Formaldehyde (FA), a major industrial chemical and ubiquitous environmental pollutant, has recently been classified by the International Agency for Research on Cancer as a human leukemogen. The major mode of action of FA is thought to be the formation of DNA-protein crosslinks (DPCs). Repair of DPCs may be mediated by the Fanconi anemia pathway; however, data supporting the involvement of this pathway is limited, particularly in human hematopoietic cells. Therefore, we assessed the role of FANCD2, a critical component of the Fanconi anemia pathway, in FA-induced toxicity in human lymphoblast cell models of FANCD2-deficiency (PD20 cells) and FANCD2-sufficiency (PD20-D2 cells). After treatment of the cells with 0-150 μM FA for 24 hours, DPCs were increased in a dose-dependent manner in both cell lines, with greater increases in FANCD2-deficient PD20 cells. FA also induced cytotoxicity, micronuclei, chromosome aberrations, and apoptosis in a dose-dependent manner in both cell lines, with greater increases in cytotoxicity and apoptosis in PD20 cells. Increased levels of γ-ATR and γ-H2AX in both cell lines suggested the recognition of FA-induced DNA damage; however, the induction of BRCA2 was compromised in FANCD2-deficient PD20 cells, potentially reducing the capacity to repair DPCs. Together, these findings suggest that FANCD2 protein and the Fanconi anemia pathway are essential to protect human lymphoblastoid cells against FA toxicity. Future studies are needed to delineate the role of this pathway in mitigating FA-induced toxicity, particularly in hematopoietic stem cells, the target cells in leukemia.
Here we are reporting a rare phenomenon associated with ventriculoperitoneal (VP) shunt in the adult patient, namely, the development and finding of intraparenchymal pericatheter cerebrospinal fluid cyst. Our patient had a VP shunt placed for idiopathic intracranial hypertension 16 years ago before presentation to the hospital. The patient was admitted to the hospital for headache for past three weeks with the initial CT scan showing encephalomalacia and vasogenic edema. MRI showed the presence of a 4-cm intraparenchymal cyst in the right frontal lobe with surrounding vasogenic edema. The patient underwent two surgeries with the initial surgery for the drainage of cyst and second surgery for the placement of the cystoperitoneal shunt. Catheter-associated cysts are easily misdiagnosed due to their similarity in appearance to abscesses and other malignancies on imaging, and there are no guidelines yet on their evaluation and management. This is a unique case as the pericatheter cyst developed 16 years after the initial VP shunt placed. Given the rarity of this presentation, we hope that our case report can contribute to the development of guidelines and treatment options in adults with long-standing VP shunts.
Objective: The primary objective of this study was to determine if the addition of procalcitonin to the existing systemic inflammatory response syndrome (SIRS) and quick Sepsis-related Organ Failure Assessment (qSOFA) scoring systems could improve the predictability of in-hospital sepsis-related mortality. Secondarily, we sought to determine if the addition of procalcitonin could predict the likelihood of ICU admission and discharge home. Design: This is a retrospective, single-center, observational study that looked at data from January 1, 2017 to January 1, 2019. Patients were stratified into four groups: SIRS-positive + procalcitonin >2 ng/mL (pSIRS+), SIRS-positive + procalcitonin ≤2 ng/mL (pSIRS-), qSOFA-positive + procalcitonin >2 ng/mL (pqSOFA+), and qSOFA-positive + procalcitonin ≤2 ng/mL (pqSOFA-). Setting: The study was conducted at a community hospital in Las Vegas, Nevada. Patients: Patients were included in the study if they were >18 years of age and had hospital admission diagnosis of sepsis with at least one value of procalcitonin level. Interventions: After patients which met the inclusion criteria, patients were divided into subgroups of SIRS, SIRS + procalcitonin > 2 ng/mL, qSOFA, qSOFA + procalcitonin >2 ng/mL. Primary outcomes were in-hospital mortality and secondary outcomes were ICU admission, length of stay, and discharge to home. Results: 933 patients were included in the study with an overall mortality rate of 21.22%, an overall ICU admission rate of 56.15%, and an overall discharge home rate of 29.58%. In those identified with a sepsis-related diagnosis code, pSIRS+ predicted an in-hospital mortality rate of 31.89% compared to pSIRS- 16.15% (P < 0.0001). In regards to qSOFA, the addition of procalcitonin added no statistically significant difference in predicting in-hospital mortality. pSIRS+ patients were found to have an ICU admission rate of 76.16% and a discharge home rate of 19.20% compared to pSIRS- who had 47.40% and 34.90%, respectively (P < 0.0001). Like in our primary outcome, our data for qSOFA was not statistically significant. Conclusions: Procalcitonin added utility to the SIRS scoring system in predicting sepsis-related in-hospital mortality, ICU admission, and discharge home. Procalcitonin did not add statistically significant benefit to the qSOFA scoring system in predicting sepsis-related in-hospital mortality, ICU admission, and discharge home.
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