Ophthalmological impairment in patients with congenital cytomegalovirus infection.

Background: Congenital cytomegalovirus (cCMV) infection is a frequent cause of neurosensory impairment. Ocular abnormalities and visual impairment have been reported in a high percentage of symptomatic infants, whereas they are considered uncommon in asymptomatic ones. The paucity of data has made difficult to reach clear recommendations on the ophthalmological follow-up that should be provided. Methods: 250 patients with cCMV infection (123 symptomatic) were enrolled and underwent a series of age-appropriate ophthalmologic, audiologic, and neurodevelopmental examinations from 2002 to 2022. Results: Funduscopic abnormalities were identified at onset in 16/123 (13%) symptomatic infants and in none of the asymptomatic ones (p < 0.001). Chorioretinitis lesions were the most common findings (10/16 cases), while the others showed retinal scars. Lesions were bilateral in 4 patients. No later onset retinal lesions were detected, nor in symptomatic or in asymptomatic children. Five of the 16 (31.5%) symptomatic and none of the asymptomatic subjects showed visual impairment al the last evaluation (p < 0.001). All patients with unfavorable outcome had also neurological impairment. Among symptomatic patients, ocular lesions were associated with central nervous system (CNS) pathological findings in prenatal ultrasonography (p 0.05) and with clinical signs of CNS involvement at birth (p 0.046). No correlation was found with the type of maternal infection and pathological neuroimaging. Conclusions: Chorioretinal lesions are a fairly common finding at birth in neonates with symptomatic cCMV, often associated with long term visual impairment. Asymptomatic infants do not show ophthalmological abnormalities in the short or long term. This information is relevant both to parental counseling and to cost-effective patient management.

Specific antibody titer decay in neonates prenatally exposed to Toxoplasma gondii and their mothers.

BACKGROUND: For infants exposed in utero to Toxoplasma gondii, current guidelines recommend monitoring the specific antibody titer until 12 months of age. In this study, we investigated the antibody titer decay in the mother-infant dyad. METHODS: This is a single center, population-based cohort study of neonates referred for prenatal exposure to Toxoplasma gondii from January 2014 to December 2020. All infants underwent clinical, laboratory, and instrumental investigation for at least 12 months. RESULTS: A total of 670 eligible neonates were referred to the Perinatal Infection Unit of the University Federico II of Naples. 636 (95%) completed the serological follow up until 12 months. Specific IgG antibodies negativization occurred in 628 (98.7%) within 5 months. At 9 and 12 months, all patients had negative IgG. An initial neonatal IgG antibody titer ≥ 200 IU/ml was associated with a longer time to negativization (184 [177.5;256] days when above threshold vs. 139.5 [101;179] days when below it; p < 0.001). Maternal IgG antibody titer ≥ 200 IU/ml at childbirth was also associated to delayed time to negativization in the infant (179 [163;184] days above the threshold vs 125 [96.8;178] days below it; p < 0.001). Specific antibody negativization was irreversible in all patients. CONCLUSIONS: Lower anti-Toxoplasma antibody titers detected at birth in the mother-infant-dyad lead to an earlier and irreversible negativization. This information allows for customisation of the infant follow up program and avoids invasive and expensive tests.

Phenotype and Natural History of Children With Coexistent Inflammatory Bowel Disease and Celiac Disease.

BACKGROUND: Adult patients with both inflammatory bowel disease (IBD) and celiac disease (CeD) have peculiar phenotypic features. This study aimed at describing the characteristics and natural history of children with both IBD and CeD. METHODS: This was a case-control study based on a national registry. Cases included children diagnosed with both IBD and CeD. Two matched IBD controls without CeD, and 2 matched CeD controls were selected for each case. Inflammatory bowel disease phenotype and natural history, comprising growth and pubertal development, were compared between groups. RESULTS: Forty-nine (1.75%) patients with IBD and CeD were identified out of 2800 patients with IBD. Compared with patients with IBD alone, patients with IBD and CeD presented more frequently with autoimmune diseases (odds ratio, 2.81; 95% CI, 0.97-8.37; P = 0.04). Ileocolonic localization (46.1% vs 73.1%), treatment with azathioprine (46.2% vs 71.2%), and anti-TNF biologics (46.2% vs 69.2%) were less common in patients with Crohn's disease and CeD than in patients with Crohn's disease alone. Patients with ulcerative colitis and CeD had an increased risk of colectomy despite similar medical treatments compared with patients with ulcerative colitis alone (13.0% vs 0%). Pubertal delay was more common in patients with IBD and CeD compared with patients with IBD alone (14.9% vs 3.2%; odds artio, 5.24; 95% CI, 1.13-33.0; P = 0.02) and CeD alone (14.9% vs 1.1%; P = 0.002). CONCLUSIONS: Children with IBD and CeD may have peculiar features with a higher risk for autoimmune diseases, colectomy, and pubertal delay compared with IBD alone.

Detrimental effects of melanocortin-1 receptor (MC1R) variants on the clinical outcomes of BRAF V600 metastatic melanoma patients treated with BRAF inhibitors.

Melanocortin-1 receptor (MC1R) plays a key role in skin pigmentation, and its variants are linked with a higher melanoma risk. The influence of MC1R variants on the outcomes of patients with metastatic melanoma (MM) treated with BRAF inhibitors (BRAFi) is unknown. We studied the MC1R status in a cohort of 53 consecutive BRAF-mutated patients with MM treated with BRAFi. We also evaluated the effect of vemurafenib in four V600 BRAF melanoma cell lines with/without MC1R variants. We found a significant correlation between the presence of MC1R variants and worse outcomes in terms of both overall response rate (ORR; 59% versus 95%, P = 0.011 univariate, P = 0.028 multivariate analysis) and progression-free survival (PFS) shorter than 6 months (72% versus 33%, P = 0.012 univariate, P = 0.027 multivariate analysis). No difference in overall survival (OS) was reported, probably due to subsequent treatments. Data in vitro showed a significant different phosphorylation of Erk1/2 and p38 MAPK during treatment, associated with a greater increase in vemurafenib IC50 in MC1R variant cell lines.