Sensitivity and Specificity of the Newborn Infant Parasympathetic Evaluation Index in Pain Assessment of Very Low Birth Weight Infants.

OBJECTIVE: This article describes the results of a study investigating the sensitivity and specificity of the Newborn Infant Parasympathetic Evaluation (NIPE) index for detecting the physiological changes resulting from nociception in painful procedures in very low birth weight (VLBW) infants. STUDY DESIGN: A prospective observational study was carried on of 44 newborns at 23 to 32 weeks' gestational age. The sensitivity and specificity of the NIPE index are analyzed using a receiver operating characteristic curve. Most of the painful procedures performed were skin-lancing and venipunctures. Nonpainful procedures consist of no intervention, with an interval of at least 1 hour with painful procedures in each newborn. RESULTS: The accuracy of the NIPE index to diagnose mild nociceptive stimulation in VLBW newborns is 73.2%. CONCLUSION: The NIPE index is a useful technique for assessing nociceptive stimulation in newborns, presenting less observer-dependent variability than other pain assessment scales. KEY POINTS: · The NIPE index offers an objective assessment of pain.. · Moderate-high sensitivity of the NIPE index in the evaluation of pain in premature newborns.. · Painful procedures in VLBW newborns are reflected as a decrease in the NIPE score..

Early energy restriction in premature infants and bronchopulmonary dysplasia: a cohort study.

Bronchopulmonary dysplasia (BPD) is a multifactor pathology. Animal studies and cohort studies suggest that poor nutrient intake after birth increases the risk of BPD. The objective of the present study was to determine the existence of association between BPD in very low birth weight (VLBW) and energy intake during the first week of life. We recorded in a retrospective cohort study the intake of enteral and parenteral macronutrients during this period by examining the nutritional and clinical history of 450 VLBW newborns admitted to the neonatal intensive care unit. After applying the relevant exclusion criteria, data for 389 VLBW infants were analysed, of whom 159 developed some degree of BPD. Among the newborns with BPD, energy and lipid intake was significantly lower and fluid intake was significantly higher. The energy intake for the 25th percentile in the group without BPD was 1778·2 kJ/kg during the first week of life. An energy intake <1778·2 kJ/kg in this period was associated with a 2-fold increase in the adjusted risk of BPD (OR 2·63, 95 % CI 1·30, 5·34). The early nutrition and the increase of energy intake in the first week of life are associated in our sample with a lower risk of BPD developing.

Sterile Corneal Infiltrates Secondary to Psoriasis Exacerbations: Topical Tacrolimus as an Alternative Treatment Option.

INTRODUCTION: Psoriasis is a common chronic inflammatory skin disease. Ocular manifestations, which occur in 10% to 20% of cases of psoriasis, are usually bilateral and often present during an exacerbation of the psoriasis. Serious corneal involvement is rare but can be devastating. CASE REPORT: Two cases of sterile corneal infiltrates secondary to an exacerbation of psoriasis are presented. Treatment involved the use of 0.02% topical tacrolimus ointment, which resulted in resolution of the symptoms and infiltrates. DISCUSSION AND CONCLUSION: Topical tacrolimus may be considered as an alternative treatment option to corticosteroids in sterile corneal infiltrates.

Mechanical Ventilation, Retinal Avascularity and Rate of Vascularisation: A Triad of Predictors for Retinopathy of Prematurity Treatment.

