A multi-institutional feasibility study of intra-arterial chemotherapy in children with retinoblastoma. A Children's Oncology Group study (COG ARET12P1).

BACKGROUND: Intra-arterial chemotherapy (IA) as a treatment to salvage the eye with advanced retinoblastoma is increasingly utilized based on successes reported by institutions around the world mainly through retrospective studies. OBJECTIVE: To study the feasibility of delivering melphalan directly into the ophthalmic artery in a multi-institutional prospective study in children with newly diagnosed unilateral group D retinoblastoma. METHODS: The Children's Oncology Group (COG) initiated study ARET12P1 in 2014 and was open to nine institutions. Eligible patients older than six months of age were enrolled. The feasibility of delivering three injections of melphalan into the ophthalmic artery every 28 days was assessed. RESULTS: Nine institutions participated in this trial. Fourteen patients were enrolled, two of whom were unevaluable for feasibility. Four patients experienced a feasibility failure. In two patients, the ophthalmic artery could not be accessed for the second IA injection, in one the artery could not be accessed for the first injection, and one patient experienced grade 4 hypotension during the procedure. CONCLUSION: Delivery of prescribed therapy within the context of this study did not meet the feasibility goals of the study with only a 67% feasibility success rate. These results should caution centers that plan to initiate this treatment and suggest investment in training to achieve technical expertise or referral to centers with expertise.

Unilateral acute iris transillumination syndrome with glaucoma and iris pigment epithelium dispersion simulating iris melanoma.

Purpose: To report a patient with a unilateral presentation of glaucoma, pain, and acute iris transillumination syndrome simulating iris melanoma. Observations: A 53-year-old male presented with blurred vision and pain in his right eye several weeks following a respiratory sinus infection managed by oral azithromycin. Examination of the right eye was notable for elevated intraocular pressure of 46 mm Hg, an irregular mid-dilated pupil, and diffuse iris transillumination with pigmentary seeding on the iris surface, in the anterior chamber angle, and on the sclera, suspicious for diffuse iris melanoma with glaucoma and extrascleral extension. Ultrasound biomicroscopy (UBM) of the right eye revealed circumferential anterior chamber angle and trabecular meshwork involvement by an infiltrative process corresponding to the pigmented cells noted clinically, while the ciliary body was unremarkable. Following enucleation, histopathology showed extensive necrosis of the iris pigment epithelium, sphincter, and dilator muscles with melanophagic infiltration in the anterior chamber angle and episclera, mild chronic non-granulomatous iridocyclitis, and no evidence of a melanocytic neoplasm. Although immunohistochemical studies for herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus, and cytomegalovirus were negative, qualitative real-time polymerase chain reaction on paraffin-embedded tissue detected HSV-1 DNA. The combined clinical, pathologic, and molecular findings were compatible with unilateral acute iris transillumination syndrome, likely HSV-1 associated. Conclusion and Importance: Unilateral acute iris transillumination syndrome with diffuse iris pigment epithelial loss can simulate iris melanoma. Prompt herpes viral studies may be informative.

Características clínicas y demográficas de los niños hospitalizados con infección por SARS-CoV-2

Introducción: en marzo de 2020 se registraron los primeros casos de infección por SARS-CoV-2 en Uruguay y se decretó la emergencia sanitaria. Objetivo: describir las características clínicas demográficas de los menores de 15 años hospitalizados con infección por SARS-CoV-2 en el período 13 de marzo de 2020 al 30 de septiembre de 2021 en el Hospital Pediátrico del Centro Hospitalario Pereira Rossell, centro de referencia público de Uruguay. Metodología: estudio descriptivo, retrospectivo, en el que se describen edad, manifestaciones clínicas, comorbilidades, severidad, tratamiento y evolución. Resultados: se hospitalizaron 207 niños con una frecuencia de 1,6%. La mediana (rango intercuartil) de edad fue 1,5 años (3 meses - 8 años); <1 año 44%; 54% de sexo masculino. Presentaron comorbilidades, 59 niños. Fueron sintomáticos, 71%. De los sintomáticos, presentaron síntomas leves 48%. Las manifestaciones clínicas fueron respiratorias en 96 (65%) y no respiratorias en 51 (fiebre sin foco 15, digestivas 19, exantema viral 3, SIM-Ped S 10 y atípicas 3). Treinta niños ingresaron a unidad de cuidados intensivos (UCI) y tres requirieron ventilación invasiva. Estos pacientes presentaron comorbilidades, tuvieron más días de fiebre y necesitaron oxigenoterapia que los que no requirieron UCI. Un paciente de 2 años con comorbilidades falleció. Conclusión: la frecuencia de hospitalizaciones fue de 1,6%. La mayoría de los niños sintomáticos presentaron formas leves. En los sintomáticos las manifestaciones fueron respiratorias. Los hallazgos en esta serie aportan al conocimiento del comportamiento de la infección por SARS-CoV-2 en niños.

