The Role of Heparin in Postural Orthostatic Tachycardia Syndrome and Other Post-Acute Sequelae of COVID-19.

The therapeutic management and short-term consequences of the coronavirus disease 2019 (COVID-19) are well known. However, COVID-19 post-acute sequelae are less known and represent a public health problem worldwide. Patients with COVID-19 who present post-acute sequelae may display immune dysregulation, a procoagulant state, and persistent microvascular endotheliopathy that could trigger microvascular thrombosis. These elements have also been implicated in the physiopathology of postural orthostatic tachycardia syndrome, a frequent sequela in post-COVID-19 patients. These mechanisms, directly associated with post-acute sequelae, might determine the thrombotic consequences of COVID-19 and the need for early anticoagulation therapy. In this context, heparin has several potential benefits, including immunomodulatory, anticoagulant, antiviral, pro-endothelial, and vascular effects, that could be helpful in the treatment of COVID-19 post-acute sequelae. In this article, we review the evidence surrounding the post-acute sequelae of COVID-19 and the potential benefits of the use of heparin, with a special focus on the treatment of postural orthostatic tachycardia syndrome.

Epidemiology, clinical features, and classification of 3,404 patients with uveitis: Colombian Uveitis Multicenter Study (COL-UVEA).

PURPOSE: To describe the epidemiology, clinical features, and classification of uveitis in a large cohort of Colombian patients. METHODS: Data were collected from seven ophthalmological referral centers in the four main cities in Colombia. The study included patients with a confirmed diagnosis of uveitis from January 2010 to December 2022. Information on demographics, ophthalmic examination findings, uveitis classification, and etiology was recorded. RESULTS: The study reviewed 3,404 clinical records of patients with uveitis. The mean age at diagnosis was 41.1 (SD 19.0) years, and 54.2% of the patients were female. Overall, 1,341(39.4%) were infectious, 626 (18.4%) non-infectious, and four masquerade syndromes (0.1%). The most common types of uveitis were unilateral (66.7%), acute (48.3%), and non-granulomatous (83%). Anterior uveitis was the most common anatomical localization (49.5%), followed by posterior uveitis (22.9%), panuveitis (22.3%), and intermediate uveitis (5.2%). A diagnosis was established in 3,252 (95.5%) cases; idiopathic was the most common cause (27.7%), followed by toxoplasmosis (25.3%) and virus-associated uveitis (6.4%). The age group between 30 and 50 exhibited the highest frequency of uveitis. CONCLUSION: This multicenter study comprehensively describes uveitis characteristics in Colombian patients, providing valuable insights into its demographic and clinical features. The study findings emphasize the need to continue updating the changing patterns of uveitis to improve diagnosis and treatment strategies for diseases associated with intraocular inflammation.

Index and Repeat Ablation for Atrial Fibrillation in Older versus Younger Patients: A Propensity-Score Matching Analysis.

Catheter ablation is a well-established rhythm control therapy in atrial fibrillation (AF). Although the prevalence of AF increases dramatically with age, the prognosis and safety profile of index and repeat ablation procedures remain unclear in the older population. The primary endpoint of this study was to assess the arrhythmia recurrence, reablation and complication rates in older patients. Secondary endpoints were the identification of independent predictors of arrhythmia recurrence and reablation, including information on pulmonary vein (PV) reconnection and other atrial foci. Older (n=129, ≥70 years) and younger (n=129, <70 years) patients were compared using a propensity-score matching analysis based on age, gender, obesity, hypertension, dyslipidemia, diabetes mellitus, dilated left atrium, severe obstructive sleep apnea, cardiac disease, left systolic ventricular function, AF pattern and ablation technique. Arrhythmia recurrence and reablation were evaluated in both groups using a Cox regression analysis in order to identify predictors. During a 30-month follow-up period, there were no significant differences between older and younger patients in the arrhythmia-free survival (65.1% and 59.7%; log-rank test p=0.403) and complication (10.1% and 10.9%; p>0.999) rates after the index ablation. However, the reablation rate was significantly different (46.7% and 69.2%; p<0.05, respectively). In those patients who underwent reablation procedure (redo subgroups), there were no differences in the incidence of PV reconnection (38.1% redo-older and 27.8% redo-younger patients; p=0.556). However, the redo-older patients had lower reconnected PVs per patient (p<0.01) and lower atrial foci (2.3 and 3.7; p<0.01) than the redo-younger patients. A further important finding was that age was not an independent predictor of arrhythmia recurrence or reablation. Our data reveal that the AF index ablation in older patients had a similar efficacy and safety profile to younger patients. Therefore, age alone must not be considered a prognostic factor for AF ablation but the presence of limiting factors such as frailty and multiple comorbidities.

