Bilateral optic neuritis in a 26-year-old man with common variable immunodeficiency: a case report

<p>Abstract</p> <p>Introduction</p> <p>Common variable immunodeficiency encompasses a group of heterogeneous conditions linked by a lack of immunoglobulin production and primary antibody failure. Although primary immunodeficiencies are typically characterized by recurrent infections, autoimmune manifestations have increasingly been recognized. Neurological complications are extremely rare and to the best of our knowledge optic neuritis has not been described previously. We report the case of a patient with common variable immunodeficiency who developed loss of vision secondary to bilateral optic neuritis.</p> <p>Case presentation</p> <p>A 26-year-old Caucasian man with a diagnosis of common variable immunodeficiency presented to our facility with loss of vision secondary to bilateral optic neuritis. Results of a thorough study for infectious, neoplastic and autoimmune diseases were negative. Our patient was treated with intravenous methylprednisolone with almost complete improvement and he remained asymptomatic at a 12-month follow-up.</p> <p>Conclusions</p> <p>Bilateral optic neuritis should be added to the list of autoimmune disorders related to common variable immunodeficiency. If a patient with common variable immunodeficiency experiences loss of vision, the possibility of bilateral optic neuritis should be considered as rapid initiation of high-dose corticosteroids may improve visual recovery.</p

PRIMA subretinal wireless photovoltaic microchip implantation in non-human primate and feline models

PURPOSE: To evaluate the surgical technique for subretinal implantation of two sizes of PRIMA photovoltaic wireless microchip in two animal models, and refine these surgical procedures for human trials. METHODS: Cats and Macaca fascicularis primates with healthy retina underwent vitrectomy surgery and were implanted with subretinal wireless photovoltaic microchip at the macula/central retina. The 1.5mm PRIMA chip was initially studied in feline eyes. PRIMA implant (2mm,1.5mm sizes) arrays were studied in primates. Feasibility of subretinal chip implantation was evaluated with a newly-developed surgical technique, with surgical complications and adverse events recorded. RESULTS: The 1.5mm implant was placed in the central retina of 11 feline eyes, with implantation duration 43-106 days. The 1.5mm implant was correctly positioned into central macula of 11 primate eyes, with follow-up periods of minimum 6 weeks (n = 11), 2 years (n = 2), and one eye for 3 years. One primate eye underwent multi-chip 1.5mm implantation using two 1.5mm chips. The 2mm implant was delivered to 4 primate eyes. Optical coherence tomography confirmed correct surgical placement of photovoltaic arrays in the subretinal space in all 26 eyes. Intraoperative complications in primate eyes included retinal tear, macular hole, retinal detachment, and vitreous hemorrhage that resolved spontaneously. Postoperatively, there was no case of significant ocular inflammation in the 1.5mm implant group. CONCLUSIONS: We report subretinal implantation of 1.5mm and 2mm photovoltaic arrays in the central retina of feline and central macula of primate eyes with a low rate of device-related complications. The in vivo PRIMA implantation technique has been developed and refined for use for a 2mm PRIMA implant in ongoing human trials

The effect of a preoperative subconjuntival injection of dexamethasone on blood–retinal barrier breakdown following scleral buckling retinal detachment surgery: a prospective randomized placebo-controlled double blind clinical trial

textabstractBackground: Blood-retinal barrier breakdown secondary to retinal detachment and retinal detachment repair is a factor in the pathogenesis of proliferative vitreoretinopathy (PVR). We wished to investigate whether an estimated 700 to 1000 ng/ml subretinal dexamethasone concentration at the time of surgery would decrease the blood-retinal barrier breakdown postoperatively. Methods: Prospective, placebo-controlled, double blind clinical trial. In 34 patients with rhegmatogenous retinal detachment scheduled for conventional scleral buckling retinal detachment surgery, a subconjunctival injection of 0.5 ml dexamethasone diphosphate (10 mg) or 0.5 ml placebo was given 5-6 hours before surgery. Differences in laser flare photometry (KOWA) measurements taken 1, 3 and 6 weeks after randomisation between dexamethasone and placebo were analysed using mixed model ANOVA, while correcting for the preoperative flare measurement. Results: Six patients did not complete the study, one because of recurrent detachment within 1 week, and five because they missed their postoperative laser flare visits. The use of dexamethasone resulted in a statistically significant decrease in laser flare measurements at the 1-week postoperative visit. Conclusion: The use of a preoperative subconjunctival injection of dexamethasone decreased 1-week postoperative blood-retina barrier breakdown in patients undergoing conventional scleral buckling retinal detachment surgery. This steroid priming could be useful as a part of a peri-operative regime that would aim at decreasing the incidence of PVR

Angiopoietin-1 Treatment Reduces Inflammation but Does Not Prevent Ventilator-Induced Lung Injury