Introduction: in March 2020, the first cases of SARS CoV-2 infection were registered in Uruguay and a health emergency was decreed. Objective: To describe the clinical and demographic characteristics of children under 15 years of age hospitalized with SARS-CoV-2 infection from March 13, 2020, to September 30, 2021, at Pereira Rossell Pediatric Hospital, a public reference center in Uruguay. Method: descriptive, retrospective study describing age, clinical manifestations, comorbidities, severity and treatment. Results: a total of 207 children were hospitalized, with a frequency of 1.6%. The median (interquartile range) age was 1.5 years (3 months - 8 years); <1 year accounted for 44%, and 54% were male. Comorbidities were present in 59 children. 71% of them were symptomatic, and among the symptomatic cases, 48% presented mild symptoms. Clinical manifestations were respiratory in 96 (65%) cases and non-respiratory in 51 (fever without a focus 15, gastrointestinal 19, viral exanthem 3, pediatric inflammatory multisystem syndrome 10, and atypical 3). Thirty patients were admitted to the Intensive Care Unit (ICU), and 3 required invasive ventilation. These patients had comorbidities, more days of fever, and required oxygen therapy compared to those who did not need ICU. One 2-year-old patient with comorbidities died. Conclusion: the hospitalization frequency was 1.6%. Most symptomatic children had mild forms of the disease. Among the symptomatic cases, respiratory manifestations were predominant. The findings from this series contribute to the understanding of the behavior of SARS-CoV-2 infection in children.

Introdução: Os primeiros casos de infecção por SARS CoV-2 no Uruguai foram registrados em março de 2020 quando foi decretada a emergência sanitária. Objetivo: descrever as características clínicas e demográficas das crianças menores de 15 anos internadas com infecção por SARS CoV-2 no período 13 de março de 2020 - 30 de setembro de 2021 no Hospital Pediátrico do Centro Hospitalar Pereira Rossell, centro público de referência no Uruguai. Metodologia: estudo descritivo, retrospectivo, incluindo idade, manifestações clínicas, comorbidades, gravidade, tratamento e evolução. Resultados: 207 crianças foram internadas com infecção por SARS CoV-2 correspondendo a frequência de 1,6% do total de crianças hospitalizadas no período estudado. A mediana (intervalo interquartil) de idade foi de 1,5 anos (3 meses - 8 anos) dos quais 44% eram <1 ano 44% e 54% do sexo masculino. 59 crianças apresentaram comorbidades. 71% eram sintomáticas sendo que 48% delas apresentaram sintomas leves. As manifestações clínicas foram respiratórias em 96 (65%) e não respiratórias em 51 (febre sem foco 15, digestiva 19, exantema viral 3, SIM-Ped S 10 e atípico 3). 30 crianças foram internadas na Unidade de Terapia Intensiva e 3 precisaram de ventilação invasiva; esses pacientes apresentavam comorbidades, necessitaram de oxigenoterapia e tiveram mais dias de febre do que aqueles que não necessitaram de UTI. Uma paciente de 2 anos com comorbidades faleceu. Conclusão: a frequência de internações foi de 1,6%. A maioria das crianças sintomáticas apresentou formas leves. Nas sintomáticas as manifestações foram respiratórias. Os achados desta série contribuem para o conhecimento do comportamento da infecção por SARS CoV-2 em crianças.

PRIMARY CENTRAL NERVOUS SYSTEM AND VITREORETINAL LYMPHOMA MIMICKING VIRAL RETINITIS IN A YOUNG PATIENT.