A Multisite Electronic Health Record Integrated Remote Monitoring Intervention for Hypertension Improvement: Protocol for a Randomized Pragmatic Comparative Effectiveness Trial.

BACKGROUND: Hypertension is a major contributor to various adverse health outcomes. Although previous studies have shown the benefits of home blood pressure (BP) monitoring over office-based measurements, there is limited evidence comparing the effectiveness of whether a BP monitor integrated into the electronic health record is superior to a nonintegrated BP monitor. OBJECTIVE: In this paper, we describe the protocol for a pragmatic multisite implementation of a quality improvement initiative directly comparing integrated to nonintegrated BP monitors for hypertension improvement. METHODS: We will conduct a randomized, comparative effectiveness trial at 3 large academic health centers across California. The 3 sites will enroll a total of 660 participants (approximately n=220 per site), with 330 in the integrated BP monitor arm and 330 in the nonintegrated BP control arm. The primary outcome of this study will be the absolute difference in systolic BP in mm Hg from enrollment to 6 months. Secondary outcome measures include binary measures of hypertension (controlled vs uncontrolled), hypertension-related health complications, hospitalizations, and death. The list of possible participants will be generated from a central data warehouse. Randomization will occur after enrollment in the study. Participants will use their assigned BP monitor and join site-specific hypertension interventions. Cross-site learning will occur at regular all-site meetings facilitated by the University of California, Los Angeles Value-Based Care Research Consortium. A pre- and poststudy questionnaire will be conducted to further evaluate participants' perspectives regarding their BP monitor. Linear mixed effects models will be used to compare the primary outcome measure between study arms. Mixed effects logistic regression models will be used to compare secondary outcome measures between study arms. RESULTS: The study will start enrolling participants in the second quarter of 2023 and will be completed by the first half of 2024. Results will be published by the end of 2024. CONCLUSIONS: This pragmatic trial will contribute to the growing field of chronic care management using remote monitoring by answering whether a hypertension intervention coupled with an electronic health record integrated home BP monitor improves patients' hypertension better than a hypertension intervention with a nonintegrated BP monitor. The outcomes of this study may help health system decision makers determine whether to invest in integrated BP monitors for vulnerable patient populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT05390502; clinicaltrials.gov/study/NCT05390502. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/45915.

Postural orthostatic tachycardia syndrome and other related dysautonomic disorders after SARS-CoV-2 infection and after COVID-19 messenger RNA vaccination.

