Viral Conjunctivitis Rates Unchanged Before and During the COVID-19 Pandemic in an Ophthalmology Clinic.

Background: Millions of acute conjunctivitis cases occur in the United States annually. The impact of COVID-19 mitigation practices on viral conjunctivitis incidence within ophthalmology clinics has not been reported. We hypothesized that viral conjunctivitis rates would decrease with implementation of such practices. Methods: A retrospective chart review was conducted at a single academic center's ophthalmology clinics. Electronic health record data was queried using ICD-10 diagnostic codes to include 649 patients aged 2-97 with viral, bacterial, or allergic conjunctivitis diagnosed either before (6/1/2018-5/1/2019) or during (6/1/2020-5/1/2021) COVID-19 precautions. Conjunctivitis rates per ophthalmology clinic visit were compared using rate-ratio analysis. Logistic regression evaluated the effects of age, sex, and race among those with conjunctivitis. Results: A total of 66,027 ophthalmology clinic visits occurred during the study period. Viral conjunctivitis rates per visit did not significantly change after enacting COVID-19 mitigation strategies, but allergic conjunctivitis rates significantly increased (viral: RR 0.82, 95% CI 0.51 to 1.31, p=0.408; allergic: RR 1.70, 95% CI 1.43 to 2.03, p<0.001). When controlling for time, younger age (≤ median age 55) (p=0.005) and Caucasian race (p=0.009) were associated with higher viral conjunctivitis frequency. Conclusion: Contrary to trends reported in emergency departments, viral conjunctivitis rates within an ophthalmology clinic did not significantly change after COVID-19 mitigation strategies, though allergic conjunctivitis rates increased. Patients' avoidance of emergency departments during the pandemic may have contributed. Further investigation is required to explore variation in ophthalmology patient populations and needs based on care setting.

A retrospective review included 649 patients with viral, bacterial, or allergic conjunctivitis diagnosed at a single center's ophthalmology clinics before (6/1/2018­5/1/2019) or during (6/1/2020­5/1/2021) COVID-19 precautions. Contrary to emergency department experiences, viral conjunctivitis rates did not significantly change after COVID-19 precautions. However, allergic conjunctivitis rates significantly increased. Conjunctivitis presentation in ophthalmology clinics differed from that reported in emergency departments, warranting further evaluation of variation in patient needs by setting.

Ligand-dependent hedgehog signaling maintains an undifferentiated, malignant osteosarcoma phenotype.

TP53 and RB1 loss-of-function mutations are common in osteosarcoma. During development, combined loss of TP53 and RB1 function leads to downregulation of autophagy and the aberrant formation of primary cilia, cellular organelles essential for the transmission of canonical Hedgehog (Hh) signaling. Excess cilia formation then leads to hypersensitivity to Hedgehog (Hh) ligand signaling. In mouse and human models, we now show that osteosarcomas with mutations in TP53 and RB1 exhibit enhanced ligand-dependent Hh pathway activation through Smoothened (SMO), a transmembrane signaling molecule required for activation of the canonical Hh pathway. This dependence is mediated by hypersensitivity to Hh ligand and is accompanied by impaired autophagy and increased primary cilia formation and expression of Hh ligand in vivo. Using a conditional genetic mouse model of Trp53 and Rb1 inactivation in osteoblast progenitors, we further show that deletion of Smo converts the highly malignant osteosarcoma phenotype to benign, well differentiated bone tumors. Conversely, conditional overexpression of SHH ligand, or a gain-of-function SMO mutant in committed osteoblast progenitors during development blocks terminal bone differentiation. Finally, we demonstrate that the SMO antagonist sonidegib (LDE225) induces growth arrest and terminal differentiation in vivo in osteosarcomas that express primary cilia and Hh ligand combined with mutations in TP53. These results provide a mechanistic framework for aberrant Hh signaling in osteosarcoma based on defining mutations in the tumor suppressor, TP53.

Ganglion Cell Layer Thickness Variance Using SPECTRALIS Optical Coherence Tomography.

