Exploring cognitive impairment in the early stages of an out-of-hospital cardiac arrest - a consecutive case series study.

Cognitive deficits are common, although often mild, in out-of-hospital cardiac arrest patients. Prevalence and severity of cognitive deficits on discharge from acute hospital, however, are not systematically assessed in clinical practice, and not frequently reported in scientific literature, potentially hindering the development of appropriate follow-up care pathways for these patients. We hereby present data from a consecutive case series of 75 out-of-hospital cardiac arrest patients discharged from our hospital over a period of 16 months; for 46 of them we were able to obtain a cognitive profile around the time of discharge from hospital, with 37 of them experiencing cognitive deficits, ranging from mild to severe. Memory, verbal fluency and cognitive flexibility were the areas more frequently impaired. The patients we were able to assess did not differ for age, cerebral performance category score and time to return of spontaneous circulation from those we were unable to assess. Cognitive deficits were not associated with duration of "no/low blood flow" during cardiac arrest or with age. Our results suggest that cognitive deficits in the immediate aftermath of out-of-hospital cardiac arrest are common; however, these may be missed due to lack of systematic assessment and use of poorly sensitive cognitive tests.

Effect of intravitreal dexamethasone implant in treatment-naive and previously-treated patients with diabetic macular edema.

PURPOSE: To document the effects of intravitreal dexamethasone implant on retinal microvasculature in patients with diabetic retinopathy complicated by center-involving macular edema. METHODS: 35 eyes of 35 patients affected by retinopathy due to type 2 diabetes (15 treatment-naïve and 20 previously treated) were included in this retrospective study with a follow-up of 4 months. Foveal avascular zone (FAZ) area and superficial capillary plexus (SCP) and deep capillary plexus (DCP) densities in the foveal and parafoveal areas were measured by optical coherence tomography angiography (OCTA) at baseline and 2 and 4 months post-injection. Intraocular pressure, morphological and functional parameters were evaluated. RESULTS: a significant difference was found in both groups at 2 months after injection in terms of functional (BCVA, p < 0.05) and morphological (CMT, p < 0.05) parameters. During follow-up, FAZ area, SCP, and DCP in the foveal and parafoveal areas did not change significantly. CONCLUSIONS: intravitreal dexamethasone implant is effective in the treatment of diabetic center-involving macular edema and was associated with significant improvements in BCVA and CMT at 2 months after injection. After a single dexamethasone implant injection, FAZ area and retinal vascular density does not show significant variations in both naive and non-naive DME patients subgroups.

Intrinsic neural stem cell properties define brain hypersensitivity to genotoxic stress.

Impaired replication has been previously linked to growth retardation and microcephaly; however, why the brain is critically affected compared with other organs remains elusive. Here, we report the differential response between early neural progenitors (neuroepithelial cells [NECs]) and fate-committed neural progenitors (NPs) to replication licensing defects. Our results show that, while NPs can tolerate altered expression of licensing factors, NECs undergo excessive replication stress, identified by impaired replication, increased DNA damage, and defective cell-cycle progression, leading eventually to NEC attrition and microcephaly. NECs that possess a short G1 phase license and activate more origins than NPs, by acquiring higher levels of DNA-bound MCMs. In vivo G1 shortening in NPs induces DNA damage upon impaired licensing, suggesting that G1 length correlates with replication stress hypersensitivity. Our findings propose that NECs possess distinct cell-cycle characteristics to ensure fast proliferation, although these inherent features render them susceptible to genotoxic stress.

Follow-up care after out-of-hospital cardiac arrest: A pilot study of survivors and families' experiences and recommendations.

