ABSTRACT
Introduction Biliary diseases are a major acute general surgical burden. Laparoscopic cholecystectomy is the gold standard surgical procedure, although it was discontinued during an outbreak. Effective management permits decisive therapy, symptom alleviation, and fewer hospitalizations and complications. Throughout the initial COVID-19 situation, surgical procedures for patients were delayed. Invasive services were required to employ conservative or non-operative therapy, which could lead to increased recurring presentations and biliary-pancreatic problems. Aim Examining the impact of COVID-19 on the outcomes and hospitalizations of patients suffering from gallstone, biliary tract, and pancreatic diseases. Methods The retrospective analysis included patients with the following ICD-10 codes who presented to our unit: cholelithiasis (K80), cholecystitis (K81), and acute pancreatitis (K85). We compared the interval of the first COVID-19 pandemic wave, from March to August 2020, with the period before the pandemic, referred to as Pre-COVID-19. After applying exclusion criteria, a total of 868 patients were enrolled in the trial, having initially recruited around 1,400 individuals using these codes. Patients with inaccurate coding, cancer, or non-stone disease were excluded (e.g., alcoholic pancreatitis). The demographic information, admission details, investigations, surgical therapy, operating specifics, and postoperative complications of the patients were noted. Changes in surgical management, patient representation, and postoperative complications were the key outcomes. Results A statistically significant (p<0.05) rise was seen in repeat presentations in the COVID group, most likely due to the failure of definitive treatment. The other outcome is the distribution of presentations was comparable, patients with acute cholecystitis and gallstone pancreatitis showed statistically significant (p<0.05) lower rates of definitive therapy. Conclusion During the COVID period, all surgeries except those for cancer were halted. Unknown causes led to several consequences related to the gallbladder, biliary tract, and pancreas. Patients with cholecystitis, gallstone pancreatitis, and pancreatic inflammation experienced a lower probability of treatment. The increase in hospitalizations and self-presentations indicated that definitive therapy, designed to restrict COVID-19 exposure, actually increased patient risk. Despite this risk, we had no COVID-19 instances in our cohort. The evaluation of the long-term consequences of the pandemic on acute pancreatitis and its care will require a large-scale, multicenter investigation.
ABSTRACT
FOXO1 has an oncogenic role in adult germinal center-derived lymphomas, in which mutations, predominately within the AKT recognition motif, cause nuclear retention of FOXO1, resulting in increased cell proliferation. To determine the prevalence and distribution of FOXO1 mutations in pediatric Burkitt lymphoma (BL), we sequenced a large number of sporadic and endemic BL patient samples. We report a high frequency of FOXO1 mutations in both sporadic and endemic BL at diagnosis, occurring in 23/78 (29%) and 48/89 (54%) samples, respectively, as well as 8/16 (50%) cases at relapse. Mutations of T24 were the most common in sporadic BL but were rare in endemic cases, in which mutations of residue S22, also within the AKT recognition motif, were the most frequent. FOXO1 mutations were almost always present in the major tumor cell clone but were not associated with outcome. Analysis of other recurrent mutations reported in BL revealed that FOXO1 mutations were associated with mutations of DDX3X and ARID1A, but not MYC, TCF3/ID3, or members of the phosphatidylinositol 3-kinase signaling pathway. We further show common nuclear retention of the FOXO1 protein, irrespective of mutation status, suggesting alternative unknown mechanisms for maintaining FOXO1 transcriptional activity in BL. CRISPR/Cas9 knockout of FOXO1 in an endemic cell line produced a significant decrease in cell proliferation, supporting an oncogenic role for FOXO1 in endemic BL. Thus, FOXO1 is frequently mutated in both sporadic and endemic BL and may offer a potential therapeutic target for pediatric BL patients worldwide.
