Uncovering p53 Mutations and Abnormal Gene Expression in Pediatric Adrenocortical Cancer

Pediatric adrenocortical cancer is extremely rare and often fatal (approximately 0.3-0.4 cases per million worldwide; 50% 5-year survival). The incidence of pediatric adrenocortical cancer in southern Brazil is 10-15 times higher than the worldwide incidence. Due to the rarity of adrenocortical cancer, especially in children, underlying gene dysregulation and mechanisms of tumorigenesis of the adrenal gland are very poorly described in the literature. However, it is well-known that the tumor suppressor p53, which is mutated in over 50% of all human cancers, is commonly mutated in pediatric adrenocortical cancer. In addition, evidence strongly suggests that if a child has adrenocortical cancer, it indicates a germline p53 mutation exists. In order to provide an understanding of the etiology and the biology of this disease, blood and tumor samples from 35 pediatric adrenocortical tumor patients, including 24 from southern Brazil, were screened for p53 mutations. Matched blood and tumor samples were obtained as available. Of the 35 patient samples screened, 24 samples were entered into a novel gene expression study that exclusively investigated gene dysregulation in pediatric adrenocortical cancer; the first study of its kind. Overall findings from this study reveal the importance of screening for germline p53 mutations and provide fundamental insight into pediatric adrenocortical cancer

Single Center Outcomes of Status Epilepticus at a Paediatric Intensive Care Unit

Background: Status epilepticus (SE) is a frequent admission diagnosis to paediatric intensive care units (PICUs) and is associated with variable outcomes. We have audited our experience of patients presenting in SE at a Canadian PICU to determine unfavorable outcome variables. Methods: Charts of patients \u3c18 years of age presenting in SE to a tertiary care PICU over a 10-year period were audited. Data were analyzed at three care-points: transport, the emergency department (ED) and the PICU. Patient outcome before PICU discharge was categorized as favorable for return to pre-status functioning level or unfavorable for new deficit/death. Student\u27s t-test and the Kruskal-Wallis test were used for analysis of normal and skewed continuous variables, respectively, and either Chi-square test or Fisher\u27s exact test for categorical variables. Results: 189 patients (54% males) were identified with a median age of 1.9 years. Idiopathic SE had the highest incidence; infectious/vascular etiologies were associated with more unfavorable outcomes. Progression to refractory SE in the ED had a higher incidence of death (p\u3c0.05). Patients with an unfavorable outcome had a higher incidence of apnea during transport (p=0.01), longer hospital stays (p\u3c0.05), need for therapeutic coma (p=0.01), longer duration of therapeutic coma (p\u3c0.05), need for mechanical ventilation (p\u3c0.05), and recurrent or refractory seizures during inpatient stay (p\u3c0.05). Multivariate analysis of unfavorable outcomes of patients in SE presenting to the PICU included renal failure, cerebral edema, apnea during transport, refractory seizures, and recurrent seizures. Conclusions: Refractory seizures in children presenting with SE are associated with worsened outcomes in the PICU

Clinical Risk Factors For Central Line Associated Venous Thrombosis (CLAVT) In Children

ABSTRACTBackground: Identifying risk factors related to Central Venous Line (CVL) placement could potentially minimize Central Line-Associated Venous Thrombosis (CLAVT). We sought to identify the clinical factors associated with CLAVT in children. Methods: Over a 3-year period, 3,733 CVLs were placed at a tertiary-care children’s hospital. Data were extracted from the electronic medical records of patients with clinical signs and symptoms of venous thromboembolism (VTE), diagnosed using Doppler ultrasonography and/or echocardiography. Statistical analyses examined differences in CLAVT occurrence between groups based on patient and CVL characteristics (type, brand, placement site, and hospital unit). Results: Femoral CVL placement was associated with greater risk for developing CLAVT (OR 11.1, 95% CI 3.9-31.6, p<0.0001). CVLs placed in the NICU were also associated with increased CLAVT occurrence (OR 5.3, 95% CI 2.1-13.2, p=0.0003). CVL brand was also significantly associated with risk of CLAVT events. Conclusion: Retrospective analyses identified femoral CVL placement and catheter type as independent risk factors for CLAVT, suggesting increased risks due to mechanical reasons. Placement of CVLs in the NICU also led to an increased risk of CLAVT, suggesting that small infants are at increased risk of thrombotic events. Alternative strategies for CVL placement, thromboprophylaxis, and earlier diagnosis may be important for reducing CLAVT events

Gene expression profiling of childhood adrenocortical tumors.

Pediatric adrenocortical tumors (ACT) are rare and often fatal malignancies; little is known regarding their etiology and biology. To provide additional insight into the nature of ACT, we determined the gene expression profiles of 24 pediatric tumors (five adenomas, 18 carcinomas, and one undetermined) and seven normal adrenal glands. Distinct patterns of gene expression, validated by quantitative real-time PCR and Western blot analysis, were identified that distinguish normal adrenal cortex from tumor. Differences in gene expression were also identified between adrenocortical adenomas and carcinomas. In addition, pediatric adrenocortical carcinomas were found to share similar patterns of gene expression when compared with those published for adult ACT. This study represents the first microarray analysis of childhood ACT. Our findings lay the groundwork for establishing gene expression profiles that may aid in the diagnosis and prognosis of pediatric ACT, and in the identification of signaling pathways that contribute to this disease

Proceedings Of The 23Rd Paediatric Rheumatology European Society Congress: Part Two

PubMe

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licenseBackground: Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide. Methods: A multimethods analysis was performed as part of the GlobalSurg 3 study—a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital. Findings: Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3·85 [95% CI 2·58–5·75]; p<0·0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63·0% vs 82·7%; OR 0·35 [0·23–0·53]; p<0·0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer. Interpretation: Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised. Funding: National Institute for Health and Care Research