Bilateral Eyelid Edema in a Pediatric Patient With COVID-19: A Case Report and Literature Review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is primarily transmitted through the eyes, nose, or mouth. Ophthalmic complications, such as conjunctivitis and dacryoadenitis, have been reported in patients with coronavirus disease 19 (COVID-19). We report the case of an early adolescent girl who presented with bilateral urticarial rashes, eyelid edema, fever, and cough. She was diagnosed with acute dacryoadenitis with SARS-CoV-2 infection confirmed by a nasopharyngeal polymerase chain reaction and clinical investigations. The patient was treated with dexamethasone (3 mg daily) for three days, which resulted in the resolution of fever and urticarial rash, and improvement of eyelid edema. While bilateral upper eyelid edema and acute dacryoadenitis commonly occur in pediatric patients due to Epstein-Barr virus (EBV) infection and Kawasaki disease, they are rarely associated with other diseases. However, ocular symptoms have been reported in 11.4% of patients with COVID-19. In addition, eyelid edema and acute dacryoadenitis have also been reported after COVID-19 messenger RNA (mRNA) vaccination. The underlying mechanisms of these complications are not yet completely understood. Our case highlights the possibility of bilateral eyelid edema in children with COVID-19, which can occur in addition to other viral infections such as EBV.

CDK actively contributes to establishment of the stationary phase state in fission yeast.

Upon exhaustion of essential environmental nutrients, unicellular organisms cease cell division and enter stationary phase, a metabolically repressed state essential for cell survival in stressful environments. In the fission yeast Schizosaccharomyces pombe, cell size is reduced by cell division before entry into stationary phase; thus cyclin-dependent kinase (CDK) must actively contribute to stationary phase establishment. However, the contribution of CDK to stationary phase remains largely uncharacterized. Here, we examine the role of the sole S. pombe CDK, Cdc2, in the establishment of stationary phase. We show that in stationary phase, nuclear and chromosomal volumes and the nucleus-to-cell volume ratio are reduced, and sister chromatid separation and chromosome fluctuation are repressed. Furthermore, Cdc2 accumulates in the nucleolus. Most of these changes are induced by glucose depletion. Reduction in Cdc2 activity before and upon stationary phase entry alleviates the changes and shortens the survival time of stationary phase cells, whereas Cdc2 inhibition represses nucleolar Cdc2 accumulation and glucose depletion-induced nuclear volume reduction. These results demonstrate that CDK actively regulates stationary phase, both before and upon stationary phase entry.

Detection of Histidine-Tagged Protein in Escherichia coli by Single-Cell Inductively Coupled Plasma-Mass Spectrometry.

We have developed a rapid and precise quantification method for a histidine (His)-tagged recombinant protein produced in Escherichia coli (E. coli) by single-cell inductively coupled plasma-mass spectrometry (SC-ICP-MS). Plasmid vector containing enhanced green fluorescent protein (EGFP) or red fluorescent protein (mCherry) gene fused with His-tag was transformed into E. coli. The transformed E. coli was exposed to nickel (Ni) chloride or cobalt (Co) chloride for labeling His-tag with the Ni or Co ion. Then, E. coli was analyzed by SC-ICP-MS to determine the amount of EGFP or mCherry protein on the basis of the signal of Ni or Co bound to His-tag. By comparing Ni and Co contents in E. coli expressing His-tagged mCherry with those in nontagged mCherry, the specific binding of Co to His-tag was more clearly detected than that of Ni. The Co contents were increased until 6 h after the protein induction, and this observation was coincident with the increases in fluorescence intensity of EGFP or mCherry measured by a flow cytometer. However, the Co contents were decreased for EGFP and kept at a constant level for mCherry from 6 to 24 h despite the continuous increase in the fluorescence intensity through incubation. The fluorescent proteins were mainly recovered in the insoluble fraction 24 h after the induction. This can be explained by the fact that the overexpressed fluorescent proteins with His-tag are transferred into inclusion bodies, which hampers the binding of the fluorescent proteins to the Co ion. SC-ICP-MS can be a useful technique to precisely quantify soluble recombinant proteins in E. coli without the extraction and purification process.

Autoimmune thyroid disease following hematopoietic stem cell transplantation in childhood cancer survivors.

Thyroid dysfunction has been observed in childhood cancer survivors (CCSs) who have undergone hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed the thyroid function of 54 CCSs who underwent HSCT and were referred to our endocrinology department at Chiba Children's Hospital between January 1, 2008, and December 31, 2019. Three patients developed autoimmune thyroid disease (AITD) after HSCT. Two of these patients had Graves' disease (GD), and the third had autoimmune thyroiditis. The association between HSCT and AITD remains unclear. All three patients had chronic graft versus host disease (GVHD). AITD was reported to be induced by the transmission of abnormal T or B lymphocyte clones from the donor to the recipient. One patient with GD was treated with a high dose of anti-thymocyte globulin (ATG). Some studies have reported that ATG is associated with a risk of severe T cell depletion and GD onset. In conclusion, CCSs who received HSCT rarely developed AITD. We suggest that CCSs treated with ATG and/or experiencing an onset of chronic GVHD should be carefully monitored for thyroid function because it might reveal AITD.