BACKGROUND: To determine the normal variance of the mean macular ganglion cell layer (GCL) volume among subjects without significant ocular pathology using SPECTRALIS optical coherence tomography (OCT). METHODS: Fifty subjects underwent a baseline scan using SPECTRALIS OCT followed by 2 more studies with (reg-ON) and without (reg-OFF) eye registration all taken at the same session. The mean GCL volume was measured using built-in SPECTRALIS software. Eyes with macular pathology were excluded. The reproducibility of the measurements of the GCL volume was evaluated with Bland-Altman plots and limits of agreement, intraclass correlation coefficient (ICC), and the coefficient of repeatability (CR). RESULTS: A total of 98 eyes met criteria for the analysis. The mean GCL volume difference was 0.0002 ± 0.029 and -0.0005 ± 0.035 mm 3 for scans 1 versus 2 (baseline vs reg-ON) and 3 (baseline vs reg-OFF), respectively. The ICCs were 0.985 and 0.977 for the baseline vs reg-ON and reg-OFF groups. The CR for baseline vs reg-ON was 0.056 while CR for baseline vs reg-OFF was 0.069. Ninety percent of eyes fell within 0.04 mm 3 of test-retest reliability. CONCLUSIONS: Our model found a predictable threshold of 0.07 mm 3 or less for SPECTRALIS OCT mean GCL volume variance, which did not significantly change with eye registration in eyes without macular pathology. Clinicians may also consider a threshold of 0.04 mm 3 when determining stable vs progressive changes in mean GCL volume using this device.

Paroxysmal Cold Hemoglobinuria: Diagnosis From the Blood Smear.

Phagocytosis of red cells by neutrophils, referred to as neutrophil erythrophagocytosis, on the blood smear as a helpful diagnostic sign of paroxysmal cold hemoglobinuria is underrecognized. We present a child with paroxysmal cold hemoglobinuria and prominent neutrophil erythrophagocytosis to highlight the importance of this finding in the diagnosis of paroxysmal cold hemoglobinuria.

Clinical Characteristics of Idiopathic Intracranial Hypertension in Patients Over 50 Years of Age: A multicenter clinical cohort study.

PURPOSE: To characterize the clinical features of idiopathic intracranial hypertension (IIH) in patients >50 years of age compared to the typical IIH population and existing data for this older cohort. DESIGN: Retrospective, clinical cohort study. METHODS: Medical records of 65 patients >50 years of age at first diagnosis of IIH were reviewed based on the Modified Dandy Criteria from 4 academic centers. Each center provided randomly selected controls from IIH patients <50 years of age for each study patient at their location. Data recorded included patient demographics, presenting symptoms, medications, coexisting medical conditions, cerebrospinal fluid (CSF) opening pressure, treatments, and neuro-ophthalmic data from initial and final visits. RESULTS: Compared to controls, the older cohort showed the following characteristics: fewer females (n = 51 [78.5%] vs. controls: n = 60 [92.3%]; P = .045), fewer headaches (n = 33 [50.8%] vs. controls: 52 [80.0%]; P = .001), more frequent incidental discoveries of papilledema (n = 19 [29.2%] vs. controls: 7 [10.8%]; P = .015), and lower CSF opening pressure [median: 33 cm H2O [range: 21-58 cm H2O] vs. the median for controls: 34 cm H2O [range: 24-67 cm H2O; P = .029). CONCLUSIONS: Patients with IIH diagnosed at >50 years of age were less often female and had lower CSF opening pressure, fewer headaches, a higher chance of incidentally identified papilledema, and body mass index similar to that of younger IIH patients. Older IIH onset was not associated with worse visual outcome.

Sleep and fatigue in pediatric oncology: A review of the literature.

Cancer in children has detrimental effects on sleep patterns and sleep quality, which in turn impacts on the perception of, and the ability to cope with, the emotional and physical challenges associated with both the disease and its treatment. This places an added burden on their quality of life that can last many years beyond diagnosis and treatment. In addition to the effect of the cancer itself, surgery, chemotherapy and radiotherapy can all contribute both short and long term to sleep disruption. Sleep disorders have also been associated with pain, fatigue, medication and hospitalisation in children suffering from cancer. This review will explore the relationship between childhood cancer and associated sleep disorders, in the acute stage of diagnosis, during treatment and in the years following. We will discuss the possible causes and the current treatment modalities used to treat sleep disorders in children with cancer, and in childhood cancer survivors. It has been estimated that the recent advances in treatment have improved the overall five year survival rate for all childhood cancers to over 80%, with some cancers achieving a near 100% cure rate such as early stage Wilms' tumour. Thus, recognition and appropriate treatment of associated sleep disorders is essential to optimise long term quality of life.

ANZCCSG BabyBrain99; intensified systemic chemotherapy, second look surgery and involved field radiation in young children with central nervous system malignancy.