BACKGROUND/PURPOSE: The purpose of this study was to report a young immunocompetent patient with primary central nervous system and vitreoretinal lymphoma initially presenting with peripheral retinitis. METHODS: This study is a case report. RESULTS: A 31-year-old woman presented with 20/60 vision in her left eye, vitreous haze, and peripheral retinal whitening. Intravitreal and oral antivirals were initiated for presumed acute retinal necrosis. Anterior chamber paracentesis was negative for viral nucleotide. Subretinal infiltrates developed, and vitreous biopsy was performed and interpreted as "negative except for rare yeast." Antifungal therapy was initiated. She developed multiple unilateral cranial neuropathies with multifocal areas of enhancement on neuroimaging. Lumbar puncture cytology was negative for neoplastic cells. After further worsening, aforementioned specimens were sent to a specialized ophthalmic pathology laboratory and the diagnosis revised to lymphoma of the diffuse B-cell type. Initial disease regression was seen after combined systemic and intraocular chemotherapy; unfortunately, the patient suffered a central nervous system recurrence and died from systemic complications 1 year later. CONCLUSION: There has been an increased incidence of primary central nervous system and vitreoretinal lymphoma in young patients. Although vitreous biopsy is the diagnostic gold standard for vitreoretinal lymphoma, a risk of false negative interpretation exists. A high index of suspicion and expert interpretation of pathology may be necessary to secure the correct diagnosis.

Multiplying Brown Spots.

PURPOSE: Bilateral diffuse uveal melanocytic proliferation (BDUMP) is a paraneoplastic syndrome affecting the eye that is a sign of poor prognosis of underlying malignancy.This is the first documented case to show serial and sustained improvement of BDUMP following immunotherapy in the setting of primary non-small cell carcinoma of the lung. OBSERVATIONS: A 65-year-old man reported a gradual decrease in vision and floaters in the right eye after cataract surgery. Fundus examination demonstrated diffuse multiple brown subretinal lesions bilaterally. Next generation sequencing of melanocytic tissue of the patient described in this case revealed a specific RB1 c.411A>T (p.Glu137Asp) variant with an allele frequency of 44.8%, consistent with heterozygosity. Plasma samples from the patient and a control patient with no history of cancer and/or paraneoplastic syndrome were cultured with neonatal melanocytes, which revealed a greater than 180% increase in proliferation of normal neonatal melanocytes compared to the control. Pembrolizumab therapy was initiated which resulted in shrinkage and stabilization of the lesions documented in serial diagnostic testing. CONCLUSIONS: In conclusion, we report a cytologically and serologically confirmed case of BDUMP in a patient with a primary non-small cell carcinoma of the lung. Next generation sequencing of melanocytic tissue of the patient described in this case revealed a specific RB1c.411A>T (p.Glu137Asp) variant with an allele frequency of 44.8%, consistent with heterozygosity. Furthermore, we show documented serial improvement in the patient's ocular and systemic disease with treatment. This case as one of the longest surviving confirmed cases of a patient with BDUMP.

Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma.

Retinoblastoma is a cancer of the infant retina primarily driven by loss of the Rb tumor suppressor gene, which is undruggable. Here, we report an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell-surface receptor for SFRP2 in retinoblastoma cells; that CXADR functions as a "dependence receptor," transmitting a growth-inhibitory signal in the absence of SFRP2; and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induces nitric oxide and profoundly inhibits retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation and is amenable to therapeutic intervention.

Malignant teratoid intraocular ciliary body medulloepithelioma in a 5-year-old male with corresponding somatic copy number alteration profile of aqueous humor cell-free DNA.

