide (CGRP) expression within the labyrinth. Patients can experience vertigo, aural fullness, enhanced tinnitus, and hearing loss without the characteristic migraine headache, leading to under recognition of these symptoms as migraine‐related. Meniere's disease, mal de débarquement syndrome, persistent postural perceptual dizziness, and recurrent benign paroxysmal positional vertigo have close associations to migraine and may exist on the migraine spectrum. Migraine treatment consists of two goals: halting acute attacks (abortive therapy) and preventing attacks (prophylactic therapy). Abortive medications include triptans, corticosteroids, anti‐histamines, and anti‐emetics. Pharmacologic prophylaxis in conjunction with lifestyle modifications can decrease frequency and severity of symptoms and include tricyclic antidepressants, calcium channel blockers, anti‐epileptic medications, selective serotonin reuptake inhibitors, serotonin‐norepinephrine reuptake inhibitors, beta‐blockers, gepants, and monoclonal antibodies to CGRP. Promising evidence is emerging regarding the ability of migraine medications to positively treat the various otologic symptoms of migraine. Conclusion Migraine disorder manifesting with primarily cochleovestibular symptoms can be challenging to diagnose and manage for practicing clinicians. Patients with various vestibulopathies that are closely related to migraine may benefit from migraine treatment. Lifestyle choices and prophylactic medications are key to satisfactorily preventing acute migrainous attacks and improve function

Decellularized Human Cornea for Reconstructing the Corneal Epithelium and Anterior Stroma

In this project, we strived to develop a decellularized human cornea to use as a scaffold for reconstructing the corneal epithelium and anterior stroma. Human cadaver corneas were decellularized by five different methods, including detergent- and nondetergent-based approaches. The success of each method on the removal of cells from the cornea was investigated. The structural integrity of decellularized corneas was compared with the native cornea by electron microscopy. The integrity of the basement membrane of the epithelium was analyzed by histology and by the expression of collagen type IV, laminin, and fibronectin. Finally, the ability of the decellularized corneas to support the growth of human corneal epithelial cells and fibroblasts was assessed in vitro. Corneas processed using Triton X-100, liquid nitrogen, and poly(ethylene glycol) resulted in incomplete removal of cellular material. Corneas processed with the use of sodium dodecyl sulfate (SDS) or with sodium chloride (NaCl) plus nucleases successfully removed all cellular material; however, only the NaCl plus nuclease treatment kept the epithelial basement membrane completely intact. Corneas processed with NaCl plus nuclease supported both fibroblast and epithelial cell growth in vitro, while corneas treated with SDS supported the growth of only fibroblasts and not epithelial cells. Decellularized human corneas provide a scaffold that can support the growth of corneal epithelial cells and stromal fibroblasts. This approach may be useful for reconstructing the anterior cornea and limbus using autologous cells

Decellularized Human Cornea for Reconstructing the Corneal Epithelium and Anterior Stroma

In this project, we strived to develop a decellularized human cornea to use as a scaffold for reconstructing the corneal epithelium and anterior stroma. Human cadaver corneas were decellularized by five different methods, including detergent- and nondetergent-based approaches. The success of each method on the removal of cells from the cornea was investigated. The structural integrity of decellularized corneas was compared with the native cornea by electron microscopy. The integrity of the basement membrane of the epithelium was analyzed by histology and by the expression of collagen type IV, laminin, and fibronectin. Finally, the ability of the decellularized corneas to support the growth of human corneal epithelial cells and fibroblasts was assessed in vitro. Corneas processed using Triton X-100, liquid nitrogen, and poly(ethylene glycol) resulted in incomplete removal of cellular material. Corneas processed with the use of sodium dodecyl sulfate (SDS) or with sodium chloride (NaCl) plus nucleases successfully removed all cellular material; however, only the NaCl plus nuclease treatment kept the epithelial basement membrane completely intact. Corneas processed with NaCl plus nuclease supported both fibroblast and epithelial cell growth in vitro, while corneas treated with SDS supported the growth of only fibroblasts and not epithelial cells. Decellularized human corneas provide a scaffold that can support the growth of corneal epithelial cells and stromal fibroblasts. This approach may be useful for reconstructing the anterior cornea and limbus using autologous cells

Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.

ObjectiveTo determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS).Study designProspective study.SettingSingle institution, academic tertiary care lateral skull base surgery program.PatientsPatients diagnosed with VS.InterventionsA comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool.Main outcome measuresPre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared.ResultsA pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p &lt; 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction.ConclusionsImplementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future

Peripheral Ulcerative Keratitis: A Review

Peripheral ulcerative keratitis (PUK) is a rare but serious ocular condition that is an important clinical entity due to its ophthalmological and systemic implications. It is characterized by progressive peripheral corneal stromal thinning with an associated epithelial defect and can be associated with an underlying local or systemic pro-inflammatory condition, or present in an idiopathic form (Mooren ulcer). Associated conditions include autoimmune diseases, systemic and ocular infections, dermatologic diseases, and ocular surgery. Cell-mediated and autoantibody- mediated immune responses have been implicated in the pathogenesis of PUK, destroying peripheral corneal tissue via matrix metalloproteinases. Clinically, patients with PUK present with painful vision loss, a peripheral corneal ulcer, and often adjacent scleritis, episcleritis, iritis, or conjunctivitis. Diagnostic evaluation should be focused on identifying the underlying etiology and ruling out conditions that may mimic PUK, including marginal keratitis and Terrien marginal degeneration. Treatment should be focused on reducing local disease burden with topical lubrication, while simultaneously addressing the underlying cause with antimicrobials or anti-inflammatory when appropriate. Existing and emerging biologic immunomodulatory therapies have proven useful in PUK due to autoimmune conditions. Surgical treatment is generally reserved for cases of severe thinning or corneal perforation

Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform response

Inflammatory skin disorders result in significant epidermal changes, including keratinocyte hyperproliferation, incomplete differentiation, and impaired barrier. Here we test whether, conversely, an impaired epidermal barrier can promote an inflammatory response. Mice lacking the transcription factor Kruppel-like factor 4 (Klf4) have a severe defect in epidermal barrier acquisition. Transcription profiling of Klf4(–/–) newborn skin revealed similar changes in gene expression to involved psoriatic plaques, including a significant upregulation of the gap junction protein connexin 26 (Cx26). Ectopic expression of Cx26 from the epidermis-specific involucrin (INV) promoter (INV-Cx26) demonstrated that downregulation of Cx26 is required for barrier acquisition during development. In juvenile and adult mice, persistent Cx26 expression kept wounded epidermis in a hyperproliferative state, blocked the transition to remodeling, and led to an infiltration of immune cells. Mechanistically, ectopic expression of Cx26 in keratinocytes resulted in increased ATP release, which delayed epidermal barrier recovery and promoted an inflammatory response in resident immune cells. These results provide a molecular link between barrier acquisition in utero and epidermal remodeling after wounding. More generally, these studies suggest that the most effective treatments for inflammatory skin disorders might concomitantly suppress the immune response and enhance epidermal differentiation to restore the barrier