The COVID-19 pandemic has caused a challenge for our society due to the post-acute sequelae of the disease. Persistent symptoms and long-term multiorgan complications, known as post-acute COVID-19 syndrome, can occur beyond 4 weeks from the onset of the COVID-19 infection. Postural orthostatic tachycardia syndrome (POTS) is considered a variety of dysautonomia, which is characterized by chronic symptoms that occur with standing and a sustained increase in heart rate, without orthostatic hypotension. POTS can lead to debilitating symptoms, significant disability, and impaired quality of life. In this narrative review, the etiopathogenic basis, epidemiology, clinical manifestations, diagnosis, treatment, prognosis, and socioeconomic impact of POTS, as well as other related dysautonomic disorders, after COVID-19 infection and SARS-CoV-2 postvaccination, were discussed. After a search conducted in March 2023, a total of 89 relevant articles were selected from the PubMed, Google Scholar, and Web of Science databases. The review highlights the importance of recognizing and managing POTS after COVID-19 infection and vaccination, and the approach to autonomic disorders should be known by all specialists in different medical areas. The diagnosis of POTS requires a comprehensive clinical assessment, including a detailed medical history, physical examination, orthostatic vital signs, and autonomic function tests. The treatment of POTS after COVID-19 infection or vaccination is mainly focused on lifestyle modifications, such as increased fluid and salt intake, exercise, and graduated compression stockings. Pharmacotherapy, such as beta-blockers, fludrocortisone, midodrine, and ivabradine, may also be used in selected cases. Further research is needed to understand the underlying mechanisms, risk factors, and optimal treatment strategies for this complication.

Effectiveness of Goal-Directed and Outcome-Based Financial Incentives for Weight Loss in Primary Care Patients With Obesity Living in Socioeconomically Disadvantaged Neighborhoods: A Randomized Clinical Trial.

Importance: Financial incentives for weight management may increase use of evidence-based strategies while addressing obesity-related economic disparities in low-income populations. Objective: To examine the effects of 2 financial incentive strategies developed using behavioral economic theory when added to provision of weight management resources. Design, Setting, and Participants: Three-group, randomized clinical trial conducted from November 2017 to May 2021 at 3 hospital-based clinics in New York City, New York, and Los Angeles, California. A total of 1280 adults with obesity living in low-income neighborhoods were invited to participate, and 668 were enrolled. Interventions: Participants were randomly assigned to goal-directed incentives, outcome-based incentives, or a resources-only group. The resources-only group participants were given a 1-year commercial weight-loss program membership, self-monitoring tools (digital scale, food journal, and physical activity monitor), health education, and monthly one-on-one check-in visits. The goal-directed group included resources and linked financial incentives to evidence-based weight-loss behaviors. The outcome-based arm included resources and linked financial incentives to percentage of weight loss. Participants in the incentive groups could earn up to $750. Main Outcomes and Measures: Proportion of patients achieving 5% or greater weight loss at 6 months. Results: The mean (SD) age of the 668 participants enrolled was 47.7 (12.4) years; 541 (81.0%) were women, 485 (72.6%) were Hispanic, and 99 (14.8%) were Black. The mean (SD) weight at enrollment was 98.96 (20.54) kg, and the mean body mass index (calculated as weight in kilograms divided by height in meters squared) was 37.95 (6.55). At 6 months, the adjusted proportion of patients who lost at least 5% of baseline weight was 22.1% in the resources-only group, 39.0% in the goal-directed group, and 49.1% in the outcome-based incentive group (difference, 10.08 percentage points [95% CI, 1.31-18.85] for outcome based vs goal directed; difference, 27.03 percentage points [95% CI, 18.20-35.86] and 16.95 percentage points [95% CI, 8.18-25.72] for outcome based or goal directed vs resources only, respectively). However, mean percentage of weight loss was similar in the incentive arms. Mean earned incentives was $440.44 in the goal-directed group and $303.56 in the outcome-based group, but incentives did not improve financial well-being. Conclusions and Relevance: In this randomized clinical trial, outcome-based and goal-directed financial incentives were similarly effective, and both strategies were more effective than providing resources only for clinically significant weight loss in low-income populations with obesity. Future studies should evaluate cost-effectiveness and long-term outcomes. Trial Registration: ClinicalTrials.gov Identifier: NCT03157713.

Clinical patterns and risk factors in scleritis: a multicentric study in Colombia.

