Hierarchical Surface Pattern on Ni-Free Ti-Based Bulk Metallic Glass to Control Cell Interactions.

Ni-free Ti-based bulk metallic glasses (BMGs) are exciting materials for biomedical applications because of their outstanding biocompatibility and advantageous mechanical properties. The glassy nature of BMGs allows them to be shaped and patterned via thermoplastic forming (TPF). This work demonstrates the versatility of the TPF technique to create micro- and nano-patterns and hierarchical structures on Ti40Zr10Cu34Pd14Sn2 BMG. Particularly, a hierarchical structure fabricated by a two-step TPF process integrates 400 nm hexagonal close-packed protrusions on 2.5 µm square protuberances while preserving the advantageous mechanical properties from the as-cast material state. The correlations between thermal history, structure, and mechanical properties are explored. Regarding biocompatibility, Ti40Zr10Cu34Pd14Sn2 BMGs with four surface topographies (flat, micro-patterned, nano-patterned, and hierarchical-structured surfaces) are investigated using Saos-2 cell lines. Alamar Blue assay and live/dead analysis show that all tested surfaces have good cell proliferation and viability. Patterned surfaces are observed to promote the formation of longer filopodia on the edge of the cytoskeleton, leading to star-shaped and dendritic cell morphologies compared with the flat surface. In addition to potential implant applications, TPF-patterned Ti-BMGs enable a high level of order and design flexibility on the surface topography, expanding the available toolbox for studying cell behavior on rigid and ordered surfaces.

Mini-Open Fascia Lata Interposition Graft Results In Superior 2-Year Clinical Outcomes When Compared to Arthroscopic Partial Repair for Irreparable Rotator Cuff Tear: A Single-Blind Randomized Controlled Trial.

PURPOSE: To evaluate and compare the results of surgical treatment for irreparable rotator cuff tear (IRCT) by the mini-open interposition procedure using fascia lata autograft against outcomes of the arthroscopic partial repair technique. METHODS: An interventional, prospective, controlled, randomized, single-blinded study involving 2 study groups was conducted. The graft group (n = 20) underwent the mini-open interposition procedure using fascia lata autograft. The control group (n = 22) underwent arthroscopic partial repair. Patients were evaluated using the University of California Los Angeles (UCLA) Shoulder scale, the American Shoulder and Elbow Surgeons (ASES) score, the Constant-Murley (Constant) score, the visual analogue scale (VAS) pain score, active range of motion, frontal flexion strength, retear rates evaluated by magnetic resonance imaging analysis, occurrence of complications, and the minimal clinically important difference (MCID). RESULTS: The graft group had better UCLA (31.5 vs 28.18, P = .035) (100% exceeded the MCID for the graft group and 95% for the control group), ASES (88.62 vs 77.06, P = .016) (100% exceeded the MCID for both groups), Constant (78.85 vs 61.68, P < .001), and VAS (0.95 vs 2.59, P = .01) scores at the 24-month follow-up. For active forward elevation range, both groups showed no statistically significant differences (168.5 vs 164.54, P = .538). The results for active external and internal rotation were better in the graft group (60.25 vs 40, and 9.1 vs 6.9, P < .001), as was frontal flexion strength (4.24 vs 2.67, P = .005). The graft group also had lower retear rates (15% vs 45.5%, P = .033). No complications were reported. CONCLUSIONS: Outcomes of surgeries for IRCT by the mini-open interposition procedure using fascia lata autograft and by the arthroscopic partial repair technique showed good results in both groups over time and exceeded the MCID. However, most comparative outcomes between groups showed better results for the interposition procedure. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Anatomical study of the safety corridor for bridge plating positioned on the lateral border of the humerus.