AIM: The temporal avascular area of the retina and the duration of mechanical ventilation (DMV) may predict the need to treat retinopathy of prematurity (ROP). This study considers whether the rate of retinal vascularisation and related risk factors should be included in a predictive model of the need for ROP treatment. METHODS: This single-centre, observational retrospective case-control study was conducted on 276 preterm infants included in an ROP screening programme. All had undergone at least three examinations of the fundus. The main outcome measures considered were DMV (in days of treatment), the temporal avascular area (in disc diameters, DD) and the rate of temporal retinal vascularisation (DD/week). RESULTS: The multivariate logistic model that best explains ROP treatment (R2 = 63.1%) has three significant risk factors: each additional day of mechanical ventilation (OR, 1.05 [95% CI, 1.02-1.09]; p = 0.001); each additional DD of temporal avascular area (OR, 2.2 [95% CI, 1.7-2.9]; p < 0.001) and a vascularisation rate <0.5 DD/week (OR, 19.0 [95% CI, 6.5-55.5]; p < 0.001). Two tables are presented for calculating the expected need for ROP treatment according to these three risk factors. CONCLUSIONS: A greater DMV, a broad avascular area of the temporal retina at the first binocular screening and slow retinal vascularisation strongly predict the need for ROP treatment. The predictive model we describe must be validated externally in other centres.

Laser fetoscopy ablation for twin-twin transfusion syndrome may reduce the risk of ROP.

PURPOSE: Twin-twin transfusion syndrome (TTTS) is a condition wherein monochorionic twins share a common placenta with placental anastomoses between the two foetal circulations. Most infants who survive TTTS are born prematurely. This study aimed to determine whether fetoscopic laser ablation (FLA) can reduce the risk of retinopathy of prematurity (ROP) and whether TTTS was a risk factor for ROP. METHODS: This single-centre, retrospective, comparative study included 32 monochorionic twins with TTTS matched for gestational age, birthweight and sex to premature twins and singletons without TTTS (n = 68; twins, n = 34; and singletons, n = 34) born between 2003 and 2022. A single ophthalmologist recorded the fundus findings. FLA was performed using Solomon's technique to separate the vascular systems of the twins with TTTS. RESULTS: The gestational age and weight of premature infants with TTTS treated with FLA were significantly higher than those of untreated infants (p = 0.001 and p = 0.001, respectively); however, the hyaline membrane grade was lower (p = 0.004). A significant increase in weight (g/day) (p = 0.002) and lesser avascular area in the peripheral temporal retina (p = 0.045) was observed at postnatal week 4. The risk of ROP in the FLA group was 2.6 times (13.3% vs. 35.3%) lower than that in the non-FLA group; however, this difference was not significant. The incidence of any stage of ROP (25% vs. 18%) and treatment for ROP type 1 (6.25% vs. 5.9%) did not differ significantly between monochorionic twins with TTTS and premature infants without TTTS. CONCLUSION: The gestational age of premature infants with TTTS treated with FLA was higher than that of untreated infants. Moreover, a reduction in complications of prematurity was also observed. Laser fetoscopy in twin-twin transfusion syndrome may reduce the risk of ROP, but the difference was not statistically significant in this small study.

Evaluation of the IL2/IL21, IL2RA and IL2RB genetic variants influence on the endogenous non-anterior uveitis genetic predisposition.

BACKGROUND: Recently, different genetic variants located within the IL2/IL21 genetic region as well as within both IL2RA and IL2RB loci have been associated to multiple autoimmune disorders. We aimed to investigate for the first time the potential influence of the IL2/IL21, IL2RA and IL2RB most associated polymorphisms with autoimmunity on the endogenous non-anterior uveitis genetic predisposition. METHODS: A total of 196 patients with endogenous non-anterior uveitis and 760 healthy controls, all of them from Caucasian population, were included in the current study. The IL2/IL21 (rs2069762, rs6822844 and rs907715), IL2RA (2104286, rs11594656 and rs12722495) and IL2RB (rs743777) genetic variants were genotyped using TaqMan® allelic discrimination assays. RESULTS: A statistically significant difference was found for the rs6822844 (IL2/IL21 region) minor allele frequency in the group of uveitis patients compared with controls (P(-value)=0.02, OR=0.64 CI 95%=0.43-0.94) although the significance was lost after multiple testing correction. Furthermore, no evidence of association with uveitis was detected for the analyzed genetic variants of the IL2RA or IL2RB loci. CONCLUSION: Our results indicate that analyzed IL2/IL21, IL2RA and IL2RB polymorphisms do not seem to play a significant role on the non-anterior uveitis genetic predisposition although further studies are needed in order to clear up the influence of these loci on the non-anterior uveitis susceptibility.