BACKGROUND: Intraocular, ciliary body, medulloepithelioma (CBME) is a rare tumor of the nonpigmented ciliary body epithelium, typically presenting in childhood. We describe a case of CBME. MATERIALS AND METHODS: Ocular examination and imaging guided diagnostic and treatment decisions. Aqueous humor (AH) liquid biopsy was collected from the affected eye at eventual enucleation. Whole genome sequencing (WGS) was employed to determine somatic copy number alterations (SCNA) in AH cell-free DNA (cfDNA). Tumor sample was analyzed using various assays to evaluate for oncogenic mutations and SCNAs. Histopathology determined diagnosis. RESULTS: A 5-year-old male with glaucoma and cataract in the left eye (OS) experienced worsening left eye pain and redness. There was no light perception OS and the eye was hypotonus. Anterior segment exam showed complete cataract and rubeosis iridis. Ocular B-scan ultrasound OS revealed an intraocular lesion with calcifications and retinal detachment. Orbital MRI suggested left globe hypercellularity. An infiltrative lesion involving the ciliary body was seen in the left eye on examination under anesthesia. Left eye enucleation was performed in the setting of pain, blindness, and tumor, with anterior chamber paracentesis for AH liquid biopsy collection. SCNA profile of AH cfDNA demonstrated loss of copy of chromosomes 4, 6, and 9. Tumor was negative for clinically significant mutations or SCNAs. Histopathology diagnosed malignant teratoid CBME. CONCLUSIONS: We present a case of CBME and include the unique SCNA profile of AH cfDNA from the enucleated eye. This case suggests utility of AH liquid biopsy in distinguishing between differential diagnoses for intraocular mass lesions.

[Epidemiological and clinical characteristics of children with COVID-19 cared for in a private health provider in Uruguay]. / Características epidemiológicas y clínicas de los niños con COVID-19 asistidos en un prestador de salud privado de Uruguay.

BACKGROUND: After the detection of the first cases of SARS-CoV-2 and the declaration of a health emergency in the country, community transmission of the virus remained low to moderate until November 2020, later becoming medium and high. Children under 15 years of age constitute the least affected group. The diagnosis is confirmed by RT-qPCR. The usefulness of the CT (cycle threshold) is discussed. AIM: To describe the epidemiological and clinical characteristics of children infected with SARS-CoV-2 and the relationship between the CT value and clinical presentation. METHOD: A descriptive, retrospective study was carried out in patients under 16 years of age with SARS-CoV-2 infection, assisted by a health provider in Montevideo between epidemiological week (EW) 3 of2020 and EW 9 of2021. Clinical variables, epidemiological notion, severity and evolution were described. The CT value at diagnosis was recorded and compared with the presence of symptoms. RESULTS: Patients under 16 years of age represented 16.6% of the total infected (794 in 4,792). 70% of the cases occurred between the months of January and February 2021. 67.6% presented intradomiciliary contact. The mean age was 7.5 ± 4.1 years, 51% were male. 55% presented symptoms and 45% were asymptomatic; no significant differences were observed in the mean, mode and age range of both groups. None presented comorbidities. In the group of 440 symptomatic patients, 55% presented fever: 32% associated with other symptoms, mainly upper respiratory symptoms, and 23% as the only symptom. The CT value was obtained in 536 of the 794 patients (67.5%). The mean CT was 29.7+5.8 in the symptomatic group vs. 31.5 ± 5.7 in asymptomatic patients (p > 0.05). Three patients were hospitalized, none required intensive care and none died. CONCLUSIONS: The prevalence and incidence of SARS-CoV-2 infection in children accompany that of adults and the majority had mild or asymptomatic forms, without complications. In this series, the CT value was not different in symptomatic and asymptomatic children. Close household contact was the main source of infection.

Three-year outcomes of uveal melanoma treated with intra-operative ultrasound-guided iodine-125 brachytherapy using custom-built eye plaques.

Purpose: The aim of this study was to demonstrate that uveal melanoma (UM) treated with eye plaque brachytherapy (EPB) with intra-operative ultrasound (IOUS) guidance results in increased local control. Material and methods: A retrospective study was conducted among 212 patients with 214 UM tumors treated by iodine-125 EPB with IOUS guidance from 2013 to 2019. 85 Gy was prescribed to tumor apical height or 5 mm from inner sclera, whichever was greater. Lesions were treated to 95% of 85 Gy at 2 mm margin from tumor edge. Local failure (LF), distant metastasis (DM), and radiation-related toxicity were recorded. Results: Median tumor apical height was 3.3 mm. COMS stage was 90 small (42.1%), 81 medium (37.9%), and 43 large (20.1%). Most patients had gene expression profile (GEP) class available, with 119 (55.6%), 30 (14.0%), 55 (25.7%) cases classified as 1A, 1B, and 2, respectively. Median dose at apex for tumor height > 5 mm and ≤ 5 mm was 85.0 Gy and 120.6 Gy, respectively. Outcomes data for 180 patients with over 12 months follow-up were reported. Mean follow-up was 37.3 months. Rates of LF and DM were 0.0% and 12.2%, respectively. Actuarial estimates of 5-year DM for class 1A, 1B, and 2 tumors were 2.5%, 0.0%, and 57.8%, respectively. 87 patients (48.3%) developed radiation-related toxicities. Conclusions: The excellent local control rate amongst lesions ranging across all sizes and GEP classes emphasizes the importance of image-guided brachytherapy with IOUS. We report favorable 5-year DM rates compared to established rates. Acceptable rate and severity of radiation-related toxicities were observed.

