Biallelic TMEM251 variants in patients with severe skeletal dysplasia and extreme short stature.

Skeletal dysplasias are a heterogeneous group of disorders ranging from mild to lethal skeletal defects. We investigated two unrelated families with individuals presenting with a severe skeletal disorder. In family NMD02, affected individuals had a dysostosis multiplex-like skeletal dysplasia and severe short stature (<-8.5 SD). They manifested increasingly coarse facial features, protruding abdomens, and progressive skeletal changes, reminiscent of mucopolysaccharidosis. The patients gradually lost mobility and the two oldest affected individuals died in their twenties. The affected child in family ID01 had coarse facial features and severe skeletal dysplasia with clinical features similar to mucopolysaccharidosis. She had short stature, craniosynostosis, kyphoscoliosis, and hip-joint subluxation. She died at the age of 5 years. Whole-exome sequencing identified two homozygous variants c.133C>T; p.(Arg45Trp) and c.215dupA; p.(Tyr72Ter), respectively, in the two families, affecting an evolutionary conserved gene TMEM251 (NM_001098621.1). Immunofluorescence and confocal studies using human osteosarcoma cells indicated that TMEM251 is localized to the Golgi complex. However, p.Arg45Trp mutant TMEM251 protein was targeted less efficiently and the localization was punctate. Tmem251 knockdown by small interfering RNA induced dedifferentiation of rat primary chondrocytes. Our work implicates TMEM251 in the pathogenesis of a novel disorder and suggests its potential function in chondrocyte differentiation.

Case reports of invasive mucormycosis associated neutropenic enterocolitis in leukemic children: diagnostic and treatment challenges and review of literature.

BACKGROUND: Bacterial enterocolitis is one of the most common neutropenic fever complications during intensive chemotherapy. Despite aggressive antibacterial treatments, this complication usually imposes high morbidity and mortality in cancer patients. Management of bacterial neutropenic enterocolitis are well known; however, management of fungal neutropenic enterocolitis may be more challenging and needs to be investigated. Prompt diagnosis and treatment may be life-saving, especially in patients at risk of mucormycosis-associated neutropenic enterocolitis. CASE PRESENTATION: We report two mucormycosis-associated neutropenic enterocolitis cases in pediatric leukemic patients receiving salvage chemotherapy for disease relapse. Both patients' clinical signs and symptoms differ from classical bacterial neutropenic enterocolitis. They were empirically treated as bacterial neutropenic enterocolitis with anti-gram-negative combination therapy. Despite broad-spectrum antimicrobial treatment, no clinical improvement was achieved, and both of them were complicated with severe abdominal pain necessitating surgical intervention. Mucormycosis is diagnosed by immunohistopathologic examination in multiple intraoperative intestinal tissue biopsies. Both patients died despite antifungal treatment with liposomal amphotericin-B and surgical intervention. CONCLUSION: Mucormycosis-associated neutropenic enterocolitis is one of the most unfavorable and untreatable side effects of salvage chemotherapy in leukemic children with disease relapse. This report could be of considerable insight to the clinicians and scientists who counter the enigma of fungal infections during febrile neutropenia and help to understand better diagnosis and management.

Impact of the COVID-19 Pandemic on the Success of Bariatric Surgeries in Patients with Severe Obesity.

INTRODUCTION: SARS-CoV-2 infection (COVID-19) pandemic may influence the weight outcomes of bariatric surgeries (BS). Here, we intended to compare the weight outcome of patients who underwent BS before and during the pandemic time. METHODS: In a retrospective, single-center study, the information of two groups of patients; first COVID-19 group (n = 51) consisted of those that underwent BS during the pandemic and completed a year of follow-up, second non-COVID-19 group included 50 patients who underwent BS and were followed up before the pandemic. All the patients' anthropometric and obesity-related disease data were compared between groups. RESULTS: Weight loss and the decrease of body mass index 1 year after the surgery, as well as excess weight loss and total weight loss, were significantly higher in the non-COVID-19 group compared to the COVID-19 group (p < 0.05). Although the rate of remission for diabetes mellitus, hypertension, and dyslipidemia was higher in the non-COVID-19 group, the differences were not statistically significant (p > 0.05). CONCLUSION: We showed a significantly poorer weight outcome at the 1-year follow-up of the BS during the pandemic compared to the pre-pandemic. These results need further investigations to determine the preventive measures and management by evaluating the associated factors.

A Systematic Review and Meta-Analysis of Vitamin D Status of Patients with Severe Obesity in Various Regions Worldwide.

