Prognostic Significance of NRAS Gene Mutations in Children with Acute Myelogenous Leukemia

Background: NRAS mutations are the most commonly detected molecular abnormalities  in hematologic malignancies, especially in those of myeloid origin. Objective: We aimed to determine the frequency of NRAS (NRAS ) mutation; and its prognostic significance in Egyptian children with acute myelogenous leukemia (AML). Subject and methods: Peripheral blood and bone marrow (BM) samples were taken from  39 de novo pediatric AML patients. Twenty subjects with matched age and sex were  selected as a control group. Samples from patients and control were analyzed for Exons 1, 2 of NRAS gene using genomic PCR-SSCP method. Results: NRAS mutations at the time of diagnosis was found in 6/39 (15.4%) AML  cases.  Patients with NRAS   had no significant  improved clinical  outcome than patients without mutation. Patients with NRAS  had similar complete remission (CR) rates compared with non mutated patients (66.7% vs. 69.5%, P=0.43).  Those in CR had a similar relapse rate regardless of the presence ofNRAS  (RR 33.4% vs. 30.2%, P=0.26).  However, an adverse prognosis for 3 year overall survival (OS) was associated with the presence of NRAS mutations. This adverse prognosis associated with NRAS mutations was also observed in terms  of disease-free survival (DFS)  (P=0.007). Univariate analysis showed that unfavorable prognostic factors for DFS were cytogenetic data (P = 0.005) and the NRAS gene mutation (P = 0.002).  Conclusion: NRAS  did not contribute to increase the disease recurrence, however NRAS  was found to be a poor prognostic factor for children with AML. Further studies to confirm these findings are required because of the small number of patients with NRAS mutation

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.The aim of this study was to inform vaccination prioritization by modelling the impact of vaccination on elective inpatient surgery. The study found that patients aged at least 70 years needing elective surgery should be prioritized alongside other high-risk groups during early vaccination programmes. Once vaccines are rolled out to younger populations, prioritizing surgical patients is advantageous