Contemporary trends in management of uveal melanoma.

Purpose: In the management of uveal melanoma, eye plaque brachytherapy (EPBT) has replaced enucleation as the standard of care for small size tumors that require treatment, and for medium size tumors. In the modern era, EPBT is being utilized more frequently for certain large tumors as well. While there is prospective randomized evidence to support utilization of EPBT for tumors of appropriate dimensions, it is unclear what the actual practice patterns are across the United States. The purpose of this publication was to look at contemporary trends in the management of uveal melanoma across the United States to determine whether practices are appropriately adopting EPBT, and to investigate demographic and socio-economic factors that might be associated with deviations from this standard of care. Material and methods: The National Cancer Database was queried (2004-2015) for patients with uveal melanoma. Data regarding tumor characteristics and treatment were collected. Two-sided Pearson χ2 test was used to compare categorical frequencies between patients who received globe preserving treatments vs. those who received enucleation. Multivariable logistic regression modeling was used to determine characteristics predictive for receiving enucleation. Results: The enucleation rate for small/medium tumors (≤ 10 mm apical height and ≤ 16 mm basal diameter) decreased from 20% in 2004 to 10% in 2015. The EPBT rate for large tumors increased from 30% in 2004 to 45% in 2015. Numerous demographic and socio-economic factors were found to be associated with higher rates of enucleation. Conclusions: The overall trend across the nation is a decreased enucleation rate for small/medium tumors, and an increased EPBT rate for large tumors. A fraction of patients who should be candidates for EPBT are instead receiving enucleation, and in this study, we have shown that certain adverse demographic factors are associated with this.

AUTOSOMAL DOMINANT MÜLLER CELL SHEEN DYSTROPHY: Clinical, Histopathologic, and Genetic Assessment in an Extended Family With Long Follow-Up.

BACKGROUND: Autosomal dominant Müller cell dystrophy is a rare condition we described in 1991. It is characterized by a striking sheen appearance on the retinal surface with progressive retinal changes leading to disorganization and atrophy with a decreased b-wave electroretinograms. MATERIALS AND METHODS: We examined 45 members of a 4-generation family. Fifteen subjects from three generations were found with the disease, without gender predilection. Seven patients underwent ophthalmic examination including fundus examination, intravenous fluorescein angiogram, spectral-domain optical coherence tomography, and electroretinogram. Six patients have a 30-year follow-up. Histopathology examination was performed on eyes of the eldest patient. Whole exome sequencing was done in four affected subjects. RESULTS: Findings include a decreased visual acuity, abnormal cellophane-like sheen of the vitreoretinal interface, a "plush" nerve fiber layer, and characteristic macular changes. Electroretinogram showed a selective b-wave diminution. Intravenous fluorescein angiogram presented perifoveal hyperfluorescence and capillary leakage. Spectral-domain optical coherence tomography revealed cavitations involving inner and later outer retinal layers with later disorganization. Histopathologic findings included Müller cell abnormalities with cystic disruption of inner retinal layers, pseudoexfoliation in anterior segment, and amyloidosis of extraocular vessels. Pedigree analysis suggests an autosomal dominant inheritance with late onset. DNA analysis demonstrated a previously undescribed heterozygous missense p.Glu109Val mutation in transthyretin. CONCLUSION: To the best of our knowledge, this is the first family reported with this disorder. Our data support the hypothesis that autosomal dominant Müller cell dystrophy is a distinct retinal dystrophy affecting Müller cells. Mutations in transthyretin gene may manifest as a predominantly retinal disorder.