Elevation of serum fibroblast growth factor 23 level in a pediatric patient with lupus nephritis.

Fibroblast growth factor 23 (FGF-23), a hormone mainly secreted by osteocytes and osteoblasts, regulates phosphate and vitamin D levels. However, the in vivo significance of FGF-23 is not fully elucidated. This case report describes a 12-year-old girl with systemic lupus erythematosus (SLE), lupus nephritis, and an elevated serum FGF-23 level. The patient was treated with active vitamin D and oral sodium phosphate medications to manage low serum phosphate levels (2.2 mg/dL). Magnetic resonance imaging (MRI) revealed a high-intensity area in the left femur, but somatostatin receptor scintigraphy images did not indicate tumor-induced osteomalacia. SLE treatment using mycophenolate mofetil (1500 mg/day) was initiated, and serum complements levels increased as FGF-23 level increased. Serum FGF-23 level gradually decreased as urinary protein levels decreased after treatment with steroids; however, there was no change in the high-intensity area on MRI. Recent studies have reported that serum FGF-23 level is associated with iron deficiency and inflammation; yet, the mechanism related to these associations is not fully elucidated. The findings from this case suggest that elevated serum FGF-23 levels noted in our patient were related to silent lupus nephritis and lupus nephritis activity.

Acute kidney injury caused by ammonium acid urate crystals in diabetic ketoacidosis at the onset of type 1 diabetes mellitus.

SUMMARY: Ammonium acid urate (AAU) crystals are rare in industrialized countries. Furthermore, the number of children with diabetic ketoacidosis (DKA) who develop severe acute kidney injury (AKI) after hospitalization is small. We encountered two patients with AKI caused by AAU crystals during the recovery phase of DKA upon admission. They were diagnosed with severe DKA and hyperuricemia. Their urine volume decreased and AKI developed several days after hospitalization; however, acidosis improved in both patients. Urine sediment analysis revealed AAU crystals. They were treated with urine alkalization and diuretics. Excretion of ammonia in the urine and urine pH levels increased after treatment of DKA, which resulted in the formation of AAU crystals. In patients with severe DKA, the urine and urine sediment should be carefully examined as AAU can form in the recovery phase of DKA. LEARNING POINTS: Ammonium acid urate crystals could be formed in the recovery phase of diabetic ketoacidosis. Diabetic ketoacidosis patients may develop acute kidney injury caused by ammonium acid urate crystals. Urine and urine sediment should be carefully checked in patients with severe DKA who present with hyperuricemia and volume depletion.

Factors predicting endocrine late effects in childhood cancer survivors from a Japanese hospital.

We retrospectively analyzed endocrine late effects in 81 childhood cancer survivor (CCS) patients who had been referred to our endocrinology department in Chiba Children's Hospital between January 1, 2008 and December 31, 2016. Among 69 eligible patients (33 male, 36 female), endocrine late effects were identified in 56 patients (81.1%). The median age at the last visit to our endocrinology department was 17.4 years (range: 7.1-35.3 years). The most common primary cancer was acute lymphoblastic leukemia (22 patients, 31.8%). Forty-four patients (64%) were treated using radiation therapy. A primary brain tumor and high doses (≥6 g/m2) of cyclophosphamide were significantly associated with growth hormone deficiency (GHD). Our present study suggests that high doses of cyclophosphamide is a risk factor for GHD. Adult heights and pubertal growth spurts of patients treated with radiation therapy were significantly lower than patients not treated with radiation therapy. Our retrospective study reconfirmed that hematopoietic stem cell transplantation and chronic graft versus host disease (GVHD) were associated with elevated risks of primary hypothyroidism. However, it is unclear whether GVHD induces thyroid dysfunction. Gonadal radiation and busulfan were associated with primary hypogonadism as reported in previous studies. We found high doses of cyclophosphamide to be involved in pituitary disorders. We suggest that pediatric endocrinologists should discuss the potential effects of radiation therapy on adult height and pubertal growth spurt in CCS patients. Moreover, patients who have been treated with high doses of cyclophosphamide or have chronic GVHD require long-term follow-up for endocrine late effects.

Thyroid nodules and long-term follow-up among childhood cancer survivors who underwent hematopoietic stem cell transplantation.

Thyroid nodules have been observed in childhood cancer survivors (CCS) treated with chemotherapy and radiotherapy. We report four patients with thyroid nodules identified during the long-term follow-up of children who underwent hematopoietic stem cell transplantation (HSCT). The thyroid nodules were diagnosed as adenomatous goiter in all four patients. The interval between the primary cancer diagnosis and the occurrence of the thyroid nodules was more than 10 yr. Furthermore, all four patients underwent HSCT in conditioning with total body irradiation (TBI) before the age of 10 yr. Two of four patients commenced treatment with levothyroxine due to elevated TSH levels. Only two patients showed elevated thyroglobulin levels (> 70 µg/L). In conclusion, we suggest that CCS who have undergone HSCT in conditioning with TBI more than 10 yr previously should be followed up carefully for thyroid nodules using ultrasound.