PURPOSE: This study aims to describe the clinical characteristics of scleritis in a large cohort of Colombian patients and identify factors associated with the clinical presentation. METHODS: Retrospective case series of patients with scleritis from 2015 to 2020. Clinical records were obtained from seven uveitis referral centers in Colombia. Patients with a diagnosis of episcleritis were excluded. RESULTS: We evaluated 389 patients with scleritis (509 eyes). There was a female predominance (75.6%) with a mean age of 51 ± 15 years. Most cases were noninfectious (94.8%) and unilateral (69.2%). The most frequent type of inflammation was diffuse anterior scleritis (41.7%), followed by nodular scleritis (31.9%) and necrotizing scleritis (12.3%). Systemic autoimmune diseases were found in 41.3% of patients, the most common being rheumatoid arthritis (18.5%) and granulomatosis with polyangiitis (5.9%). Polyautoimmunity was found in 10.4% of those with a systemic autoimmune disease. The most frequent treatment was systemic steroids (50.9%), followed by systemic NSAIDs (32.4%). Steroid-sparing immunosuppression was required in 49.1% of patients. Systemic autoimmune diseases were more common in patients with necrotizing scleritis and those older than 40 years of age. Best-corrected visual acuity of 20/80 or worse at presentation was more common in necrotizing scleritis and subjects with associated uveitis, ocular hypertension, or who were over 40 years of age. CONCLUSIONS: This is the first study in Colombia and the largest in Latin America describing the clinical characteristics and presentation patterns of scleritis. The most common presentation was in females, with unilateral, anterior diffuse noninfectious scleritis. Systemic autoimmune diseases and polyautoimmunity were frequent, as was the need for steroid-sparing immunosuppression. Age over 40 and necrotizing scleritis were associated with higher odds of having a systemic autoimmune disease and worse visual acuity at presentation.

An open source toolkit for repurposing Illumina sequencing systems as versatile fluidics and imaging platforms.

Fluorescence microscopy is a key method in the life sciences. State of the art -omics methods combine fluorescence microscopy with complex protocols to visualize tens to thousands of features in each of millions of pixels across samples. These -omics methods require precise control of temperature, reagent application, and image acquisition parameters during iterative chemistry and imaging cycles conducted over the course of days or weeks. Automated execution of such methods enables robust and reproducible data generation. However, few commercial solutions exist for temperature controlled, fluidics coupled fluorescence imaging, and implementation of bespoke instrumentation requires specialized engineering expertise. Here we present PySeq2500, an open source Python code base and flow cell design that converts the Illumina HiSeq 2500 instrument, comprising an epifluorescence microscope with integrated fluidics, into an open platform for programmable applications without need for specialized engineering or software development expertise. Customizable PySeq2500 protocols enable experimental designs involving simultaneous 4-channel image acquisition, temperature control, reagent exchange, stable positioning, and sample integrity over extended experiments. To demonstrate accessible automation of complex, multi-day workflows, we use the PySeq2500 system for unattended execution of iterative indirect immunofluorescence imaging (4i). Our automated 4i method uses off-the-shelf antibodies over multiple cycles of staining, imaging, and antibody elution to build highly multiplexed maps of cell types and pathological features in mouse and postmortem human spinal cord sections. Given the widespread availability of HiSeq 2500 platforms and the simplicity of the modifications required to repurpose these systems, PySeq2500 enables non-specialists to develop and implement state of the art fluidics coupled imaging methods in a widely available benchtop system.

Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models.

Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.

Spatiotemporal dynamics of molecular pathology in amyotrophic lateral sclerosis.

Paralysis occurring in amyotrophic lateral sclerosis (ALS) results from denervation of skeletal muscle as a consequence of motor neuron degeneration. Interactions between motor neurons and glia contribute to motor neuron loss, but the spatiotemporal ordering of molecular events that drive these processes in intact spinal tissue remains poorly understood. Here, we use spatial transcriptomics to obtain gene expression measurements of mouse spinal cords over the course of disease, as well as of postmortem tissue from ALS patients, to characterize the underlying molecular mechanisms in ALS. We identify pathway dynamics, distinguish regional differences between microglia and astrocyte populations at early time points, and discern perturbations in several transcriptional pathways shared between murine models of ALS and human postmortem spinal cords.