Características epidemiológicas y clínicas de los niños con COVID-19 asistidos en un prestador de salud privado de Uruguay / Epidemiological and clinical characteristics of children with COVID-19 cared for in a private health provider in Uruguay

INTRODUCCIÓN: Tras la detección de los primeros casos de SARS-CoV-2 y declararse la emergencia sanitaria en el país, la transmisión comunitaria del virus se mantuvo baja a moderada hasta noviembre de 2020 pasando luego a ser media y alta. Los niños bajo 15 años de edad constituyen el grupo menos afectado. El diagnóstico se confirma mediante RT-qPCR. La utilidad del CT (cycle threshold) es discutida. Objetivo: Describir las características epidemiológicas y clínicas de los niños infectados con SARS-CoV-2 y la relación entre el valor del CT y la presentación clínica. METODOLOGÍA: Se realizó un estudio descriptivo, retrospectivo, en pacientes bajo 16 años de edad con infección por SARS-CoV-2, asistidos en un prestador de salud de Montevideo entre la semana epidemiológica (S.E.) 3 del 2020 y la SE 9 del 2021. Se describieron variables clínicas, noción epidemiológica, gravedad y evolución. Se consignó el valor del CT al diagnóstico y se comparó con la presencia de síntomas. RESULTADOS: Los pacientes bajo 16 años representaron el 16,6% del total de infectados (794 en 4.792). El 70% de los casos ocurrió entre los meses de enero y febrero de 2021. El 67,6% presentó contacto intradomiciliario. La media de edad fue 7,5 ± 4,1 años, 51% de sexo masculino. Presentaron síntomas 55% y fueron asintomáticos 45%; no se observaron diferencias significativas en la media, moda y rango de edades de ambos grupos. Ninguno presentó comorbilidades. En el grupo de los 440 pacientes sintomáticos, 55% presentaron fiebre: 32% asociada con otros síntomas, principalmente respiratorios altos y 23% como único síntoma. El valor de CT se obtuvo en 536 de los 794 pacientes (67,5%). La media de CT fue 29,7 ± 5,8 en el grupo de sintomáticos vs. 31,5 ± 5,7 en asintomáticos (p > 0,05). Se hospitalizaron tres pacientes, ninguno requirió cuidados intensivos ni falleció. CONCLUSIONES: La prevalencia e incidencia de la infección por SARS-CoV-2 en niños acompañan a la de adultos y la mayoría cursó formas leves o asintomáticas, sin complicaciones. En esta serie, el valor de CT no fue diferente en niños sintomáticos y asintomáticos. El contacto estrecho intradomiciliario fue la principal fuente de infección.

BACKGROUND: After the detection of the first cases of SARS-CoV-2 and the declaration of a health emergency in the country, community transmission of the virus remained low to moderate until November 2020, later becoming medium and high. Children under 15 years of age constitute the least affected group. The diagnosis is confirmed by RT-qPCR. The usefulness of the CT (cycle threshold) is discussed. AIM: To describe the epidemiological and clinical characteristics of children infected with SARS-CoV-2 and the relationship between the CT value and clinical presentation. METHOD: A descriptive, retrospective study was carried out in patients under 16 years of age with SARS-CoV-2 infection, assisted by a health provider in Montevideo between epidemiological week (EW) 3 of2020 and EW 9 of2021. Clinical variables, epidemiological notion, severity and evolution were described. The CT value at diagnosis was recorded and compared with the presence of symptoms. RESULTS: Patients under 16 years of age represented 16.6% of the total infected (794 in 4,792). 70% of the cases occurred between the months of January and February 2021. 67.6% presented intradomiciliary contact. The mean age was 7.5 ± 4.1 years, 51% were male. 55% presented symptoms and 45% were asymptomatic; no significant differences were observed in the mean, mode and age range of both groups. None presented comorbidities. In the group of 440 symptomatic patients, 55% presented fever: 32% associated with other symptoms, mainly upper respiratory symptoms, and 23% as the only symptom. The CT value was obtained in 536 of the 794 patients (67.5%). The mean CT was 29.7+5.8 in the symptomatic group vs. 31.5 ± 5.7 in asymptomatic patients (p > 0.05). Three patients were hospitalized, none required intensive care and none died. CONCLUSIONS: The prevalence and incidence of SARS-CoV-2 infection in children accompany that of adults and the majority had mild or asymptomatic forms, without complications. In this series, the CT value was not different in symptomatic and asymptomatic children. Close household contact was the main source of infection.