Lack of association between the protein tyrosine phosphatase non-receptor type 22 R263Q and R620W functional genetic variants and endogenous non-anterior uveitis.

OBJECTIVE: Endogenous uveitis is a major cause of visual loss mediated by the immune system. The protein tyrosine phosphatase non-receptor type 22 (PTPN22) gene encodes a lymphoid-specific phosphatase that plays a key role in T-cell receptor (TCR) signaling. Two independent functional missense single nucleotide polymorphisms (SNPs) located within the PTPN22 gene (R263Q and R620W) have been associated with different autoimmune disorders. We aimed to analyze for the first time the influence of these PTPN22 genetic variants on endogenous non-anterior uveitis susceptibility. METHODS: We performed a case-control study of 217 patients with endogenous non-anterior uveitis and 718 healthy controls from a Spanish population. The PTPN22 polymorphisms (rs33996649 and rs2476601) were genotyped using TaqMan allelic discrimination assays. The allele, genotype, carriers, and allelic combination frequencies were compared between cases and controls with χ(2) analysis or Fisher's exact test. RESULTS: Our results showed no influence of the studied SNPs in the global susceptibility analysis (rs33996649: allelic P- value=0.92, odds ratio=0.97, 95% confidence interval=0.54-1.75; rs2476601: allelic P- value=0.86, odds ratio=1.04, 95% confidence interval=0.68-1.59). Similarly, the allelic combination analysis did not provide additional information. CONCLUSIONS: Our results suggest that the studied polymorphisms of the PTPN22 gene do not play an important role in the pathophysiology of endogenous non-anterior uveitis.

Blood products transfusion and retinopathy of prematurity: A cohort study.

AIM: The aim of the study was to assess the influence of blood product transfusions on the development and severity of retinopathy of prematurity (ROP). METHODS: A retrospective cohort study was conducted of very low birth weight (VLBW) newborns with less than 32 weeks gestational age (GA) admitted to the neonatal unit of a tertiary care hospital during the period from 1 January 2008 to 31 December 2021. Data on the degree of ROP and the transfusions received were obtained and analysed. Both univariate and multivariate analyses were performed, by logistic regression. RESULTS: A total of 565 VLBW newborns were recruited, of whom 263 received a red blood cell transfusion prior to 36 weeks corrected GA. The newborns with ROP received significantly more red blood cell transfusions than those not presenting this condition. After adjusting for oxygen therapy and GA, the risk of ROP was found to be 2.77 times higher (95% CI 1.31-5.88) after receiving three or more transfusions, with a 3.95 times higher risk (95% CI 1.40-11.1) of developing severe ROP. Having received the first red blood cell transfusion before 32 weeks corrected GA is associated with an increased risk of ROP (OR 2.18; 95% CI: 1.09-4.36). CONCLUSION: In VLBW neonates, the number of red blood cell transfusions and their administration before 32 weeks corrected GA are important risk factors for ROP.

Speed of Retinal Vascularization in Retinopathy of Prematurity: Risk and Protective Factors.

OBJECTIVE: The objective was to study the risk and protective factors involved in retinal vascular development of preterm infants with retinopathy of prematurity. METHODS: Between 2000 and 2017, 185 preterm infants were included in the protocol for retinopathy of prematurity. Risk factors associated with speed of retinal vascularization <0.5 disc diameter/week were studied in each of them. RESULTS: The statistically significant variables related to retinal vascular development <0.5 DD/w were intubation days, degree 3 of bronchopulmonary dysplasia, weight gain at 4-6 weeks, avascular temporal area, gestational age, number of transfusions, sepsis, number of risk factors, apnea at birth, presence of ductus arteriosus, and days of continuous positive airway pressure therapy. After the multivariate logistic regression analysis, only three variables were found to be significant: intubation days (p=0.005), degree 3 of bronchopulmonary dysplasia (p=0.022), and weight gain at 4-6 weeks (p=0.031). CONCLUSION: In retinopathy of prematurity, degree 3 of bronchopulmonary dysplasia and intubation days cause delayed retinal vascular development, whereas greater postnatal weight gain favors an appropriate rate of retinal vascularization.