PURPOSE: This study shows the danger zone and the safety corridor in the lateral approach with bridge plating by measuring the distance between the lateral side of the plate positioned on the lateral aspect of the humerus and the radial nerve after it pierces the lateral intermuscular septum, in the different forearm positions. METHODS: Forty arms of 20 human cadavers were used, the radial nerve was identified and marked on the lateral surface the radial nerve at the exit of the lateral intermuscular septum and anteriorisation of the nerve in relation to the humeral shaft and the lateral epicondyle was also marked. The distances were measured with a digital caliper. A submuscular extraperiosteal corridor was created, proximally between the biceps brachialis and deltoid muscle and distally between the triceps and brachioradialis muscle, followed by the positioning of the low contact large fragments contoured plate with 14 combined holes (fixed and cortical angle), inserted from distal to proximal. Measurements were performed in four positions (elbow flexion with forearm pronation, elbow flexion with forearm supination, elbow extension with forearm pronation and elbow extension with forearm supination). RESULTS: Significant statistical differences occurred with the different positions, and the elbow flexion with forearm supination was shown to be the position that provides the safest submuscular extraperiosteal corridor in a lateral approach of the humerus. CONCLUSION: The danger zone of radial nerve is an area that extends from 15 cm to 5 cm proximal to the lateral epicondyle and the safest way to create a submuscular and extraperiosteal corridor in the lateral region of the humerus is with the elbow in flexion and the forearm in supination.

Silencing of heat shock factor 1 (HSF1) inhibits proliferation, invasion, and epithelial-mesenchymal transition in oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma is characterized by high rates of morbidity and mortality. Evidence obtained for different types of cancer shows that tumor initiation, progression, and therapeutic resistance are regulated by heat shock factor 1. This research aimed to analyze the effects of heat shock factor 1 on the biological behavior of oral squamous cell carcinoma. METHODS: Clinicopathological and immunoexpression study of heat shock factor 1 in 70 cases of oral tongue SCC and functional assays by gene silencing of this factor in an oral tongue SCC cell line. RESULTS: Heat shock factor 1 was overexpressed in oral tongue SCC specimens compared to normal oral mucosa (p < 0.0001) and in the SCC15 line compared to immortalized keratinocytes (p < 0.005). No significant associations were observed between overexpression of heat shock factor 1 and clinicopathological parameters or survival rates of the oral tongue SCC cases in the present sample. In vitro experiments showed that heat shock factor 1 silencing inhibited cell proliferation (p < 0.005) and cell cycle progression, with the accumulation of cells in the G0/G1 phase (p < 0.01). In addition, heat shock factor 1 silencing reduced cell invasion capacity (p < 0.05) and epithelial-mesenchymal transition, characterized by a decrease in vimentin expression (p < 0.05) and an increase in E-cadherin expression (p < 0.001). CONCLUSION: Heat shock factor 1 may exert several functions that help maintain cell stability under the stressful conditions of the tumor microenvironment. Thus, strategies targeting the regulation of this protein may in the future be a useful therapeutic tool to control the progression of oral squamous cell carcinoma.

Giant benign lymphangioendothelioma with positive expression of Wilms tumor 1: A case report.

Benign lymphangioendothelioma (BL, acquired progressive lymphangioma) is a rare, slow-growing lymphatic tumor, first described 40 years ago, with fewer than 50 published cases. Clinically, it presents as a skin-colored or erythematous patch. Definitive diagnosis requires histopathological examination. The immunohistochemical staining profile is still controversial regarding Wilms tumor 1 (WT1) expression, a marker of proliferative and neoplastic, rather than malformative nature. Here, we report a case of a 60-cm-long BL on the breast of an adult female. Biopsy revealed irregular vascular spaces dissecting the collagen bundles lined by swollen endothelial cells but without cellular atypia. Positivity for podoplanin (D2-40), CD31, and WT1 was observed, supporting the neoplastic nature of this lesion. Dermatologists and pathologists must be aware of this entity for early diagnosis and treatment.

Histopathologic grading and its relationship with outcome in oral tongue squamous cell carcinoma.