Bilateral orbital inflammation in a 6-month old with SARS-CoV-2 infection.

A 6-month-old female presented with bilateral periorbital edema for 7 days. Laboratory testing was significant for active SARS-CoV-2 infection. Neuroimaging demonstrated soft tissue changes within the bilateral orbits and enlargement of the bilateral lacrimal glands. Although the patient initially improved with corticosteroid treatment, she later returned with recurrent left periorbital and eyelid edema. Orbital biopsy was performed and demonstrated findings in the lacrimal gland and the adjacent fibroconnective tissues that are similar to those of prior lung specimens seen in SARS-CoV-2 patients. Final diagnosis was bilateral orbital inflammation with features presumed secondary to SARS-CoV-2 infection. To the best of our knowledge, this is one of the first reports to document bilateral orbital inflammation as a sign of SARS-CoV-2 infection in the pediatric population with the associated pathological findings.

Defining High-risk Retinoblastoma: A Multicenter Global Survey.

IMPORTANCE: High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. OBJECTIVE: To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. DESIGN, SETTING, AND PARTICIPANTS: An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. INTERVENTION: Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. MAIN OUTCOMES AND MEASURES: High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. RESULTS: Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. CONCLUSIONS AND RELEVANCE: Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

Primary meningococcal arthritis of the hip due to serogroup W in a pediatric patient.

BACKGROUND: Primary meningococcal arthritis (PMA) is defined as the presence of acute septic arthritis with the identification of Neisseria meningitidis in synovial fluid or blood cultures but no clinical evidence of sepsis or meningitis. This report aimed to describe a clinical case of PMA caused by serogroup W, an uncommon etiology of this disease in Uruguay, and review the available literature. CASE REPORT: We report the case of a 5-year-old female, with no past medical history, admitted to the emergency department with a 12-hour history of fever of 39 °C and a limp. The patient was hemodynamically stable and had no clinical evidence of meningitis. Hip ultrasound showed an increase in synovial fluid. Arthrocentesis showed purulent exudate and synovial fluid culture showed no growth after five days. The blood culture showed isolates of N. meningitidis, serogroup W. The patient received treatment with ceftriaxone, and drainage of the affected joint was performed with excellent clinical response. CONCLUSIONS: Primary meningococcal arthritis is a rare presentation of meningococcal disease. Systematic arthrocentesis and the adequacy of antibiotic therapy when septic arthritis is clinically suspected are essential for confirming the diagnosis and decompressive drainage of the involved joint. This report is the first of PMA caused by serogroup W in Uruguay. Although the most common serogroup involved in meningococcal arthritis is serogroup B in Uruguay, an increase in serogroup W-related diseases has been reported in Chile and Argentina, emphasizing the need for epidemiological surveillance.

Malaria importada en niños: primer caso en Uruguay / Imported malaria in children: first case in Uruguay / Malária importada em crianças, o primeiro caso no Uruguai

Resumen: La malaria es un problema de salud a nivel mundial. Si bien en Uruguay existen ejemplares del género Anopheles, las especies descritas con mayor frecuencia no transmiten la enfermedad. Se comunica el primer caso de una niña con malaria importada, no complicada, por Plasmodium falciparum. El objetivo es sensibilizar al pediatra sobre una enfermedad reemergente y analizar su abordaje diagnóstico y terapéutico. Caso clínico: niña de 8 años, sana, procedente de Bolívar (Venezuela). Vive en Uruguay desde hace 15 días. Comienza cinco días previos al ingreso con fiebre de 41 °C, rinorrea y tos seca, vómitos ocasionales en las últimas 24 horas. Anorexia y marcado decaimiento. No lesiones de piel, cefalea, ni artromialgias. Examen físico: decaída, chucho febril, dolor abdominal difuso y hepatoesplenomegalia. Estudios complementarios: anemia, plaquetopenia, elevación de reactantes de fase aguda y de gamma glutamil transferasa. Ecografía abdominal: hepatoesplenomegalia moderada. Estudio parasitológico de sangre periférica: trofozoitos de Plasmodium falciparum, parasitemia menor a 10%. Se administra artemeter-lumefantrina durante tres días, seguido de primaquina por 14 días, con buena evolución. Conclusiones: la malaria debe ser considerada en un niño que proviene de zonas endémicas y se presenta con una enfermedad febril aguda, acompañada de chuchos, decaimiento y hepatoesplenomegalia. El estudio del frotis sanguíneo y gota gruesa realizado por el parasitólogo permitirá confirmar el diagnóstico y definir el abordaje terapéutico. Para disminuir la mortalidad es importante el diagnóstico oportuno y la identificación precoz de signos de malaria grave. El tratamiento será dirigido según la especie involucrada y riesgo de resistencia a los antimaláricos.