INTRODUCTION: Managing nutritional deficiencies is an essential component in the treatment of severe obesity. Vitamin D deficiency is often reported in investigations in severely obese cohorts. However, no prior study has summarized findings on this topic. Consequently, the aim of this systematic review and meta-analysis was to investigate the 25-hydroxyvitamin D [25(OH)D] status in individuals with severe obesity in different regions worldwide. We also evaluated levels of calcium, parathyroid hormone (PTH), and magnesium as secondary outcome measures. METHODS: We searched Medline, PubMed, Scopus, the Cochrane Library, and EMBASE for relevant observational studies published in English from 2009 to October 2021. The heterogeneity index among the studies was determined using the Cochran (Q) and I2 tests. Based on the heterogeneity results, the random-effect model was applied to estimate the prevalence of vitamin D deficiency. RESULTS: We identified 109 eligible observational studies. Overall, 59.44% of patients had vitamin D deficiency [25(OH)D <20 ng/mL], whereas 26.95% had vitamin D insufficiency [25(OH)D 20-30 ng/mL]. Moreover, the mean 25(OH)D level was 18.65 ng/mL in 96 studies. The pooled mean estimate of the serum calcium, PTH, and magnesium was 9.26 mg/dL (95% confidence interval [CI]: 9.19-9.32, I2 = 99.7%, p < 0.001), 59.24 pg/mL (95% CI: 54.98, 63.51, I2 = 99.7%, p < 0.001), and 0.91 mg/dL (95% CI: 0.84, 0.98, I2 = 100.0%, p < 0.001), respectively. The results of the subgroup analysis indicated that the mean estimates of 25(OH)D were highest in North America (21.71 ng/mL [19.69, 23.74], [I2 = 97.2%, p < 0.001]) and lowest in Southeast Asia (14.93 ng/mL [14.54, 15.33], [I2 = 0.0%, p = 0.778]). CONCLUSION: The results obtained showed a significant prevalence of vitamin D deficiency among severely obese individuals in various geographical regions, whereas the highest and lowest mean estimates were reported for North America and Southeast Asia, respectively.

Utilization of chest tube as an esophagus stent in pediatric caustic injuries: A retrospective study.

BACKGROUND: The management of caustic esophageal burns in the pediatric population has changed over the years, while the most optimal management with regards to effectiveness, availability, and cost-beneficent stays controvertible. AIM: To describe how to utilize a chest tube for esophageal stenting in pediatrics. METHODS: Data regarding the etiology, treatment, and complications of caustic injury in pediatrics over 10 years was collected retrospectively. Furthermore, data regarding the patient's follow-up who underwent esophageal chest tube (ECT) were collected. The ECT was prepared by carving a narrowed section in the chest tube while maintaining the radiopaque section. The ECT will then be positioned from the cricopharyngeal and exited through the nostril and fixed on the patient's cheek. RESULTS: During the period of our study, data from 57 patients with an average age of 2.5 years (range 1-12; SD = 1.7) were obtained. The results showed that 89% of esophageal injury was due to alkaline and 9.4% were caused by acidic agents. The treatment methods showed that 29 patients (50.8%) recovered with dilatation alone. In 16 patients (28.06%), the esophageal repair was performed by using the colon, and in 5 patients (8.7%), other surgical methods were used and in 7 patients (12.2%), the ECT stents were used. ECT was inserted in 7 cases with a mean age of 2 (range: 1.5-3) years who were classified as grade IIB or III. Grading was performed by endoscopy assessment on the first day. Antibiotics and corticosteroids were administrated as initial medical management for all patients. ECT implantation was done during the first 8 d for 5 out of 7 cases (mean: 3.8 d). For the 2 patients, ECT was used after 27 (patient 6) d and 83 (patient 7) d. The reason for late stenting in these patients was a postponed referral to our center, in which patient 7 even received 4 dilation episodes before visiting our center. ECT was removed after an average of 44 d in the first 5 patients, while in the other 2 patients (6 and 7) was 2 and 1 wk, respectively. There was no complication related to, or failure of, stent placement. It is worth mentioning that none of the 7 ECT cases required gastrostomy or jejunostomy. CONCLUSION: The ECT method introduced in our study can be used as a broadly available, economic, and easy-use facility for esophageal stenting, particularly in developing countries and emergency departments which have limited access to modern equipment. Further multicenter studies with higher volume patients are required for further deployment of this method.

Cellular mesoblastic nephroma in infants and children: Report of four cases and review of the literature.

BACKGROUND: Cellular mesoblastic nephroma is rare after infancy, and there are many controversial reports about its clinical presentation and treatment as well as outcome in infants, young children, and adolescents. OBJECTIVES: In this report, we will discuss our experience with four cases of cellular mesoblastic nephroma presented from infancy to childhood (from 18 months of age to 11 years of age). CASES: During 10 years, we had the experience of 4 cases of pediatric renal tumor with the diagnosis of cellular mesoblastic nephroma, which have been followed between 1 year and 6 years. There were three male and one female patients with the age of 1.5, 2, 2, and 11 years. These tumors showed variable characteristics according to the number of mitosis, proliferative rate, necrosis, immunohistochemical markers, and metastatic potential; however, despite of all of these variabilities, all of these patients have done well and all have been well at the end of study. CONCLUSION: Pediatric renal tumors with the histologic diagnosis of cellular mesoblastic nephroma have good outcome even with metastasis, mitosis, and high proliferative rate.