BACKGROUND: Histopathologic grading has been routinely used as a complement for clinical staging in the prognostication of patients with oral tongue squamous cell carcinoma (OTSCC). However, this subject remains contentious because there is no universally accepted grading system. OBJECTIVES: This study compared the prognostic significance of four histopathologic grading systems in 80 cases of oral tongue squamous cell carcinoma (OTSCC). METHODS: Clinical and follow-up information of the patients were obtained from medical records. Histopathologic malignancy grading of the tumor invasive front, Histologic risk assessment (HRA), World Health Organization (WHO) grading system, and Budding and Depth of invasion (BD) model were evaluated in the surgical specimens. RESULTS: The HRA, histopathologic malignancy grading and WHO systems did not predict survival. Patients with larger tumor size [Hazard ratio (HR): 2.38; 95% confidence interval (CI): 1.07-5.27; P = 0.026] and patients with BD model high-grade tumors (HR: 2.99; 95% CI: 1.03-8.68; P = 0.034) were significantly associated with a poor 5-year overall survival rate. In the multivariate analysis, tumor size was identified as the only significant independent prognostic factor (HR: 2.23; 95% CI: 1.00-4.99; P = 0.050). None of the grading systems studied was associated with 5-year disease-free survival rates. CONCLUSIONS: BD model was the only histopathologic grading system associated with the outcome of patients with OTSCC, indicating its potential value as an effective tool for the prognostication of OTSCC.

Peripheral compound odontoma: A rare case report and literature review.

Peripheral odontoma is a very rare odontogenic hamartoma arising in soft tissues. Here, we report a case of peripheral odontoma in a pediatric patient and review the cases published in the literature. An 11-year-old male patient presented a nodular lesion in the anterior region of the palate for over 1 year. Under the clinical hypothesis of fibroma, an excisional biopsy was performed. Histopathological examination revealed the presence of tooth-like structures, formed by enamel, and dentin matrix, occasionally associated with the dental papilla and surrounding pulp tissue, thus, the histopathological diagnosis of peripheral odontoma was established. The patient has been undergoing follow-up for 6 months without any signs of lesion recurrence. Peripheral odontomas are uncommon lesions that usually affect young patients and display a preference for the maxilla and limited growth potential. The recognition of the clinical and histopathological features of the peripheral odontoma is indispensable for the establishment of its diagnosis.

Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration: Evidence from the EYE-RISK and European Eye Epidemiology Consortia.

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and high-density lipoproteins (HDLs) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relationship to AMD in a large European dataset. DESIGN: Pooled analysis of cross-sectional data. PARTICIPANTS: Individuals (N = 30 953) aged 50 years or older participating in the European Eye Epidemiology (E3) consortium and 1530 individuals from the Rotterdam Study with lipid subfraction data. METHODS: AMD features were graded on fundus photographs using the Rotterdam classification. Routine blood lipid measurements, genetics, medication, and potential confounders were extracted from the E3 database. In a subgroup of the Rotterdam Study, lipid subfractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random effect were used to estimate associations. MAIN OUTCOME MEASURES: AMD features and stage; lipid measurements. RESULTS: HDL was associated with an increased risk of AMD (odds ratio [OR], 1.21 per 1-mmol/l increase; 95% confidence interval [CI], 1.14-1.29), whereas triglycerides were associated with a decreased risk (OR, 0.94 per 1-mmol/l increase; 95% CI, 0.91-0.97). Both were associated with drusen size. Higher HDL raised the odds of larger drusen, whereas higher triglycerides decreases the odds. LDL cholesterol reached statistical significance only in the association with early AMD (P = 0.045). Regarding lipid subfractions, the concentration of extra-large HDL particles showed the most prominent association with AMD (OR, 1.24; 95% CI, 1.10-1.40). The cholesteryl ester transfer protein risk variant (rs17231506) for AMD was in line with increased HDL levels (P = 7.7 × 10-7), but lipase C risk variants (rs2043085, rs2070895) were associated in an opposite way (P = 1.0 × 10-6 and P = 1.6 × 10-4). CONCLUSIONS: Our study suggested that HDL cholesterol is associated with increased risk of AMD and that triglycerides are negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL subfractions seem to be drivers in the relationship with AMD, and variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains to be answered.