Anti-TNF-α therapy in refractory uveitis associated with sarcoidosis: Multicenter study of 17 patients.

OBJECTIVES: To assess anti-TNF-α therapy response in uveitis associated with sarcoidosis refractory to conventional immunosuppressive therapy. METHODS: Open-label, multicenter, retrospective study on patients with sarcoid uveitis who underwent anti-TNF-α therapy because of inadequate response to conventional therapy including corticosteroids and at least 1 systemic synthetic immunosuppressive drug. The main outcome measurements were degree of anterior and posterior chamber inflammation, visual acuity, macular thickness, and immunosuppression load. RESULTS: A total of 17 patients (8 men; 29 affected eyes; mean ± standard deviation age 38.4 ± 16.8; range: 13-76 years) were studied. The patients had bilateral hilar lymphadenopathy (58.8%), lung parenchyma involvement (47.1%), peripheral lymph nodes (41.2%), and involvement of other organs (52.9%). Angiotensin-converting enzyme was elevated in 58.8%. The most frequent ocular pattern was bilateral chronic relapsing panuveitis. The first biologic agent used was adalimumab in 10 (58.8%) and infliximab in 7 (41.2%) cases. Infliximab 5mg/kg intravenously every 4-8 weeks and adalimumab 40mg subcutaneously every 2 weeks were the most common administration patterns. In most cases anti-TNF-α therapy was given in combination with immunosuppressive drugs. The mean duration of follow-up was 33.9 ± 17.1 months. Significant improvement was observed following anti-TNF-α therapy. Baseline results versus results at 2 years from the onset of biologic therapy were the following: the median of cells in the ocular anterior chamber (interquartile range-IQR) 0.5 (0-2) versus 0 (0-0) (p = 0.003), vitritis 0 (0-1.25) versus 0 (0-0) (p = 0.008), macular thickness (391.1 ± 58.8 versus 247 ± 40.5µm) (p = 0.028), and visual acuity 0.60 ± 0.33 versus 0.74 ± 0.27; p = 0.009. The median daily (interquartile range) dose of prednisone was also reduced from 10 (0-30)mg at the onset of the anti-TNF-α therapy to 0 (0-0)mg at 2 years (p = 0.02). Significant reduction was also achieved in the immunosuppressive load. CONCLUSION: Anti-TNF-α therapy is effective in sarcoid uveitis patients refractory to conventional immunosuppressive therapy. Infliximab and adalimumab allowed a substantial reduction in prednisone dose despite having failed standard therapy.

Prenatal and postnatal factors increase risk of severe ROP.

To determine that slower weight premature twins have more risk to develop severe retinopathy of prematurity (ROP) than the higher weight twins. We know that the lower weight twins had less optimal intra-uterine environments than their higher weight twins. We screened 94 consecutive premature twins for ROP. We compared the lower weight twins (n = 47) against their higher weight twins (n = 47). The risk of severe ROP (ROP stage 3 or greater) was significantly higher in the lower weight twin group (p < 0.006). In the same way, in the lower weight twin group the non-perfused area of the temporal retinal artery was higher than that of the other group (an average of 1.2 diameters of the optic nerve head), in the 4-6 postnatal weeks (p < 0.004). The lower weight twin group have an increased risk of severe ROP associated with bacteremia (p = 0.045), or a weight gain less than 7 g per day in the 4-6 postnatal weeks (p = 0.013) or a supplementary postnatal oxygen >4 days (p = 0.007) compared to the higher weight twin group. We confirm Dr. Lee's work that less optimal prenatal factors, in preterm twins, increase the risk of severe ROP.

[Hemodynamic component in glaucoma and its association with risk factors and cardiovascular disease]. / Componente hemodinámico en el glaucoma y su asociación con factores de riesgo y enfermedades cardiovasculares.