BACKGROUND AND OBJECTIVES: Cognitive and physical difficulties are common in survivors of out-of-hospital cardiac arrest (OHCA); both survivors and close family members are also at risk of developing mood disorders. In the UK, dedicated follow-up pathways for OHCA survivors and their family are lacking. A cohort of survivors and family members were surveyed regarding their experience of post-discharge care and their recommended improvements. METHOD: 123 OHCA survivors and 39 family members completed questionnaires during an educational event or later online. Questions addressed both the actual follow-up offered and the perceived requirements for optimal follow-up from the patient and family perspective, including consideration of timing, professionals involved, involvement of family members and areas they felt should be covered. RESULTS: Outpatient follow-up was commonly arranged after OHCA (77%). This was most often conducted by a cardiologist alone (80%) but survivors suggested that other professionals should also be involved (e.g. psychologist/counsellor, 64%). Topics recommended for consideration included cardiac arrest-related issues (heart disease; cause of arrest) mental fatigue/sleep disturbance, cognitive problems, emotional problems and daily activities. Most survivors advocated an early review (<1month; 61%). Most family members reported some psychological difficulties (95%); many of them (95%) advocated a dedicated follow-up appointment for family members of survivors. CONCLUSIONS: The majority of OHCA survivors advocated an early follow-up following hospital discharge and a holistic, multidimensional assessment of arrest sequelae. These results suggest that current OHCA follow-up often fails to address patient-centred issues and to provide access to professionals deemed important by survivors and family members.

Spontaneous resolution of optic pit maculopathy: an OCT report.

The separation of the vitreous from the optic nerve head and the macula plays a primary role in the spontaneous resolution of optic disc pit (ODP) maculopathy. Optical coherence tomography (OCT) helps in the non-invasive monitoring of this condition, when treated conservatively. The aim of this report was to describe a pediatric case of spontaneously resolved ODP maculopathy, managed conservatively and monitored by means of spectral domain (SD)-OCT. A 14-year-old girl presented with severe visual loss in the right eye (RE). Fundus examination demonstrated a temporal ODP with altered foveal reflex. The SD-OCT B-scans revealed severe intraretinal schisis-like changes, broad vitreal adhesion in the optic nerve head area, posterior hyaloid thickening, and vitreal entrapment in the premacular space. The patient was managed conservatively. Spontaneous resolution of ODP maculopathy took place over 3 months, with vision improved up to 1.0 (Snellen charts). The macular schisis progressively resolved after posterior vitreous detachment. In conclusion, in our report, a complete restoration of the foveal anatomy was achieved without any surgical intervention. This OCT-based report confirms the role of the vitreomacular abnormalities in the pathogenesis of the disease.

Feasibility and Safety of Intraoperative Optical Coherence Tomography-Guided Short-Term Posturing Prescription after Macular Hole Surgery.

PURPOSE: To assess closure rate and visual outcome of a court of patients with macular hole (MH) who underwent surgical repair with intraoperative optical coherence tomography (iOCT)-confirmed MH closure and short-term postoperative face-down posturing (FDP). Secondary aim was to assess the correlation between iOCT and postoperative OCT at day 1. METHODS: Retrospective clinical study conducted in the Miulli Hospital Acquaviva delle Fonti (Italy), enrolling patients with idiopathic MH who underwent 25-G pars plana vitrectomy plus internal limiting membrane peeling. During surgery, closure of MH was confirmed by iOCT and short-term FDP (12-24 h, until day-1 visit) was prescribed. All patients had measurement of best-corrected visual acuity (BCVA) and spectral domain-OCT before the surgery and during follow-up (at 1 day, 1 month, 3 months). RESULTS: Twenty-nine eyes of 29 patients (14 males, 62.1%) were enrolled in the study. MH mean size was 451.7 ± 139.7 µm and baseline BCVA was 0.77 ± 0.26 logarithm of the minimum angle of resolution (LogMAR). MH was confirmed to be closed in 100% of patients intraoperatively (iOCT) and at OCT during early follow-up (1-3 days). Mean time of FDP was 18 ± 2.6 h. At 3 months, MH closure rate was 93%; 2 eyes -underwent secondary MH repair surgery. Final BCVA was 0.39 ± 0.22 LogMAR (p < 0.0001). CONCLUSION: iOCT-based confirmation of MH closure could be a safe and useful tool for prescribing short-term FDP after surgery, with high closure rate and no additional complication. The execution of an OCT in the immediate postoperative days could be potentially unnecessary.

PROGRESSION OF RETINAL ISCHEMIA IN A CASE OF MACULAR TELANGIECTASIA TYPE 1 AFTER RANIBIZUMAB INJECTION: OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS.