Astigmatismo y aberraciones corneales en ojos con Iridociclitis Heterocrómica de Fuchs / Corneal astigmatism and aberrations in patients with Fuchs heterochromic iridocyclitis

Introducción: La Iridociclitis Heterocrómica de Fuchs (IHF) es la causa del 2 a 7% de las uveítis anteriores, el astigmatismo corneal como condición de la IHF y como posible causa de la disminución de la visión, ha sido una entidad muy poco estudiada hasta el momento, tiene una gran importancia debido a que por la anisometropía que podría generar, puede llevar a alteraciones de la agudeza visual. Objetivo: Evaluar la existencia de astigmatismo corneal y/o aberraciones corneales inherentes a los ojos con Iridociclitis Heterocrómica de Fuchs. Diseño del estudio: Estudio transversal, analítico, de fuentes primarias. Método: Se realizó muestreo por conveniencia, en el cual se incluyeron 44 ojos de 22 pacientes con diagnóstico de IHF unilateral o bilateral. Para cada caso, se realizó tomografía corneal (Pentacam® AXL - OCULUS) y aberrometria (OPD-Scan III® - NIDEK) y se compararon ojos enfermos con los ojos sanos. Resultados: Se encontró una mediana de 1.35 (RIC: 0.50 ­ 1.70) para el astigmatismo de la cara anterior de los ojos enfermos .vs. 0.8 (RIC: 0.7 ­ 1.1) para el astigmatismo de la cara anterior de los ojos sanos (p= 0.135). Se identificó un astigmatismo en cara anterior >1.00 D en el 61.5% de los ojos enfermos .vs. 27.8% de los ojos sanos (p= 0.027) con un RR de 2.15. No se encontró una diferencia estadísticamente significativa entre los ojos enfermos y los ojos sanos para las aberraciones analizadas. Conclusión: El presente estudio no demuestra la existencia de astigmatismo o aberraciones inherentes a la IHF, pero evidencia una tendencia de mayor astigmatismo en los ojos con IHF, que posiblemente podría lograr significancia estadística con una muestra mayor.

Background: Fuchs heterochromic iridocyclitis (FHI) represents 2 to 7% of cases of anterior uveitis. To date, few studies have addressed corneal astigmatism as an inherent condition and as possible cause of decreased visual acuity in FHI patients. This may be relevant since the generated anisometropia may lead to alterations in visual acuity. Objective: To evaluate the presence of corneal astigmatism and/or corneal aberrations in patients with FHI. Study design: Analytic cross sectional study. Method: A convenient sampling was performed. The sample included 44 eyes of 22 patients with unilateral or bilateral FHI. All participants were studied by corneal tomography (Pentacam® AXL ­ OCULUS) and aberrometry (OPDScan III® - NIDEK); measurements of diseased and healthy eyes were compared. Results: Twenty-two patients were enrolled in this study. The mean age at diagnosis was 46.9 +/- 12 years, and 40.9% were men. FHI eyes exhibited a median astigmatism of the anterior surface of 1.35D (IQR: 0.50 ­ 1.70), compared to 0.8D (IQR: 0.7 ­ 1.1) observed in healthy eyes (p= 0.135). Anterior surface astigmatism >1.00 diopters (D) was found in 61.5% of diseased eyes compared to 27.8% of healthy eyes, with a risk ratio of 2.15. Regarding corneal aberrations, no statistically significant differences were identified between diseased and healthy eyes for the analyzed aberrations. Conclusion: While our current data does not show statistically signifi cant differences between groups that support that corneal astigmatism or aberrations are inherent to FHI-aff ected eyes, our study does show a trend that suggests increased presence of clinically relevant astigmatism in eyes with FHI. Statistical significance may be achieved with a larger sample size.