BACKGROUND AND OBJECTIVE: We sought to study the association of glaucoma with vascular disease, with 2 independent pathways: the association of glaucoma with cardiovascular disease (CVD) and the study of ocular hemodynamic variables (OHV) in glaucoma. MATERIAL AND METHOD: Cross-sectional study consisting of 73 patients: 25 without glaucoma, 28 primary open-angle glaucoma (POAG) and 20 normal-tension glaucoma (NTG). OHV, cardiovascular risk factors (CVRF) and CVD were determined. RESULTS: We found a greater number of CVRF and CVD in patients affected by POAG (P=.002 and P=.016) and NTG (P=.001 and P=.010) compared to the control group. With regard to OHV, in patients suffering from POAG, we found lower systolic and diastolic velocities and higher resistance index in the central retinal artery (P<.05). Moreover, in both types of glaucoma, we found higher resistance index in the posterior ciliary artery (P<.05). CONCLUSIONS: There is a statistically significant association between the presence of CVD and/or CVRF and glaucomatous disease, a finding that is supplemented with data from the OHV. These values indicate a worst ocular perfusion in patients with glaucomatous disease.

Application of interferon alpha 2b in conjunctival intraepithelial neoplasia: predictors and prognostic factors.

PURPOSE: To test the safety, tolerability, and efficacy of interferon alpha 2b for conjunctival intraepithelial neoplasia (CIN) and to evaluate the risk factors associated with its clinical outcome. A secondary goal is to identify predictors of duration of treatment to achieve good results. METHODS: A prospective, noncomparative case series. Twenty-two patients with CIN were treated with interferon alpha 2b (1 million IU/mL) 4 times daily. Patients were evaluated by slit-lamp biomicroscopy, corneal histopathology, and impression cytology and the same physician carried out the diagnosis in all cases. Patients were monitored for relapses for 48 months after interferon therapy had ended. The following statistical tests were carried out: descriptive, bivariate correlation, and survival curves. RESULTS: Topical therapy eliminated clinical signs of disease in 91% of the cases (20 of 22). The average time to CIN resolution was 3.5 months (range 1-9), with only 4 patients presenting adverse effects (1 irritative conjunctivitis and 3 punctate keratitis). None of the 4 cases experiencing adverse reactions required discontinuation of therapy. Patients living in areas with high ultraviolet radiation levels had a longer clinical resolution (4.2 months) than those living in areas with low UV levels (1.8 months, P=0.01). There was association with statistical significance between the size of the lesion at the third month and treatment duration (P=0.048). CONCLUSION: Topical interferon alpha 2b is an effective and safe treatment option for CIN. The place of residence can be a risk factor; areas like coast with higher UV levels result in a slower clinical resolution than inland areas. The size of the lesion after the third month of treatment with interferon can be a predictor of time to clinical resolution of CIN.

"Oxygen with love" and diode laser treatment decreases comorbidity and avoidable blindness due to retinopathy of prematurity: results achieved in the past 12 years.

AIM: To determine whether the "Oxygen with Love" (OWL) and diode laser treatment provided in a neonatal intensive care unit has reduced the risk of avoidable blindness caused by retinopathy of prematurity (ROP) over the past decade. MATERIALS AND METHODS: A prospective observational cohort study was performed, in which 351 infants were examined for ROP. The inclusion conditions were as follows: preterm infants, birthweight <1500 g or <32 weeks' gestational age, and birth between 1 Jan 2000 to 31 August 2012. From mid-2009, the OWL program was implemented and the ventilation protocols for such infants were amended. We tested whether the incidence of unfavorable structural outcomes of ROP had decreased following these changes. RESULTS: From 2004 to 2012, the survival rates of younger children increased (p < 0.003). From 2005 to 2012, laser treatment rather than cryotherapy was applied, and the incidence of unfavorable structural outcomes of ROP fell from 13% to 5.6% (not significant). From 2009 to 2012, the incidence of ROP decreased from 55% to 29% (p < 0.002). From 1 August 2009 to 31 August 2012, there was less need for ablative treatment for premature infants, with the rate falling from 11.81% to 3.9% (p < 0.03). This improvement was significantly associated with a reduction in the number of days of intubation (p < 0.0017), lower rates of sepsis (p < 0.003), and improvements in postnatal weight gain (p < 0.0002). CONCLUSION: The introduction of the OWL program, together with lower rates of sepsis, improvements in postnatal weight gain, and the use of diode laser treatment, has reduced the incidence of unfavorable structural outcomes of ROP.

Two functional variants of IRF5 influence the development of macular edema in patients with non-anterior uveitis.

OBJECTIVE: Interferon (IFN) signaling plays a crucial role in autoimmunity. Genetic variation in interferon regulatory factor 5 (IRF5), a major regulator of the type I interferon induction, has been associated with risk of developing several autoimmune diseases. In the current study we aimed to evaluate whether three sets of correlated IRF5 genetic variants, independently associated with SLE and with different functional roles, are involved in uveitis susceptibility and its clinical subphenotypes. METHODS: Three IRF5 polymorphisms, rs2004640, rs2070197 and rs10954213, representative of each group, were genotyped using TaqMan® allelic discrimination assays in a total of 263 non-anterior uveitis patients and 724 healthy controls of Spanish origin. RESULTS: A clear association between two of the three analyzed genetic variants, rs2004640 and rs10954213, and the absence of macular edema was observed in the case/control analysis (P FDR =5.07E-03, OR=1.48, CI 95%=1.14-1.92 and P FDR =3.37E-03, OR=1.54, CI 95%=1.19-2.01, respectively). Consistently, the subphenotype analysis accordingly with the presence/absence of this clinical condition also reached statistical significance (rs2004640: P=0.037, OR=0.69, CI 95%=0.48-0.98; rs10954213: P=0.030, OR=0.67, CI 95%=0.47-0.96), thus suggesting that both IRF5 genetic variants are specifically associated with the lack of macular edema in uveitis patients. CONCLUSION: Our results clearly showed for the first time that two functional genetic variants of IRF5 may play a role in the development of macular edema in non-anterior uveitis patients. Identifying genetic markers for macular edema could lead to the possibility of developing novel treatments or preventive therapies.

No evidence of association between common autoimmunity STAT4 and IL23R risk polymorphisms and non-anterior uveitis.

OBJECTIVE: STAT4 and IL23R loci represent common susceptibility genetic factors in autoimmunity. We decided to investigate for the first time the possible role of different STAT4/IL23R autoimmune disease-associated polymorphisms on the susceptibility to develop non-anterior uveitis and its main clinical phenotypes. METHODS: Four functional polymorphisms (rs3821236, rs7574865, rs7574070, and rs897200) located within STAT4 gene as well as three independent polymorphisms (rs7517847, rs11209026, and rs1495965) located within IL23R were genotyped using TaqMan® allelic discrimination in a total of 206 patients with non-anterior uveitis and 1553 healthy controls from Spain. RESULTS: No statistically significant differences were found when allele and genotype distributions were compared between non-anterior uveitis patients and controls for any STAT4 (rs3821236: P=0.39, OR=1.12, CI 95%=0.87-1.43; rs7574865: P=0.59 OR=1.07, CI 95%=0.84-1.37; rs7574070: P=0.26, OR=0.89, CI 95%=0.72-1.10; rs897200: P=0.22, OR=0.88, CI 95%=0.71-1.08;) or IL23R polymorphisms (rs7517847: P=0.49, OR=1.08, CI 95%=0.87-1.33; rs11209026: P=0.26, OR=0.78, CI 95%=0.51-1.21; rs1495965: P=0.51, OR=0.93, CI 95%=0.76-1.15). CONCLUSION: Our results do not support a relevant role, similar to that described for other autoimmune diseases, of IL23R and STAT4 polymorphisms in the non-anterior uveitis genetic predisposition. Further studies are needed to discard a possible weak effect of the studied variant.