Immunohistochemical study of enteric nervous system in hirschsprung's disease and intestinal neuronal dysplasia.

BACKGROUND: Hirschsprung's disease (HD) is one of the most common motility disorders in pediatric age groups and it is very important that it be differentiated from other types of motility disorders, especially intestinal neuronal dysplasia B (IND B). Although many studies regarding the differences between the two disorders by immunohistochemical studies exist, there is as yet no consistent result. The purpose of this research was to study the immunohistochemical findings of enteric nervous system in these two motility disorders in comparison with colectomies without motility disorder. METHODS: Full wall thickness specimens of three groups of patients (HD, IND B and non motility disorders) were included in the study to be evaluated by immunohistochemistry (IHC). Markers were specific for neuronal cells and pace maker cells composed of PGP 9.5, c-kit, synaptophysin, S100 and CD56. The number of cells was evaluated in the muscularis properia, and myenteric plexus. RESULTS: The number of all the IHC markers i.e. PGP9.5, c-kit, synaptophysin, S100 and CD56 was completely different in HD from the two other groups, while IND B was quite similar to control group. CONCLUSION: Our finding suggests that there is a marked and significant difference between HD and IND B by IHC markers, which can be used as an additional test for the diagnosis of HD with more accuracy. Further multicenter studies with a greater number of cases would be necessary to find a cut-off point for every IHC marker to differentiate HD and IND B.

Nested stromal epithelial tumor of liver presenting with Cushing syndrome: a rare case report.

Nested stromal and epithelial tumor of the liver is an extremely rare pediatric hepatic tumor. To the best of our knowledge, about 25 cases have been reported in the English literature so far, few of which accompanied with Cushing syndrome. Herein we report our experience with an 8-year-old boy presented with Cushing's syndrome because of ectopic ACTH production by this tumor.

Intrathoracic lipoblastoma in a 15-month-old infant.

Lipoblastoma is a rare tumor of infancy. It originates from the white fetal fat in soft tissue. The most common location of this rare tumor is extremity and to best of our knowledge less than 10 cases of intrathoracic and mediastinal lipoblastoma has been reported in the English literature. Herein we present our experience with a 15-month-old boy infant who presented with severe dyspnea. Imaging studies showed a mass in the thoracic cavity and mediastinum which was diagnosed as lipoblastoma after pathologic examination of the resected mass. Lipoblastoma has been considered as a tumor of soft tissue, but it should also be considered as a rare cause of intrathoracic masses of young children.

Intrapulmonary solitary fibrous tumor with bronchial involvement: a rare case report in a child.

Intrapulmonary solitary fibrous tumor is a very rare neoplasm. Our review of the English literature suggests that it has not previously been reported in children younger than 10 years. Herein, the occurrence of such a rare lesion invading the tracheobronchial tree is reported in a 7-year-old boy.

Pathology of pediatric liver tumors, a single center experience from south of Iran.

BACKGROUND: Pediatric hepatic malignancies are rare, accounting for 1-4% of all solid childhood tumors. The histopathology of childhood hepatic tumors guides the treatment and prognosis, and is the cornerstone for precise diagnosis. Until now, there has been no documented study on pediatric liver tumor cases from this center; in this report, we show our experience about the common types of childhood hepatic tumors during five years (2002-2007) and compare them with other studies. MATERIALS AND METHODS: During five years (2002-2007), all the hepatic tumors of childhood (under 18 year-old) from the pathology file of Namazi Hospital of Shiraz University of Medical Sciences are recorded. This includes both resected specimens and biopsies. All the slides were reviewed and the pathologic diagnosis was confirmed. RESULTS: We detected 53 liver tumor cases in children (below 18 years of age). Among these tumors, 36 (67.9%) were malignant. Male to female ratio was 1.5 to 1. Hepatoblastoma was the most common liver tumor in this age group accounting for 22 patients (41.5%). The second most common primary tumor was hepatocellular carcinoma (HCC), with five patients. Another malignant tumor was embryonal sarcoma. Benign tumors included adenoma, mesenchymal hamartoma, vascular tumors, focal nodular hyperplasia, and inflammatory pseudo tumor. There were also seven metastatic tumors during these five years. CONCLUSIONS: The spectrum of hepatic tumors in children is different from that found in the older age group (adults) and also different in different populations.

Malignant epithelioid hemangioendothelioma of the bladder: the first case report in a child.

Epithelioid hemangioendothelioma is a distinct vascular tumor, which is very rare in the bladder. To the best of our knowledge, only one adult patient has been reported so far in the English literature. A 4-year-old boy with a huge bladder mass, with the pathologic diagnosis of epithelioid hemangioendothelioma, is the first patient with this lesion described in the pediatric age-group.