Bilateral Iris Depigmentation and Ocular Hypotony as End-Stage Manifestations of Untreated Vogt-Koyanagi-Harada Disease.

PURPOSE: To describe severe bilateral iris depigmentation and persistent ocular hypotony as end-stage manifestations of untreated Vogt-Koyanagi-Harada disease. METHODS: We present the clinical findings and diagnostic studies performed for three patients with bilateral iris depigmentation. RESULTS: Vogt-Koyanagi-Harada disease in late recurrent stage was diagnosed in three patients with bilateral severe iris depigmentation and persistent ocular hypotony. CONCLUSIONS: Early diagnosis and treatment of inflammation are crucial factors in the clinical outcome of Vogt-Koyanagi-Harada disease. When left undiagnosed and untreated from early stages, severe iris depigmentation and ocular hypotony, uncommon manifestations of this disease, can develop.

Desenlaces en pacientes operados con queratoprótesis boston tipo 1 en un centro oftalmológico especializado en la ciudad de Medellín / Outcomes in patients with boston type 1 keratoprosthesis in a specialized center in Medellín

Objetivo: reportar las características y descenlaces de pacientes con queratoprótesis Boston tipo 1. Diseño: estudio observacional descriptivo de corte transversal. Método: se incluyeron los pacientes operados con queratoprótesis Boston tipo 1 residentes en Colombia, mayores de 17 años, sin queratoprótesis previas y que tuviera más de 6 meses de seguimiento, para un total de 39 ojos de 39 pacientes. La cirugía se indicó en los casos con o sin queratoplastia previa que tuvieran agudeza visual (AV) igual o inferior a cuenta dedos y déficit de limbo bilateral o vascularización corneal profunda en más de 3 cuadrantes. Se recolectó y analizó la información de la historia clínica en forma retrospectiva y prospectiva. Las variables principales fueron: agudeza visual, retención del dispositivo y complicaciones. Se realizó un análisis univariado presentando los resultados en frecuencias absolutas y porcentajes para las variables categóricas y para las variables cuantitativas como promedio y desviación estándar (DE) si tienen distribución normal o como mediana y rango intercuartil si no tienen distribución normal. Resultados: La mediana de seguimiento fue de 53.5 meses (rango 6 meses a 10 años). La mayoría de pacientes (66.7%) habían tenido previamente queratoplastia penetrante. El diagnóstico de base fue en 53.8% condiciones no inflamatorias yen 46.2% condiciones inflamatorias. La AV preoperatoria en todos los ojos estaba entre percepción de luz y cuenta dedos; posterior a la cirugía el 97.4% tuvieron mejoría de la AV. Para el fi nal del seguimiento la AV permaneció mejor que la preoperatoria en 53.8%, fue igual a esta en 17.94% y peor que esta en 28.2%. Hubo necrosis periprostética en 28.2%, y 38.5% tuvieron recambio del dispositivo. Al final del seguimiento 89.7% de los pacientes tenían una queratoprótesis in-situ. Conclusión: la queratoprótesis Boston tipo 1 es una opción viable para mejorar la AV en pacientes con trasplantes de córnea fallidos o en quienes se prevé alta tasa de fallo o rechazo de este. En la gran mayoría de los pacientes se logra mejoría inicial significativa de la AV, la cual se mantiene al final del seguimiento en más de la mitad de ellos. Refinamientos progresivos en la técnica quirúrgica y el manejo postoperatorio disminuirán las complicaciones que llevan a la perdida visual progresiva