BACKGROUND: ANZCCSG BabyBrain99 is a trial of intensive systemic chemotherapy with dual stem cell supported treatment, second look surgery and involved field radiation for children less than four years of age with malignant central nervous system tumours. PROCEDURE: Following primary resection, treatment included two courses of cisplatin and oral etoposide, a third course of mobilising chemotherapy (vincristine, etoposide, cyclophosphamide) with stem cell harvest, followed by intensive stem cell supported chemotherapy with high dose cyclophosphamide, etoposide and vincristine. Children were evaluated for second resection before proceeding to a second stem cell supported consolidation therapy consisting of melphalan and carboplatin. Patients then received involved field radiation therapy. RESULTS: Thirty three children with a range of diagnoses were enrolled. Nine percent of children had metastatic disease at diagnosis. Eighteen children completed treatment including irradiation. At the end of induction the event free survival was 70% (54-86). Forty eight percent of children had a complete response, 18% had stable disease and 3% had a partial response. Five year overall survival was 40% (22-56) and event free survival was 33% (17-50). Children in whom a complete resection were achieved had a significantly superior outcome compared to those children without a complete resection, 5 year EFS 60% (45-75), as compared to 22% (13-30), P-value <0.05. CONCLUSIONS: BabyBrain99 confirms that intensive stem cell supported chemotherapy can be safely administered to infants with CNS tumours however overall prognosis remains poor. Importantly, the study reinforces a complete surgical resection as an important favourable prognostic indicator. Pediatr Blood Cancer 2011;56:1055-1061. © 2011 Wiley-Liss, Inc.

Hyperhaemolysis in sickle cell disease--an unusual and potentially life-threatening complication.

As sickle cell disease is increasing in Australia, paediatricians and other health care providers need to be aware of the broad range of complications that can occur in this condition. Although the complications of splenic sequestration and chest crises are well recognised, the infrequent but equally dramatic complication of hyperhaemolysis is less well appreciated. Here, we report a case of hyperhaemolysis in a Victorian paediatric patient.

Temozolomide in pediatric low-grade glioma.

BACKGROUND: We describe a retrospective series of children with low-grade glioma who received temozolomide. PROCEDURE: Eligible patients had had a diagnosis of low-grade glioma with or without histological confirmation. Temozolomide was administered at a dose of 200 mg/m(2) daily for 5 days, in a 4-week cycle. Therapy was stopped on completion of the targeted 12 cycles of chemotherapy or on evidence of tumor progression. RESULTS: Thirteen eligible patients were identified, eight male and five female. Median age at diagnosis was 5.5 years (range 2.6-15.0 years) and at commencement of temozolomide treatment was 9.0 years (range 3.8-15.2 years). Nine patients had a histological diagnosis of pilocytic astrocytoma. Twelve patients had received carboplatin prior to temozolomide, including three in combination with vincristine. A total of 111 cycles of therapy have been administered. Hematological toxicity and nausea were the most common adverse effects. Median time to progression was 6.7 months (range 1.5-41.8 months). Event-free survival rate at 3 years was 57%. Twelve of 13 patients remain alive at the time of report. Eleven have stable disease (SD). CONCLUSION: Temozolomide appears to be active in pediatric low-grade glioma, with the advantage of oral administration and excellent tolerability.

Adverse hypersensitivity reactions to mesna as adjunctive therapy for cyclophosphamide.

Mesna is widely used for the prevention of cyclophosphamide-related hemorrhagic cystitis. It has been associated with hypersensitivity-like cutaneous and systemic reactions in adult patients. We report a series of children with malignant disease, who developed such reactions following mesna administration and discuss possible mechanisms and management issues.

Megestrol acetate in pediatric oncology patients may lead to severe, symptomatic adrenal suppression.

BACKGROUND: Despite the widespread use of megestrol acetate (MA) among a growing number of pediatric oncology departments, there is only one published study on the use of MA in children with malignant disease. The objectives of the current study were to examine the effect of MA in improving the nutritional status of children with malignant disease and to describe and consider the implications of MA-associated adrenal suppression that was found consistently. METHODS: Medical records of 19 children with malignant disease who were treated with MA were reviewed. During MA therapy, clinical assessments every 4 weeks included anthropometrics, caloric intake, quality-of-life scores, and appetite scores. Serum cortisol levels, lipid profiles (including cholesterol levels) random blood glucose levels, and coagulation screening were measured at 4-6-week intervals. RESULTS: MA use was associated with significant increases in weight, weight z score, middle-upper arm circumference, triceps skin-fold thickness, appetite, and caloric intake. MA was extremely useful in aiding the efficient tapering of nasogastric feeds. However, a significant and potentially dangerous decrease in cortisol was seen in 10 of 11 patients tested, with 1 patient who manifested clinical hypoadrenalism with hemodynamic collapse, requiring inotropic support. This is the first report of MA-associated clinical adrenal suppression in a child with malignant disease. CONCLUSIONS: Although the results of this study support the ability of MA to improve nutritional status, its use was complicated by severe adrenal suppression in almost all patients tested, with a serious clinical adverse event occurring in one patient. Routine hydrocortisone supplementation throughout MA treatment should be considered as well as larger doses for patients with acute illness and patients who undergo surgery.