OPTICAL COHERENCE TOMOGRAPHY BASELINE PREDICTORS FOR INITIAL BEST-CORRECTED VISUAL ACUITY RESPONSE TO INTRAVITREAL ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT IN EYES WITH DIABETIC MACULAR EDEMA: The CHARTRES Study.

PURPOSE: To identify baseline optical coherence tomography morphologic characteristics predicting the visual response to anti-vascular endothelial growth factor therapy in diabetic macular edema. METHODS: Sixty-seven patients with diabetic macular edema completed a prospective, observational study (NCT01947881-CHARTRES). All patients received monthly intravitreal injections of Lucentis for 3 months followed by PRN treatment and underwent best-corrected visual acuity measurements and spectral domain optical coherence tomography at Baseline, Months 1, 2, 3, and 6. Visual treatment response was characterized as good (≥10 letters), moderate (5-10 letters), and poor (<5 or letters loss). Spectral domain optical coherence tomography images were graded before and after treatment by a certified Reading Center. RESULTS: One month after loading dose, 26 patients (38.80%) were identified as good responders, 19 (28.35%) as Moderate and 22 (32.83%) as poor responders. There were no significant best-corrected visual acuity and central retinal thickness differences at baseline (P = 0.176; P = 0.573, respectively). Ellipsoid zone disruption and disorganization of retinal inner layers were good predictors for treatment response, representing a significant risk for poor visual recovery to anti-vascular endothelial growth factor therapy (odds ratio = 10.96; P < 0.001 for ellipsoid zone disruption and odds ratio = 7.05; P = 0.034 for disorganization of retinal inner layers). CONCLUSION: Damage of ellipsoid zone, higher values of disorganization of retinal inner layers, and central retinal thickness decrease are good predictors of best-corrected visual acuity response to anti-vascular endothelial growth factor therapy.

Cripto-1 is overexpressed in carcinoma ex pleomorphic adenoma of salivary gland.

INTRODUCTION: Cripto-1 is a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family. Besides being critical for early embryonic development, Cripto-1 is also associated with the development and behavior of several cancers. OBJECTIVE: We analyzed the immunoexpression of Cripto-1 in normal salivary glands (NSGs), pleomorphic adenomas (PAs), and carcinoma ex pleomorphic adenomas (CaExPAs) of salivary glands. METHODS: A total of 12 NSGs, 16 PAs and 12 CaExPAs underwent immunohistochemical study by the polymeric biotin-free technique. Immunopositive cells were evaluated semiquantitatively (scores 0-3). For statistical analysis, Mann-Whitney and Kruskal-Wallis tests were performed and a significance level of p ≤ 0.05 was established. RESULTS: Most CaExPAs (n = 10) were strong positive (score 3) for Cripto-1, and only three cases of PAs and two specimens of NSGs exhibited some expression (score 1), being statistically significant these findings (p < 0.001). No difference between the expression of this protein in tumors of major and minor salivary glands was observed. Overexpression was found mainly in cases of CaExPAs with invasive growth (n = 8) when compared to those without capsular invasion (intracapsular pattern) (p = 0.036). Patients with or without lymph node metastasis showed no difference (p = 0.294). CONCLUSION: The results revealed a significantly higher expression of Cripto-1 in CaExPA compared to PA and NSG, suggesting this protein is possibly deregulated in PA malignant transformation. Furthermore, the increased expression of this protein is associated with a more aggressive behavior (invasive growth) in salivary gland tumors.

Development of a Normative Database for Multifocal Electroretinography in the Context of a Multicenter Clinical Trial.

PURPOSE: The aim of this study is to present the largest normative database using multifocal electroretinography (mfERG) in the context of a multicenter clinical trial. METHODS: This investigational study included 156 eyes from 78 Caucasian subjects aged 45-70 years without known ophthalmic disease or diabetes mellitus; the subjects were recruited from 11 clinical sites in the setting of the EUROCONDOR project. Standardized mfERG acquisition (103 hexagons per eye) was established based on the International Society of Clinical Electrophysiology in Vision. At least one technician per site received both specialized training and certification. The main variables that could have influenced the results were considered in the analyses. RESULTS: The normative database was based on 111 eyes. The overall mean P1-implicit time (IT) was 33.94 ± 1.70 ms, and the mean P1 amplitude was 30.58 ± 5.20 nV/deg2. Age and gender were independently related to predictors of P1-IT but not of P1 amplitude. The responses that were averaged for the 6 rings showed a longer P1-IT time in the fovea, decreasing progressively to the parafovea and perifovea. By contrast, P1 amplitude values sharply decreased with retinal eccentricity. CONCLUSIONS: This normative database can be used as a comparative index of expected normal values in the clinical setting and for examining the effect of studies testing neuroprotective agents.

