Intravitreal Aflibercept vs Laser Therapy for Retinopathy of Prematurity: Two-Year Efficacy and Safety Outcomes in the Nonrandomized Controlled Trial FIREFLEYE next.

Importance: Prospective long-term data after retinopathy of prematurity (ROP) treatment with anti-vascular endothelial growth factor injections vs laser therapy are scarce. The FIREFLEYE (Aflibercept for ROP IVT Injection vs Laser Therapy) next trial is prospectively evaluating the long-term efficacy and safety outcomes following ROP treatment with intravitreal aflibercept vs laser therapy. Objective: To evaluate 2-year ophthalmic and safety outcomes after 0.4-mg aflibercept injection or laser therapy in the 24-week randomized (2:1) FIREFLEYE trial (FIREFLEYE outcomes previously reported). Design, Setting, and Participants: This prospective nonrandomized controlled trial performed in 24 countries in Asia, Europe, and South America (2020-2025) follows up participants treated in the FIREFLEYE randomized clinical trial (2019-2021) through 5 years of age. Participants included children born very or extremely preterm (gestational age ≤32 weeks) or with very or extremely low birth weight (≤1500 g) who were previously treated with a 0.4-mg injection of aflibercept compared with laser therapy for severe acute-phase ROP. Data for the present interim analysis were acquired from March 18, 2020, to July 25, 2022. Interventions: Complications of ROP treated at investigator discretion (no study treatment). Main Outcomes and Measures: Efficacy end points included ROP status, unfavorable structural outcomes, ROP recurrence, treatment for ROP complications, completion of vascularization, and visual function. Safety end points included adverse events and growth and neurodevelopmental outcomes. Results: Overall, 100 children were enrolled (median gestational age, 26 [range, 23-31] weeks; 53 boys and 47 girls). Of these, 21 were Asian, 2 were Black, 75 were White, and 2 were of more than 1 race. At 2 years of age, 61 of 63 children (96.8%) in the aflibercept group vs 30 of 32 (93.8%) in the laser group had no ROP. Through 2 years of age, 62 of 66 (93.9%) in the aflibercept group and 32 of 34 (94.1%) in the laser group had no unfavorable structural outcomes. No new retinal detachment occurred during the study. Four children in the aflibercept group (6.1%) were treated for ROP complications before 1 year of age (2 had preexisting end-stage disease and total retinal detachment; 1 had reactivated plus disease; and 1 had recurrent retinal neovascularization not further specified). Most children were able to fix and follow a 5-cm toy (aflibercept group, 118 of 122 eyes [96.7%] among 63 children; laser group, 62 of 63 eyes [98.4%] among 33 children). High myopia was present in 9 of 115 eyes (7.8%) among 5 children in the aflibercept group and 13 of 60 eyes (21.7%) among 9 children in the laser group. No relevant differences in growth and neurodevelopmental outcomes by Bayley Scales of Infant and Toddler Development, Third Edition and Vineland Adaptive Behavior Scales, Second Edition were identified. Conclusions and Relevance: In this nonrandomized follow-up of a randomized clinical trial comparing treatment of severe acute-phase ROP with 0.4-mg injection of aflibercept and laser, disease control was stable and visual function was appropriate in children through 2 years of age. No adverse effects on safety, including growth and neurodevelopment, were identified. These findings provide clinically relevant long-term information on intravitreal aflibercept injection therapy for ROP. Trial Registration: ClinicalTrials.gov Identifier: NCT04015180.

Sex differences in an old adult sample with substance use disorder: A 6 months follow-up study.