Purpose: to report characteristics and outcomes in patients with Boston type 1 keratoprosthesis. Design: observational descriptive cross-sectional study. Method: Patients with Boston type 1 queratoprosthesis who were living in Colombia, 17 years or older, without previous keratoprosthesis and with more than 6 months follow up were included, for a fi nal of 39 eyes from 39 patients. Surgery was indicated for those with or without previous keratoplasty who had visual acuity (VA) of counting fi ngers or worse and bilateral limbal stem cell deficiency or deep corneal vascularization in more than 3 quadrants. Information was collected retrospectively and prospectively from medical registries and was analyzed. Main variables were: visual acuity, device retention and complications. An univariate analysis was conducted and results are presented in absolute frequencies and percentages for categoric variables and for quantitative variables in average and standard deviation (SD) if they have normal distribution and in median and interquartile range if they do not have normal distribution. Results: Median follow up was 53.5 months (range 6 months to 10 years). Most patients (66.7%) had previous penetrating keratoplasty. Baseline diagnoses were in 53.8% non-infl ammatory conditions and in 46.2% inflammatory conditions. Preoperative VA ranged between light perception and counting fingers in all eyes; aft er surgery 97.4% had improvement in VA. By the end of follow up VA remained better than preoperative in 53.8%, was the same as preoperative in 17.94% and worse than preoperative in 28.2%. There was periprosthetic necrosis in 28.2%, and 38.5% had keratoprothesis exchange. At the end of follow up 89.7% of patients had a keratoprosthesis in-situ. Conclusion: Boston type 1 keratoprosthesis is a viable option to improve VA in patients with previously failed corneal transplants or in cases that anticipate bad prognosis for keratoplasty. In most patients there was a signifi cant initial improvement in vision, and more than half of them retained better than initial VA on their last follow up. Further refinements in surgical technique and postoperative care would decrease complications that lead to progressive visual loss.

Comparison of 4 techniques for limbal-conjunctival autograft fixation in primary pterygium surgery.

PURPOSE: To compare 4 limbal-conjunctival autograft fixation techniques-conventional suture, commercial fibrin glue, autologous fibrin glue, and cautery-in primary nasal pterygium surgery. METHODS: This is a retrospective and descriptive study. The postoperative patient discomfort, graft edema, ocular inflammation, and other complications of 4 limbal-conjunctival autograft fixation techniques in primary nasal pterygium surgery were evaluated. RESULTS: Postoperative patient discomfort was significantly lower with the sutureless techniques (p<0.001), with fixation with cautery having the lowest rate of discomfort. Graft edema and ocular inflammation during the early postoperative period were significantly higher when fibrin glue techniques were used (p<0.001). The recurrence rate did not show a statistically significant difference (p = 0.682) among the 4 groups. CONCLUSION: In primary nasal pterygium surgery, limbal-conjunctival autograft fixation using cautery is the technique with the lowest postoperative discomfort rate and without a statistically significant increase in recurrence rate when compared to conventional suture and fibrin glue techniques.

Contrast-enhanced T2-FLAIR MR imaging in patients with uveitis.

To report MRI findings which reflect a pathological inflammatory condition of the uveal tract. This study includes single-center retrospective case series of five patients with clinical diagnosis of uveitis. There were 1 male (20 %) and 4 female patients (80 %). The average age was 29.6 years (range 25-38 years). Patients and 50 age-range-matched control subjects were scanned using a 1.5 T scanner. Ten additional control subjects scanned at 3 T were evaluated to have reference images at that high field. All patients (n = 5, 100 %) presented uveal tract enhancement on post-contrast T2-FLAIR fat-suppressed images and only 2 (40 %) had enhancement on T1-weighted images. The enhancement was anterior in 2 (40 %), pan-uveal in 2 (40 %), and posterior in 1 patient (20 %). Two patients (40 %) had unilateral increased vitreous signal on T2-FLAIR. One patient (20 %) had bilateral retrobulbar fat enhancement in both post-contrast T2-FLAIR and T1-weighted images. Post-contrast T2-FLAIR images can reveal abnormal enhancement of the uveal tract and retrobulbar fat as well as increased vitreous signal in patients with uveitis. In our small series, the sensitivity of post-contrast T2-FLAIR was higher than the conventional post-contrast T1-weighted images. Nonetheless, when bilateral uveal tract enhancement is present, there should be discretion before calling uveitis because the finding has been reported in different eye conditions as well as in a small percentage of healthy subjects at 1.5 T. In addition, it should be noted that post-contrast T2-FLAIR enhancement of the uveal tract is a normal finding at 3 T imaging.