PURPOSE: To describe a case of a 68-year-old man with macular telangiectasia (MacTel) Type 1 in the right eye, showing an increase in capillary ischemia after intravitreal ranibizumab. METHODS: The patient underwent complete ophthalmologic evaluation, including best-corrected visual acuity, intraocular pressure, anterior segment and fundus examination, optical coherence tomography (OCT), and OCT angiography at baseline and on each visit. Fluorescein angiography was performed at baseline. The patient was followed up on monthly bases for 22 months. RESULTS: The patient presented a best-corrected visual acuity of 20/80 in the right eye and of 20/25 in the left eye at baseline. In the right eye, the fluorescein angiography images showed perifoveal capillary ectasia, late-frames dye leakage, and enlargement of the foveal avascular zone. The OCT showed intraretinal pseudocysts and microaneurysms, and the OCT angiography showed vascular rarefaction, capillary dropout, and capillary ectasia of the superficial plexus. After 16 months of follow-up and four ranibizumab injections, the best-corrected visual acuity was 20/60, and the OCT angiography disclosed a further enlargement of the foveal avascular zone area and increased capillary obliteration in the perifoveal nasal area. CONCLUSION: Optical coherence tomography angiography may represent an indispensable diagnostic technique, complementary to traditional imaging, in the evaluation of the effects of anti-vascular endothelial growth factor therapy in patients with MacTel Type 1.

Panretinal Photocoagulation Does Not Change Macular Perfusion in Eyes With Proliferative Diabetic Retinopathy.

BACKGROUND AND OBJECTIVE: To quantify and compare the vessel density (VD) in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP), as well as the size of the foveal avascular zone (FAZ) in patients with proliferative diabetic retinopathy (PDR) before and after panretinal photocoagulation (PRP). PATIENTS AND METHODS: This prospective clinical study was conducted in the Department of Ophthalmology, Miulli Hospital Acquaviva delle Fonti, Italy. Each patient underwent measurement of best-corrected visual acuity (BCVA), fluorescein angiography, spectral-domain optical coherence tomography (OCT), and OCT angiography (OCTA) at baseline. Patients received PRP within 7 days from baseline, using frequency-doubled Nd:YAG pattern scan laser. BCVA and OCTA were repeated at 1 month and at 6 months. Repeated measure one-way analysis of variance was used to investigate differences between OCTA parameters before and after PRP. RESULTS: Eighteen eyes of 14 patients with diabetes (11 males, 78.6%) were enrolled. Patients underwent a mean of four laser treatments. BCVA was slightly worse at baseline (0.30 ± 0.20) compared to the visual function after 6 months (0.25 ± 0.24; P = .3). FAZ (0.33 ± 0.19 mm2 vs. 0.33 ± 0.16 mm2; P = .6), foveal SCP (16.4 ± 8.0 vs. 16.5 ± 6.5; P = .4), foveal DCP (28.5 ± 8.6 vs. 28.2 ± 8.1; P = .8), parafoveal SCP (38.4 ± 5.7 vs. 38.6 ± 4.5; P = .9), and parafoveal DCP (46.1 ± 5.2 vs. 43.8 ± 5.1; P = .3) did not change 6 months after PRP. CONCLUSIONS: OCTA parameters were not significantly affected by peripheral laser treatment at both short- (1-month) and medium- / long-term (6-month) follow-up. Further analysis with larger samples and longer duration is warranted to confirm these results. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:174-178.].

Optical Coherence Tomography Angiography Evolution of Choroidal Neovascular Membrane in Choroidal Rupture Managed by Intravitreal Bevacizumab.

PURPOSE: To describe a case of a 25-year-old man with choroidal neovascularization (CNV) secondary to traumatic choroidal rupture treated with intravitreal bevacizumab and to evaluate the vascular structure of the area near the traumatic choroidal rupture. METHODS: The patient underwent complete ophthalmologic evaluation, including best-corrected visual acuity (BCVA), intraocular pressure, anterior segment and funds examination, and optical coherence tomography angiography (OCTA) at baseline and on each follow-up visit. Fluorescein angiography (FA) was performed at baseline. Intravitreal bevacizumab was administered at the time of choroidal neovascular membrane diagnosis. RESULTS: At baseline, ophthalmoscopic examination of the left eye revealed four subretinal macular hemorrhages and two choroidal ruptures located temporally to the fovea. On OCT angiograms, the choroidal rupture appeared as a hypointense break in choriocapillaris plexus. At 4-week follow-up, the OCTA disclosed a well circumscribed lesion characterized by numerous and fine anastomotic vessels. Patient received intravitreal injection of bevacizumab. At 6-week post injection, OCTA documented regression of the neovascular complex. CONCLUSION: Choroidal neovascularization is a common complication associated with traumatic choroidal rupture and OCTA may represent a complementary diagnostic technique to evaluate the vascular structure of the area near the traumatic choroidal rupture.