Histopathological review of 667 cases of oral mucoceles with emphasis on uncommon histopathological variations.

Mucoceles can occur in the oral cavity, appendix, bladder, paranasal sinuses, and lacrimal sac. In the oral cavity, mucoceles arise from pathological alterations in the minor salivary gland ducts. In this study, we aimed to histologically reevaluate cases of oral mucoceles to identify possible variants. A total of 667 slides containing tissue sections stained with hematoxylin and eosin diagnosed as a phenomenon of mucus extravasation were analyzed under light microscopy by 4 previously trained examiners. In 128 cases (19.1%), 1 or more histopathological changes were identified. Twenty cases (2.9%) exhibited collagenous globular structures compatible with myxoglobulosis. In 30 cases (4.49%), dissociation of collagen fibers after mucin extravasation was observed. Fifty-four cases (8.09%) exhibited papillary synovial metaplasia-like change, and 32 (4.79%) showed a significant reduction in the lumen of the cavity due to large papillae. Twenty cases (2.9%) were compatible with superficial mucoceles, and in 11 cases (1.64%), the foamy macrophages showed an unusual solid arrangement, known as clear cell change. It is essential to recognize the possible histopathological changes in oral mucoceles to avoid diagnostic pitfalls.

RETINAL ANGIOMATOUS PROLIFERATION: A Quantitative Analysis of the Fundoscopic Features of the Fellow Eye.

PURPOSE: To quantitatively analyze and compare the fundoscopic features between fellow eyes of retinal angiomatous proliferation and typical exudative age-related macular degeneration and to identify possible predictors of neovascularization. METHODS: Retrospective case-control study. Seventy-nine fellow eyes of unilateral retinal angiomatous proliferation (n = 40) and typical exudative age-related macular degeneration (n = 39) were included. Fundoscopic features of the fellow eyes were assessed using digital color fundus photographs taken at the time of diagnosis of neovascularization in the first affected eye. Grading was performed by two independent graders using RetmarkerAMD, a computer-assisted grading software based on the International Classification and Grading System for age-related macular degeneration. RESULTS: Baseline total number and area (square micrometers) of drusen in the central 1,000, 3,000, and 6,000 µm were considerably inferior in the fellow eyes of retinal angiomatous proliferation, with statistically significant differences (P < 0.05) observed in virtually every location (1,000, 3,000, and 6,000 µm). A soft drusen (≥125 µm) area >510,196 µm2 in the central 6,000 µm was associated with an increased risk of neovascularization (hazard ratio, 4.35; 95% confidence interval [1.56-12.15]; P = 0.005). CONCLUSION: Baseline fundoscopic features of the fellow eye differ significantly between retinal angiomatous proliferation and typical exudative age-related macular degeneration. A large area (>510,196 µm2) of soft drusen in the central 6,000 µm confers a significantly higher risk of neovascularization and should be considered as a phenotypic risk factor.

Treatment of Retinal Vein Occlusion with Ranibizumab in Clinical Practice: Longer-Term Results and Predictive Factors of Functional Outcome.