Substance use disorder (SUD) is a worldwide concern that has its own particularities regarding age and sex. This study aims to assess the differences between old SUD women and men regarding socio-demographics, clinical factors and outcomes. A 6-months follow-up longitudinal study was conducted in an outpatient center, on a convenience sample of 115 SUD old adults (≥65 years old, average age of 71.57). Descriptive, bivariate, and multivariate analyses were performed. Data showed statistical significant differences between men and women related to sociodemographic variables (marital status, coexistence, criminal records and stress factors), medical and psychiatric conditions (women suffer higher rates of depression and anxiety, with worse health-related quality of life), family records (women had more presence of family psychiatric records) and SUD related parameters (men tend to use more alcohol, had an early onset, consume higher doses, report more craving and more tobacco life use while women had higher rates of prescription drugs use). At 6-month follow-up, the whole sample showed excellent rates of adherence and abstinence, without sex differences. The study points out sex differences on several sociodemographic and clinical variables, indicating their specific needs. This research could facilitate better approaches by considering a sex perspective in SUD old adults.

Length of illness does not predict cognitive dysfunction in chronic fatigue syndrome.

Neuropsychological studies have shown cognitive impairment in chronic fatigue syndrome (CFS), particularly in information-processing speed. The aim of this study was to examine the evolution of cognitive impairment in CFS. The evolution is one of the most disabling aspects of the CFS, and it has received little attention in the literature. Fifty-six women with CFS were assessed with neuropsychological tests. Patients were divided into three groups based on the duration of the disease. There were no differences between groups in terms of cognitive function. The cognitive impairment in CFS was not found to be more severe with longer disease duration. These data suggest that there is no progressive cognitive impairment in patients with CFS. Therefore, the cognitive deficits in CFS should be treated with cognitive rehabilitation programs focused on improving emotional distress associated to the illness and on promoting functional abilities.

Effects of branched-chain amino acids supplementation in patients with cirrhosis and a previous episode of hepatic encephalopathy: a randomized study.

OBJECTIVES: Protein intake impacts on nutritional status and may determine the recurrence of hepatic encephalopathy (HE). A low-protein diet has been considered the standard treatment after an episode of HE, while branched-chain amino acids (BCAA) have been shown to improve minimal HE. We performed a study to investigate the long-term effects of supplementing a protein-controlled diet with BCAA. METHODS: A randomized, double-blind, multicenter study that included 116 patients with cirrhosis and a previous episode of HE was conducted in four tertiary care hospitals. All patients received a standard diet of 35 kcal/kg per day and 0.7 g of proteins/kg per day and a supplement of 30 g of BCAA (BCAA group) or maltodextrin (MDX group) during 56 weeks. RESULTS: The actuarial risk of remaining free of HE did not differ between groups (BCAA=47%, MDX=34%, P=0.274), but patients in the BCAA group exhibited a better outcome on two neuropsychological tests and an increase in the mid-arm muscle circumference. Recurrence was associated with low plasma albumin at baseline and a decrease in sodium and an increase in creatinine during follow-up. Patients with recurrence of HE exhibited a lack of improvement in global cognitive function. CONCLUSIONS: Diet supplementation with BCAA after an episode of HE does not decrease recurrence of HE. However, supplementation with BCAA improves minimal HE and muscle mass. Identification of risk factors for recurrence of HE may allow the development of new preventive therapies that could decrease the neuropsychological sequelae of repeated episodes of HE.

SPECT imaging for brain improvement quantification in a patient with cerebrotendinous xanthomatosis.