Extracranial Internal Carotid Artery Aneurysm in a Patient with Marfan Syndrome.

Extracranial internal carotid artery (ICA) aneurysms are rare and most of them are considered of atherosclerotic etiology. Marfan syndrome (MS) is a systemic connective tissue disorder caused by mutation in the extracellular matrix protein fibrillin 1. Clinical manifestations of the MS include aortic aneurysms, dislocation of the ocular lens, and long bone overgrowth. The presence of extracranial ICA aneurysm in patients with MS is very rare. We report a 62-year-old female patient with MS presented with an extracranial ICA aneurysm. She was treated with aneurysmectomy and end-to-end anastomosis, with good outcomes. Only 10 cases of patients with MS and extracranial ICA aneurysm have been described in the literature. Clinical presentation, treatment, and outcome of these patients are reviewed and discussed.

Optical Coherence Tomography Angiography versus Dye Angiography in Age-Related Macular Degeneration: Sensitivity and Specificity Analysis.

INTRODUCTION: Optical coherence tomography angiography (OCTA) could be a valid tool to detect choroidal neovascularization (CNV) in neovascular age-related macular degeneration (nAMD), allowing the analysis of the type, the morphology, and the extension of CNV in most of the cases. PURPOSE: To determine the sensitivity and specificity of OCTA in detecting CNV secondary to nAMD, compared to fluorescein angiography (FA) and indocyanine green angiography (ICGA). METHODS: Prospective observational study. Patients with suspected nAMD were recruited between May and December 2016. Patients underwent FA, ICGA, spectral domain OCT, and OCTA (AngioVue, Optovue, Inc.). Sensitivity and specificity of FA, with or without ICGA, were assessed and compared with OCTA. RESULTS: Seventy eyes of 70 consecutive patients were included: 32 eyes (45.7%) with type I CNV, 8 eyes (11.4%) with type II CNV, 4 eyes (5.7%) with type III CNV, 6 eyes (8.6%) with mixed type I and type II CNV, and 20 eyes (28.6%) with no CNV. Sensitivity of OCTA was 88% and specificity was 90%. Concordance between FA/ICGA and OCTA was very good (0,91; range 0,81-1,00). CONCLUSIONS: OCTA showed high sensitivity and specificity for detection of CNV. Concordance between OCTA and gold-standard dye-based techniques was excellent. OCTA may represent a first-line noninvasive method for the diagnosis of nAMD.

Hypoxia inducible factor as a therapeutic target for atherosclerosis.

Atherosclerosis is a highly prevalent disease that can significantly increase the risk of major vascular events, such as myocardial or cerebral infarctions. The anoxemia theory states that a disparity between oxygen supply and demand contributes to atherosclerosis. Hypoxia inducible factor-1 (HIF-1) is a heterodimeric protein, part of the basic helix-loop-helix family and one of the main regulators of cellular responses in a low­oxygen environment. It plays a key role in the development of atherosclerosis through cell-specific responses, acting on endothelial cells, vascular smooth muscle cells (SMCs) and macrophages. Through the upregulation of VEGF, NO, ROS and PDGF, HIF-1 is able to cause endothelial cell dysfunction, proliferation, angiogenesis and inflammation. Activation of the NF-kB pathway in endothelial cells is an important contributor to inflammation and positively feedbacks to HIF-1. HIF-1 also plays a significant role in both the proliferation and migration of smooth muscle cells - two important features of atherosclerosis, while the formation of foam cells (lipid-laden macrophages) is also a critical step in atherosclerosis and mediated by HIF-1 through various mechanisms such as dysfunctional efflux pathways in macrophages. Overall, HIF-1 exerts its effect on the pathogenesis of atherosclerosis via a variety of molecular and cellular events in the process. In this review article, we examine the effects HIF-1 on vascular cells and macrophages in the development of atherosclerosis, highlighting the environmental cues and signalling pathways that control HIF-1 expression/activation within the vasculature. We will highlight the potential of HIF-1 as a therapeutic target on the disease development.