Spectrum of Clinical Signs and Genetic Characterization of Gelatinous Drop-Like Corneal Dystrophy in a Colombian Family.

PURPOSE: To describe the clinical signs of gelatinous drop-like corneal dystrophy (GDLD) in a consanguineous Colombian family and determine the underlying genetic cause. METHODS: We performed ocular examination of available family members and bidirectionally Sanger sequenced the GDLD-associated gene, TACSTD2. In one individual, the presence of subepithelial amyloid was confirmed with biopsy. RESULTS: The parents were consanguineous and 5 of their 10 children had GDLD. Typical mulberry subepithelial deposits with subepithelial vascularization were present in 3 individuals; 2 individuals only had mild polymorphic anterior stromal opacity. We identified a homozygous TACSTD2 missense mutation, c.551A>G, p.(Tyr184Cys), in the affected family members. Both parents were heterozygous for the mutation, and unaffected siblings were either heterozygous or homozygous wild-type for this allele. In the Colombian population, this mutation has a minor allele frequency of 0.53%. CONCLUSION: The clinical presentation of GDLD in this family was variable and does not solely support an age-dependent progression of the phenotype, suggesting that environmental or other genetic factors can modify phenotypic expression. The relatively high prevalence of this mutation in the Colombian population suggests that other individuals may have undiagnosed subclinical disease.

Treatment with a novel oleic-acid-dihydroxyamphetamine conjugation ameliorates non-alcoholic fatty liver disease in obese Zucker rats.

Fatty liver disease is one of the main hepatic complications associated with obesity. To date, there are no effective treatments for this pathology apart from the use of classical fibrates. In this study, we have characterized the in vivo effects of a novel conjugation of oleic acid with an amphetamine derivative (OLHHA) in an animal model of genetic obesity. Lean and obese Zucker rats received a daily intraperitoneal administration of OLHHA (5 mg kg(-1)) for 15 days. Plasma and liver samples were collected for the biochemical and molecular biological analyses, including both immunohistochemical and histological studies. The expression of key enzymes and proteins that are involved in lipid metabolism and energy homeostasis was evaluated in the liver samples. The potential of OLHHA to produce adverse drug reactions or toxicity was also evaluated through the monitoring of interactions with hERG channel and liver cytochrome. We found that OLHHA is a drug with a safe pharmacological profile. Treatment for 15 days with OLHHA reduced the liver fat content and plasma triglyceride levels, and this was accompanied by a general improvement in the profile of plasma parameters related to liver damage in the obese rats. A decrease in fat accumulation in the liver was confirmed using histological staining. Additionally, OLHHA was observed to exert anti-apoptotic effects. This hepatoprotective activity in obese rats was associated with an increase in the mRNA and protein expression of the cannabinoid type 1 receptor and a decrease in the expression of the lipogenic enzymes FAS and HMGCR primarily. However, changes in the mRNA expression of certain proteins were not associated with changes in the protein expression (i.e. L-FABP and INSIG2). The present results demonstrate that OLHHA is a potential anti-steatotic drug that ameliorates the obesity-associated fatty liver and suggest the potential use of this new drug for the treatment of non-alcoholic fatty liver disease.

Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice.

Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD) in wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. Additionally, HFD-fed IL-6(-/-) mice were also chronically treated with recombinant IL-6 (rIL-6). Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1) and signal transducer and activator of transcription-3 (STAT3), increased AMP kinase phosphorylation (p-AMPK), and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). The HFD-fed IL-6(-/-) mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/ß), FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6 -/-: mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/ß, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis.