Weight Gain in Early Infancy Impacts Appetite Regulation in the First Year of Life. A Prospective Study of Infants Living in Cyprus.

BACKGROUND: Eating behavior is associated with weight gain in infancy and childhood. Few studies found a bidirectional association between weight gain and eating behavior development in childhood, but there is little data on the association in early infancy, a period critical for the programming of obesity risk. OBJECTIVE: We investigated the bidirectional association between appetite traits and weight gain during the first year of life. METHODS: Participants were part of a cohort of 432 infants born in Cyprus. Appetite traits were measured using the Baby Eating Behavior Questionnaire or the Child Eating Behavior Questionnaire at age 2 to 4 wk, 6 mo, and 12 mo. Weight and length were collected at birth, 4 wk, 6 mo, and 12 mo. Multivariable linear regression was used to analyze associations between appetite traits at 2 to 4 wk and 6 mo and weight for age z-score change (WFAZC) between 4 wk and 6 mo and 6 and 12 mo. Associations were also analyzed in the opposite direction, between WFAZC from birth to 4 wk, 4 wk to 6 mo, and 6 mo to 12 mo and appetite traits at 4 wk, 6 mo, and 12 mo. RESULTS: Satiety responsiveness (SR) at 2 to 4 wk was associated with lower WFAZC from 4 wk to 6 mo (ß: -0.17; 95% CI: -0.30, -0.04) and SR at age 6 mo was associated with lower WFAZC from 6 to 12 mo (ß: -0.09; 95% CI: -0.17, -0.02). WFAZC from 4 wk to 6 mo was associated with higher enjoyment of food at 12 mo (ß: 0.11; 95% CI: 0.01, 0.20), higher food responsiveness at 12 mo (ß: 0.17; 95% CI: 0.04, 0.30), and lower SR at both 6 mo (ß: -0.11; 95% CI: -0.21, -0.01) and 12 mo (ß: -0.14; 95% CI: -0.24, -0.03). CONCLUSIONS: We found a bidirectional association between weight gain and appetite traits in infancy, suggesting that the effect of postnatal weight gain on obesity development is partly mediated by programming of appetite traits.

Baerveldt Aqueous Shunt with or without Mitomycin C Augmentation: A Retrospective Comparison Study.

OBJECTIVE: To evaluate if intraoperative mitomycin C (MMC) influences the success of Baerveldt aqueous shunts. DESIGN: Retrospective comparative case series. PARTICIPANTS: The study population consisted of 88 patients. Fifty-five received intraoperative MMC and 33 did not (controls). METHODS: The medical records of consecutive patients who underwent standalone Baerveldt aqueous shunts at Birmingham Midland Eye Centre, United Kingdom, were retrospectively reviewed. Patients in the MMC group received 0.2 to 0.4 mg/mL of MMC intraoperatively whereas controls did not. MAIN OUTCOME MEASURES: Primary outcome was survival, which was defined as an intraocular pressure (IOP) > 6 mmHg and ≤ 21 mmHg or ≤ 18 mmHg and > 20% IOP reduction from baseline. Further analysis of patients who required medications (qualified) or no medications (complete) was undertaken. Secondary outcomes were IOP, number of glaucoma medications, complications, intraluminal ripcord removal (IRR), and interventions. RESULTS: Average follow-up was 4.7 ± 1.4 years. At year 5, complete success with the ≤ 21 mmHg threshold was significantly higher in MMC vs controls (39.3% vs 17.8%; log rank P = 0.016). Final complete success with the ≤ 18 mmHg threshold was higher in patients with MMC shunts vs controls (38% vs 15.6%; log rank P = 0.0042). Qualified success was not different between patients with MMC shunts and controls with ≤ 21 mmHg (82% vs 93%; log rank P = 0.29) and ≤ 18 mmHg thresholds (70.3% vs 79.3%; log rank P = 0.44). Uveitic patients were also more likely to achieve complete success at both 21 and 18 mmHg thresholds among the patients receiving MMC compared with controls. Mitomycin C was correlated with lower number of medications between month 3 and year 2 post operatively (P < 0.001) and with a lower rate of IRR at all timepoints (P < 0.001). There were no significant differences in the incidence of prolonged hypotony, although MMC cases had higher transient hypotony at year 1 (P = 0.049). CONCLUSIONS: Mitomycin C provides a significant advantage in Baerveldt aqueous shunt survival when considering medication-free success but not in qualified success. Control patients required more medications to control IOP. This study suggests that intraoperative MMC augmentation of Baerveldt aqueous shunt surgery may be advantageous in achieving IOP control without the need for medication but that it may be associated with more transient hypotony episodes. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Survival of Vaccine-Induced Human Milk SARS-CoV-2 IgG, IgA and SIgA Immunoglobulins across Simulated Human Infant Gastrointestinal Digestion.

Breastfeeding can be a vital way of acquiring passive immunity via the transfer of antibodies from the mother to the breastfeeding infant. Recent evidence points to the fact that human milk contains immunoglobulins (Ig) against the SARS-CoV-2 virus, either after natural infection or vaccination, but whether these antibodies can resist enzymatic degradation during digestion in the infant gastrointestinal (GI) tract or indeed protect the consumers remains inconclusive. Herein, we evaluated the levels of IgG, IgA, and secretory IgA (SIgA) antibodies against the spike protein of SARS-CoV-2 in 43 lactating mothers who received at least two doses of either an mRNA-based vaccine (Pfizer/BioNTech, Moderna; n = 34) or an adenovirus-based vaccine (AstraZeneca; n = 9). We also accessed the potential persistence of SARS-CoV-2 IgA, IgG, and secretory IgA (SIgA) antibodies from vaccinated women in the GI tract of the infants by means of a static in vitro digestion protocol. Our data depict that, although slightly reduced, the IgA antibodies produced after vaccination resist both the gastric and intestinal phases of infant digestion, whereas the IgGs are more prone to degradation in both phases of digestion. Additionally, SIgA antibodies were found to greatly resist the gastric phase of digestion albeit showing some reduction during the intestinal phase. The evaluation of the vaccine induced Ig profile of breastmilk, and the extent to which these antibodies can resist digestion in the infant GI tract provide important information about the potential protective role of this form of passive immunity that could help decision making during the COVID-19 pandemic and beyond.

Gonioscopy-Assisted Transluminal Trabeculotomy Following Failed iStent Surgery.

We describe 4 cases of eyes initially treated with phacoemulsification and iStent trabecular microbypass (Glaukos Corporation). These patients subsequently required further surgery and were successfully treated with the removal of the iStent device followed by gonioscopy-assisted transluminal trabeculotomy (GATT), using the iTrack catheter (Ellex Medical Lasers Ltd). Three of the cases had prior first-generation iStent (G1), and 1 had prior second-generation iStent (G2). This case series demonstrates that in selected cases, a further angle procedure in the form of a GATT can show efficacy and durability in the medium term. Our patients had controlled intraocular pressures (IOPs) at 1-year post-GATT: 2 on IOP-lowering therapy and 2 without any IOP-lowering medications. Three patients had transient hyphema and 2 with high IOP in the immediate postoperative period. No patients experienced a decrease in best-corrected visual acuity postoperatively. To the best of our knowledge, there is no prior literature describing this surgical strategy. This series demonstrates that GATT could potentially be an effective procedure in the case of a failed initial iStent microtrabecular bypass.

Macular edema associated with non-infectious uveitis: pathophysiology, etiology, prevalence, impact and management challenges.

Macular edema (ME) is the most common sight-threatening complication in uveitis. The diagnostic and therapeutic management of the uveitic macular edema (UME) might be challenging due to the complex diagnostic workup and the difficulties physicians face to find the underlying cause, and due to its usually recurrent nature and the fact that it can be refractory to conventional treatment. Some of the mild cases can be treated with topical steroids, which can be combined with non-steroid anti-inflammatory drugs. However, immunomodulators such as methotrexate, tacrolimus, azathioprine, cyclosporine and mycophenolate mofetil together with anti-tumor necrosis factor-α (anti-TNF alpha) monoclonal antibodies such as adalimumab and infliximab, may be required to control the inflammation and the associated ME in refractory cases, or when an underlying disease is present. This review of the literature will focus mostly on the non-infectious UME.

Blood Biomarkers of Sensitization and Asthma.

Biomarkers are essential to determine different phenotypes of childhood asthma, and for the prediction of response to treatments. In young preschool children with asthma, aeroallergen sensitization, and blood eosinophil count of 300/µL or greater may identify those who can benefit from the daily use of inhaled corticosteroids (ICS). We propose that every preschool child who is considered for ICS treatment should have these two features measured as a minimum before a decision is made on the commencement of long-term preventive treatment. In practice, IgE-mediated sensitization should be considered as a quantifiable variable, i.e., we should use the titer of sIgE antibodies or the size of skin prick test response. A number of other blood biomarkers may prove useful (e.g., allergen-specific IgG/IgE antibody ratios amongst sensitized individuals, component-resolved diagnostics which measures sIgE response to a large number of allergenic molecules, assessment of immune responses to viruses, level of serum CC16, etc.), but it remains unclear whether these can be translated into clinically useful tests. Going forward, a more integrated approach which takes into account multiple domains of asthma, from the pattern of symptoms and blood biomarkers to genetic risk and lung function measures, is needed if we are to move toward a stratified approach to asthma management.

Temporal changes in the prevalence of childhood asthma and allergies in urban and rural areas of Cyprus: results from two cross sectional studies.

BACKGROUND: The prevalence of childhood asthma and allergies in Cyprus was significantly higher in urban compared to rural areas back in the year 2000, against a background of an overall low prevalence (e.g. current wheeze 6.9%) by comparison to northern European countries. In this study we aimed to assess temporal changes in the prevalence of asthma and allergies in Cyprus after an 8-year interval and to examine whether any differential changes have occurred in urban and rural parts of the island. METHODS: During the academic years 1999-2000 and 2007-2008, the parents of 7-8 year old children residing in the same set of urban and rural areas completed the ISAAC core questionnaire. In addition to providing prevalence estimates of allergic diseases in 2000 and 2008, changes between the two periods were expressed as odds ratios estimated in multiple logistic regression models adjusting for survey participants' characteristics. RESULTS: The prevalence of current wheeze was higher in 2008 (8.7%, 95% confidence interval 7.5%-9.9%, n = 2216) than the previously recorded figure in 2000 (6.9%, 95% CI 6.2%-7.6%, OR = 1.25, 95% CI: 1.02-1.53, n = 4944). Significant increases were also seen in the prevalence of lifetime asthma (11.3% vs. 17.4%, OR = 1.59, CI: 1.36-1.86), eczema (6.8% vs. 13.5%, OR = 1.91, CI: 1.59-2.29) and allergic rhinoconjuctivitis (2.6% vs. 5.2%, OR = 1.82, CI: 1.39-2.41). The prevalence of current wheeze nearly doubled between 2000 and 2008 in rural areas (5.4% vs. 9.7%, OR 1.81, CI: 1.24-2.64) while no significant change was observed in urban areas (7.5% vs. 8.4%, OR 1.08, CI: 0.84-1.37); p value for effect modification = 0.04. Rises in asthma and rhinitis prevalence, but not eczema were also more pronounced in rural compared to urban areas. CONCLUSIONS: The prevalence of allergic diseases in Cyprus is still on the rise; recent increases appear more pronounced among children living in rural areas possibly indicating recent environmental and lifestyle changes in these communities.

Domestic allergen and endotoxin exposure and allergic sensitization in Cyprus.

We investigated the relationship between domestic allergen and endotoxin exposure and allergic sensitization among children in Cyprus. We skin prick tested 128 children aged 15-16 yr (random samples of 85 children with self-reported asthma and 43 healthy controls) and measured their domestic exposure to endotoxin and allergens (mite, cat, and dog). We analyzed the data using multivariate logistic regression (adjusting for gender, area of residence and parental history) and presented the outcomes as odds ratios (OR) and 95% confidence intervals (CI). Among this selected population, 19% of children were sensitized to mite, 15% to cat and 7% to dog. Male gender (OR 2.74, 95% CI 1.18-6.38, p = 0.02), maternal history of allergic disease (OR 3.53, 95% CI 1.13-11.00, p = 0.03), increasing endotoxin (OR 1.58, 95% CI 1.00-2.49, p = 0.05) and residence in the district of Nicosia (OR 2.48, 95% CI 1.01-6.08, p = 0.05) were independent associates of allergic sensitization. Factors associated with mite sensitization were increasing Der p 1 and endotoxin exposure (OR 1.28, 95% CI 1.01-1.62, p = 0.04 and OR 1.76, 95% CI 1.01-3.08, p = 0.05, respectively) and living in an urban area (OR 6.80, 95% CI 1.37-33.67, p = 0.02). Sensitization to domestic pets was associated only with paternal allergic disease (cat: OR 5.68, 95% CI 1.57-23.56, p = 0.02; dog: OR 13.5, 95% CI 1.79-101.73, p = 0.01), but not with pet ownership or specific allergen or endotoxin exposure. In conclusion, mite allergen exposure was associated with sensitization to mite, but there was no association between cat and dog allergen exposure and specific sensitizations. Surprisingly, in this area, increasing endotoxin exposure was associated with an increased risk of sensitization.

Early life environmental control: effect on symptoms, sensitization, and lung function at age 3 years.

We investigated whether environmental control during pregnancy and early life affects sensitization and lung function at the age of 3 years. High-risk children (n = 251) were prenatally randomized to stringent environmental control (active) or no intervention (control). Questionnaires, skin testing, IgE, and specific airway resistance (sRaw) measurement were completed at the age of 3 years. Children in the active group were significantly more frequently sensitized compared with control subjects (at least one allergen by skin tests: risk ratio, 1.61; 95% confidence interval [CI], 1.02-2.55; p = 0.04; mite by IgE: risk ratio, 2.85; 95% CI, 1.02-7.97; p = 0.05). However, sRaw was significantly better in the active group (kiloPascal/second, geometric mean [95% CI]: 1.05 [1.01-1.10] vs. 1.19 [1.13-1.25], p < 0.0001, active vs. control). Maximal flow at functional residual capacity was measured using rapid thoracic compression at the age of 4 weeks in a subgroup. Prospective lung function data (at infancy and 3 years) were obtained in 32 children (14 active and 18 control). There was no difference in infant lung function between the groups, but at 3 years, sRaw was significantly lower in the active compared with control children (p = 0.003). Stringent environmental control was associated with increased risk of mite sensitization but better results for some measurements of lung function in high-risk children at the age of 3 years.