Summary: Malaria is a global health problem. Although there are specimens of the genus Anopheles, in Uruguay, the most frequently described species do not transmit the disease. We hereby report the first case of a girl with imported, uncomplicated Plasmodium falciparum malaria. The objective is to raise pediatricians' awareness regarding a re-emerging disease and analyze its diagnostic and therapeutic approach. Clinical case: 8-year-old, healthy girl from Bolívar (Venezuela) who had lived in Uruguay for 15 days. 5 days prior to admission started having 41°C fever, runny nose and dry cough and occasional vomit in the 24 hours prior to admittance. Anorexia and significant asthenia. No skin lesions, headaches or arthromyalgia. Physical exam: asthenia, feverish shivering, diffuse abdominal pain, and hepatosplenomegaly. Complementary studies: anemia, thrombocytopenia, high acute phase reactants and gamma glutamyl transferase. Abdominal ultrasound: moderate hepatosplenomegaly. Parasitological study of peripheral blood: Plasmodium falciparum trophozoites, parasitemia less than 10%. Artemether-lumefantrine was administered for 3 days, followed by primaquine for 14 days, with positive evolution. Conclusions: Malaria should be considered in cases of children from endemic areas who show acute febrile illness, accompanied by shivering, asthenia and hepatosplenomegaly. The study of the thick and peripheral blood smears carried out by the parasitologist will eventually confirm the diagnosis and define the therapeutic approach. In order to reduce mortality, it is essential to carry out a timely diagnosis and to identify symptoms of severe malaria early on. Treatment will depend on the species involved and risk of resistance to antimalarials.

Resumo: A malária é um problema de saúde global. Embora no Uruguai existam exemplares do gênero Anopheles, as espécies mais frequentemente descritas não transmitem a doença. Relatamos o primeiro caso de uma menina com malária importada não complicada por Plasmodium falciparum. O objetivo é sensibilizar o pediatra sobre uma doença reemergente e analisar sua abordagem diagnóstica e terapêutica. Caso clínico: menina saudável de 8 anos, procedente de Bolívar (Venezuela) que tinha morado no Uruguai por 15 dias. 5 dias antes da internação começa a ter febre de 41°C, rinorreia, tosse seca e vômitos ocasionais nas 24 horas anteriores à internação. Anorexia e astenia acentuada. Sem lesões cutâneas, dores de cabeça ou artromialgia. Exame físico: astenia, tremor febril, dor abdominal difusa e hepatoesplenomegalia. Estudos complementares: anemia, plaquetopenia, elevação dos reagentes de fase aguda e gama glutamil transferase. Ultrassonografia abdominal: hepatoesplenomegalia moderada. Estudo parasitológico do sangue periférico: trofozoítos por Plasmodium falciparum, parasitemia inferior a 10%. Administramos artemeter-lumefantrina por 3 dias, seguida de primaquina por 14 dias, com boa evolução. Conclusões: devemos considerar a malária em crianças procedentes de áreas endêmicas e com quadro febril agudo, acompanhado de tremores, astenia e hepatoesplenomegalia. O exame do esfregaço e de gota espessa quando feito pelo parasitologista vai confirmar o diagnóstico e definir a abordagem terapêutica. É importante realizar diagnóstico precoce e identificar os sinais de malária para diminuir o risco de mortalidade. O tratamento será administrado de acordo com a espécie envolvida e com o risco de resistência aos antimaláricos.