Cerebrotendinous xanthomatosis is a rare recessive autosomal disease caused by mutations of the sterol 27-hydroxylase gene (CYP27), which leads to reduced synthesis of bile acids, particularly chenodeoxycholic acid (Cali et al, J Biol Chem. 1991;266:7779-7783; Gallus et al, Neurol Sci. 2006;27:143-149). The disease is characterized by progressive neurologic dysfunction due to accumulation of cholestanol in neurologic tissues (Moghadasian et al, Arch Neurol. 2002;59:527-529; Selva-O'Callaghan et al, Rheumatology. 2007;46:1212-1213). Long-term treatment with chenodeoxycholic acid can arrest or even reverse progression of the disease (Pierre et al, J Inherit Metab Dis. In press).Brain SPECT with 740 MBq of Tc-99m ethyl cysteinate dimmer, using a double-head gamma camera (Siemens E.cam) with high-resolution, low-energy parallel collimators was performed in our patient at onset and 2 years after starting chenodeoxycholic acid treatment. SPECT acquisitions were performed using a 360-degree orbit, 1 image/30 seg/3 degree, and 128 × 128 matrix. Reconstruction was by means of filtered back-projection, Butterworth 5/0.25, without attenuation correction. Pre- and post-SPECT dicom images were reoriented into Talairach space using NeuroGam (Segami Corporation). To visually identify abnormal perfusion regions, volume render brain image was computed, where abnormal perfusion regions were found by comparing with age-matched normal database, and Brodmann areas (BA) were quantified. Pre- versus post-treatment changes were computed by means of relative percentage between counts. Post-treatment SPECT showed better perfusion than pretreatment SPECT with an increase between 5% and 10% in frontal cortex (BA 9, BA 24, BA 32, BA 46, BA 47), parietal cortex (BA 5, BA 31), and temporal cortex (BA 20, BA 22, BA 28, BA 36, BA 37, BA 38), and with an increase of more than 10% in frontal cortex (BA 45) and parietal cortex (BA 23). This case illustrates the benefit of bile acid therapy for halting and even reversing neurologic retardation in this condition.

[The role of depression in cognitive impairment in patients with chronic fatigue syndrome]. / El rol de la depresión en el déficit cognitivo del paciente con síndrome de fatiga crónica.

BACKGROUND AND OBJECTIVE: To analyze the role of depression in cognitive deficits of patients with chronic fatigue syndrome (CFS). PATIENTS AND METHODS: 57 women with CFS were assessed by neuropsychological tests that included measures of attention: CalCap, Mental control of the WMS-III, PASAT, forward and backward digits (WAIS-III), symbol digit modalities test (SDMT); executive functions: Stroop Test, Trail Making Test (TMT A y B), FAS, Tower of London; memory: Auditory-Verbal Learning Test (AVL), Rey Complex Figure (RCF), and psychomotor skills: Grooved Pegboard. The raw scores on the tests were adjusted according to normative data and transformed to T scores. The sample was divided into two groups based on the presence or absence of depression, assessed by clinical interview and administration of the Hospital Anxiety and Depression Scale (HADS). This study compared neuropsychological test scores between the two groups. RESULTS: CFS patients showed cognitive deficit in attention and executive functions, regardless of the presence of depression. There were no significant differences between the two CFS groups. CONCLUSIONS: The cognitive impairments in patients with CFS are not secondary to the presence of depression. These results should be taken into account in the implementation of therapeutic programs in these patients.

A long-term study of changes in the volume of brain ventricles and white matter lesions after successful liver transplantation.

BACKGROUND: A prolonged survival in liver transplant recipients due to a better management exposes them to multiple factors that can impair neurologic function in the long term. METHODS: Twenty-two patients were studied by brain magnetic resonance and completed a neuropsychologic assessment shortly before liver transplant, 6 to 12 months after (short term), and 6 to 9 years (long term) after liver transplant. Thirteen healthy controls matched by age were studied in parallel. RESULTS: An enlargement in the ventricular size (an indirect measure of brain volume) was observed in the short term (+8%) and in the long term after liver transplant (+22%); the size of ventricles was larger than in healthy controls. In addition, a progression in the volume of focal T2 white matter lesions (an index of small vessel cerebrovascular disease) was detected in the long term (+49%) and was related to vascular risk factors in those with larger increases (>12.5% per year). Neuropsychologic function showed a significant improvement after liver transplant and remained stable in the long term, except for memory loss in those patients with larger increases in white matter lesions. CONCLUSIONS: Improvement in neuropsychologic function after successful liver transplant can be demonstrated up to 9 years. However, these patients experience a progressive accumulation of focal T2 brain lesions and show a smaller brain volume than controls, which can be related to their previous cirrhosis. A good management to minimize brain injury before transplantation and an accurate treatment of vascular risk factors may be important to prevent consequences on cognitive function.