PURPOSE: To evaluate long-term results and predictors of efficacy in patients with macular edema due to retinal vein occlusion (RVO) treated with intravitreal ranibizumab in a clinical practice setting. METHODS: The clinical records of patients with a minimum follow-up of 3 years were retrospectively analyzed. Sixteen eyes with branch RVO (BRVO) and 16 with central RVO (CRVO) were included. All patients performed cross-sectional evaluation with best-corrected visual acuity (BCVA), spectral domain optical coherence tomography and fluorescein angiography. The foveal avascular zone (FAZ) was assessed and microstructural morphology of the retina was characterized. RESULTS: Follow- up was 42.9 ± 9.0 and 44.8 ± 8.0 months in the CRVO and BRVO groups, respectively. Patients with CRVO received on average 6.9 injections, with a final VA gain of 8.3 ± 15.0 letters (p = 0.05). BRVO eyes had on average 5.9 injections, with a final VA gain of 1.6 ± 21.0 letters (p > 0.05). The FAZ area remained stable in both groups (p > 0.05). Baseline BCVA and disruption of the retinal pigment epithelium (RPE) were predictors of final BCVA (p = 0.001 and 0.011, respectively). CONCLUSION: Although functional outcomes were inferior to those reported in clinical trials, ranibizumab was satisfactory in the long-term treatment of macular edema secondary to RVO and was not associated with increased macular ischemia. Final BCVA depends on baseline BCVA and RPE integrity.

Prevalence of Age-Related Macular Degeneration in Portugal: The Coimbra Eye Study - Report 1.

PURPOSE: To evaluate the age- and gender-specific prevalence of early and late age-related macular degeneration (AMD) in a Portuguese population-based sample. METHODS: All patients aged ≥55 years of a Portuguese primary health-care unit were recruited for a cross-sectional population-based study. Responders underwent complete ophthalmological examination and digital fundus imaging. Early and late AMD was defined according to the International Age-Related Macular Epidemiological Study Group Classification, and the adopted staging for AMD was the same as that used in the Rotterdam study. The age- and gender-adjusted prevalence of early and late forms of AMD was calculated. RESULTS: Of the 4,370 eligible subjects, 3,000 underwent study procedures (68.6% response rate) and 2,975 were included in the analysis; they had a mean age of 68.9 ± 8.6 years. The overall prevalence of early and late AMD was 15.53% (95% CI 14.25-16.88) and 0.67% (95% CI 0.41-1.04), respectively. Neovascular AMD (NV-AMD) and geographic atrophy (GA) accounted for 0.44% (95% CI 0.23-0.75) and 0.27% (95% CI 0.12-0.53) of individuals, respectively. The highest prevalence of advanced AMD was among those aged ≥75 years (1.13% for NV-AMD; 0.63% for GA). CONCLUSIONS: To our knowledge, this is the first AMD epidemiological study in a Portuguese population. The early forms of the disease had a similar prevalence to that of other large-scale population-based cohorts, but late AMD was less frequent than previously reported.

Relationship between the epithelial expression of hMLH1, MDM2, and p63 and lower lip carcinogenesis.

OBJECTIVES: To evaluate the relationship between the epithelial expression of hMLH1, MDM2, and p63 in lower lip carcinogenesis, comparing the immunostaining of these proteins in cases of actinic cheilitis (AC) and lower lip squamous cell carcinoma (SCC). STUDY DESIGN: Forty cases of AC and 40 cases of SCC were studied, both lesions were of lower lip. Histological sections of 3 µm were submitted to immunoperoxidase method, and 1000 cells were counted for immunohistochemical analysis of lesions. The results were analyzed quantitatively, and expression was compared by the Mann-Whitney, Student t-test, or one-way ANOVA, adopting a level of significance of 5%. RESULTS: A higher percentage of epithelial cells expressing hMLH1 was observed in cases of AC without dysplasia or mild dysplasia (721.23 ± 88.116), whereas fewer positive cells were observed in lower lip SSCs (255.03 ± 199.47) when compared to the AC group (P < 0.001). Immunoexpression of MDM2 was higher in SCCs of the lower lip compared with AC (P = 0.019). For p63 protein, the expression was higher in AC than in SCC (P = 0.045). CONCLUSION: The present results showed changes in the immunoexpression of hMLH1, MDM2, and p63 in epithelial cells from premalignant and malignant lip disease, supporting the hypothesis that these alterations are related to the process of lower lip carcinogenesis.

Choroidal thickness in diabetic retinopathy: the influence of antiangiogenic therapy.

PURPOSE: To analyze the effect of anti-vascular endothelial growth factor agents (anti-VEGF) in submacular choroidal thickness (CT) of diabetic retinopathy (DR) patients. METHODS: Cross-sectional study, which included 25 DR patients (50 eyes) divided in 2 groups, according to DR stage and previous treatments: nonproliferative DR and diffuse diabetic macular edema in both eyes, submitted to macular laser in both eyes and anti-VEGF injection only in 1 eye (nonproliferative diabetic retinopathy + diabetic macular edema group, n = 11); and proliferative DR in both eyes, treated with panretinal photocoagulation in both eyes and anti-VEGF injection only in 1 eye (proliferative diabetic retinopathy group, n = 14). In the study visit, all patients underwent optical coherence tomography with enhanced depth imaging protocol. Choroidal segmentation was performed manually. The medium CT in central macular area (CCT) and the CT in centrofoveal B-scan were obtained automatically. RESULTS: The 25 eyes treated with anti-VEGF showed a reduction on CCT (P = 0.002) and subfoveal CT (P = 0.004), compared with the fellow eyes treated with laser only. Independent evaluation of PDR group revealed similar results (CCT, P = 0.02; subfoveal CT, P = 0.03). In nonproliferative diabetic retinopathy + diabetic macular edema group, CCT was also significantly thinner in eyes treated with anti-VEGF (P = 0.04). A correlation between the number of injections and a thinner CT was found in this group (P = 0.03) and in the evaluation of all eyes together (P = 0.03). CONCLUSION: Diabetic eyes treated with anti-VEGF agents have reduced CT.

Genetic variants in ICAM1, PPARGC1A and MTHFR are potentially associated with different phenotypes of diabetic retinopathy.

PURPOSE: To explore phenotype-genotype correlations that may contribute to a better understanding of diabetic retinopathy (DR). PROCEDURES: An exploratory association study was performed to identify genetic variants associated with non-proliferative DR (NPDR) in 307 type 2 diabetic patients who were previously stratified into 3 different phenotypes of NPDR progression. The 307 patients were genotyped for 174 single nucleotide polymorphisms of 11 candidate genes (ACE, AGER, AKR1B1, ICAM1, MTHFR, NOS1, NOS3, PPARGC1A, TGFB1, TNF and VEGFA). RESULTS: Significant associations were observed for PPARGC1A rs16874120 with phenotype A (odds ratio, OR = 0.60, 95% confidence interval, CI 0.36-0.99), ICAM1 rs1801714 with phenotype B (OR = 3.32, 95% CI 1.05-10.50) and both PPARGC1A rs10213440 (OR = 2.00, 95% CI 1.07-3.73) and MTHFR rs1801133 (OR = 1.84, 95% CI 1.08-3.11) with phenotype C. CONCLUSIONS: RESULTS indicate that specific gene variants in ICAM1, PPARGC1A and MTHFR are associated with different NPDR phenotypes, being likely candidates to explain different disease mechanisms underlying the different phenotypes. This is the first study to show correlations between specific gene variants and NPDR phenotypes, opening new perspectives on DR.

Uncovering a New Family Cluster of Gaucher Disease: A Case Report.

Gaucher disease (GD) is a recessive autosomal lysosomal storage disorder caused by a deficiency in glucocerebrosidase, leading to the accumulation of undigested glycolipids in the lysosomes of monocytes and macrophages. Patients with GD exhibit a spectrum of phenotypic heterogeneity and are broadly classified into three subtypes. Type 1 is the most common and is not associated with neurological damage, while types 2 and 3 are more severe, presenting with acute neuropathic and subacute neuropathic symptoms, respectively. A thorough accurate initial multisystemic assessment is crucial for evaluating the damage to all potentially affected organs and determining the disease burden. This case report highlights the intricacies of GD type 1 by providing a thorough exploration of the clinical presentation and showcasing valuable insights into the unique manifestations of the disease. The key feature was his individual and family medical history, which allowed the identification and treatment of another case within the community.