Background: Loss of integrity of the epithelial and endothelial barriers is thought to be a prominent feature of ventilator-induced lung injury (VILI). Based on its function in vascular integrity, we hypothesize that the angiopoietin (Ang)-Tie2 system plays a role in the development of VILI. The present study was designed to examine the effects of mechanical ventilation on the Ang-Tie2 system in lung tissue. Moreover, we evaluated whether treatment with Ang-1, a Tie2 receptor agonist, protects against inflammation, vascular leakage and impaired gas exchange induced by mechanical ventilation. Methods: Mice were anesthetized, tracheotomized and mechanically ventilated for 5 hours with either an inspiratory pressure of 10 cmH(2)O ('low' tidal volume similar to 7.5 ml/kg; LVT) or 18 cmH(2)O ('high' tidal volume similar to 15 ml/kg; HVT). At initiation of HVT-ventilation, recombinant human Ang-1 was intravenously administered (1 or 4 mu g per animal). Non-ventilated mice served as controls. Results: HVT-ventilation influenced the Ang-Tie2 system in lungs of healthy mice since Ang-1, Ang-2 and Tie2 mRNA were decreased. Treatment with Ang-1 increased Akt-phosphorylation indicating Tie2 signaling. Ang-1 treatment reduced infiltration of granulocytes and expression of keratinocyte-derived chemokine (KC), macrophage inflammatory protein (MIP)-2, monocyte chemotactic protein (MCP)-1 and interleukin (IL)-1 beta caused by HVT-ventilation. Importantly, Ang-1 treatment did not prevent vascular leakage and impaired gas exchange in HVT-ventilated mice despite inhibition of inflammation, vascular endothelial growth factor (VEGF) and Ang-2 expression. Conclusions: Ang-1 treatment downregulates pulmonary inflammation, VEGF and Ang-2 expression but does not protect against vascular leakage and impaired gas exchange induced by HVT-ventilatio

Contemporary review of risk-stratified management in acute uncomplicated and complicated diverticulitis

BACKGROUND: Acute colonic diverticulitis is a common clinical condition. Severity of the disease is based on clinical, laboratory, and radiological investigations and dictates the need for medical or surgical intervention. Recent clinical trials have improved the understanding of the natural history of the disease resulting in new approaches to and better evidence for the management of acute diverticulitis. METHODS: We searched the Cochrane Library (years 2004-2015), MEDLINE (years 2004-2015), and EMBASE (years 2004-2015) databases. We used the search terms "diverticulitis, colonic" or "acute diverticulitis" or "divertic*" in combination with the terms "management," "antibiotics," "non-operative," or "surgery." Registers for clinical trials (such as the WHO registry and the https://clinicaltrials.gov/) were searched for ongoing, recruiting, or closed trials not yet published. RESULTS: Antibiotic treatment can be avoided in simple, non-complicated diverticulitis and outpatient management is safe. The management of complicated disease, ranging from a localized abscess to perforation with diffuse peritonitis, has changed towards either percutaneous or minimally invasive approaches in selected cases. The role of laparoscopic lavage without resection in perforated non-fecal diverticulitis is still debated; however, recent evidence from two randomised controlled trials has found a higher re-intervention in this group of patients. CONCLUSIONS: A shift in management has occurred towards conservative management in acute uncomplicated disease. Those with uncomplicated acute diverticulitis may be treated without antibiotics. For complicated diverticulitis with purulent peritonitis, the use of peritoneal lavage appears to be non-superior to resection

The Rotterdam Study: objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in the Netherlands. The study targets cardiovascular, neurological, ophthalmological and endocrine diseases. As of 2008 about 15,000 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in some 600 research articles and reports (see http://www.epib.nl/rotterdamstudy). This article gives the reasons for the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Decreased surfactant phosphatidylcholine synthesis in neonates with congenital diaphragmatic hernia during extracorporeal membrane oxygenation

Purpose: Congenital diaphragmatic hernia (CDH) may result in severe respiratory insufficiency with a high morbidity. The role of a disturbed surfactant metabolism in the pathogenesis of CDH is unclear. We therefore studied endogenous surfactant metabolism in the most severe CDH patients who required extracorporeal membrane oxygenation (ECMO). Methods: Eleven neonates with CDH who required ECMO and ten ventilated neonates without significant lung disease received a 24-h infusion of the stable isotope [U-13C] glucose. The13C-incorporation into palmitic acid in surfactant phosphatidylcholine (PC) isolated from serial tracheal aspirates was measured. Mean PC concentration in epithelial lining fluid (ELF) was measured during the first 4 days of the study. Results: Fractional surfactant PC synthesis was decreased in CDH-ECMO patients compared to controls (2.4 ± 0.33 vs. 8.0 ± 2.4%/day, p = 0.04). The control group had a higher maximal enrichment (0.18 ± 0.03 vs. 0.09 ± 0.02 APE, p = 0.04) and reached this maximal enrichment earlier (46.7 ± 3.0 vs. 69.4 ± 6.6 h, p = 0.004) compared to the CDH-ECMO group, which reflects higher and faster precursor incorporation in the control group. Surfactant PC concentration in ELF was similar in both groups. Conclusion: These results show that CDH patients who require ECMO have a decreased surfactant PC synthesis, which may be part of the pathogenesis of severe pulmonary insufficiency and has a negative impact on weaning from ECMO

Promises of stem cell therapy for retinal degenerative diseases

With the development of stem cell technology, stem cell-based therapy for retinal degeneration has been proposed to restore the visual function. Many animal studies and some clinical trials have shown encouraging results of stem cell-based therapy in retinal degenerative diseases. While stem cell-based therapy is a promising strategy to replace damaged retinal cells and ultimately cure retinal degeneration, there are several important challenges which need to be overcome before stem cell technology can be applied widely in clinical settings. In this review, different types of donor cell origins used in retinal treatments, potential target cell types for therapy, methods of stem cell delivery to the eye, assessments of potential risks in stem cell therapy, as well as future developments of retinal stem cells therapy, will be discussed