Impaired DNA Double-Strand Break Repair in Irradiated Sheep Lung Fibroblasts: Late Effects of Previous Irradiation of the Spinal Thecal Sac.

Children with cancer previously treated with radiotherapy face the likelihood of side effects that can be debilitating or fatal. This study aimed to assess the long-term effect of medulloblastoma radiotherapy on the DNA double-strand break (DSB) repair capability of primary fibroblasts derived from lung biopsies of previously irradiated young sheep. This study included biopsies from three control and five irradiated sheep. The treated sheep had previously received spinal radiotherapy at a total dose of 28 Gy, which is equivalent to pediatric medulloblastoma treatment. Lung biopsies were taken 4 years post-irradiation from high-dose (HD, >18 Gy) and low-dose (LD, <2 Gy) regions. Fifteen cell lines were extracted (six control, four LD and five HD). The cells were irradiated, and DNA DSB repair was analyzed by immunofluorescence. Clonogenic, trypan blue and micronuclei assays were performed. Both the HD and LD cell lines had a significantly higher number of residual γH2AX foci 24 h and a significant decrease in pATM activity post-irradiation compared to the control. There was no statistically significant difference in the clonogenic assay, trypan blue and micronuclei results. Our study showed that a previous irradiation can impair the DNA DSB repair mechanism of ovine lung fibroblasts.

Evaluating The Role of ChatGPT as a Study Aid in Medical Education in Surgery.

OBJECTIVE: Our aim was to assess how ChatGPT compares to Google search in assisting medical students during their surgery clerkships. DESIGN: We conducted a crossover study where participants were asked to complete 2 standardized assessments on different general surgery topics before and after they used either Google search or ChatGPT. SETTING: The study was conducted at the Perelman School of Medicine at the University of Pennsylvania (PSOM) in Philadelphia, Pennsylvania. PARTICIPANTS: 19 third-year medical students participated in our study. RESULTS: The baseline (preintervention) performance of participants on both quizzes did not differ between the Google search and ChatGPT groups (p = 0.728). Students overall performed better postintervention and the difference in test scores was statistically significant for both the Google group (p < 0.001) and the ChatGPT group (p = 0.01). The mean percent increase in test scores pre- and postintervention was higher in the Google group at 11% vs. 10% in the ChatGPT group, but this difference was not statistically significant (p = 0.87). Similarly, there was no statistically significant difference in postintervention scores on both assessments between the 2 groups (p = 0.508). Postassessment surveys revealed that all students (100%) have known about ChatGPT before, and 47% have previously used it for various purposes. On a scale of 1 to 10 with 1 being the lowest and 10 being the highest, the feasibility of ChatGPT and its usefulness in finding answers were rated as 8.4 and 6.6 on average, respectively. When asked to rate the likelihood of using ChatGPT in their surgery rotation, the answers ranged between 1 and 3 ("Unlikely" 47%), 4 to 6 ("intermediate" 26%), and 7 to 10 ("likely" 26%). CONCLUSION: Our results show that even though ChatGPT was comparable to Google search in finding answers pertaining to surgery questions, many students were reluctant to use ChatGPT for learning purposes during their surgery clerkship.

Impact of COVID-19 Pandemic Surge on Surgical Outcomes: A Retrospective Study.

BACKGROUND: The COVID-19 pandemic posed significant challenges to healthcare systems worldwide, including surgical care. While many studies examined the effect of the pandemic on different patient outcomes, there are none to date examining the impact of the pandemic surge on surgical outcomes. Our aim is to evaluate the impact of the COVID-19 surges on surgical outcomes using data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. METHODS: A single-center retrospective analysis of 7436 patients who underwent surgery between February 2020 and December 2022 was conducted. Patients were divided into those who underwent surgery during the surge of the pandemic (n = 1217) or outside that period (n = 6219). Primary outcomes were 30-day mortality and morbidity. Secondary outcomes included 30-day mortality, operation time, transfusion, reoperation, and specific postoperative complications. Multivariable logistic regression was used in our analysis. All analyses were conducted using the software "R" version 4.2.1. Statistical significance was set at α = .05 level. RESULTS: After adjusting for confounders, we found no significant difference in 30-day mortality and morbidity (OR: 1.06, 95% CI: .89-1.226, P = .5173) or 30-day mortality only (OR: 1.39, 95% CI: .788-2.14, P = .1364) between the two groups. No significant differences were observed in secondary outcomes. Sensitivity analyses yielded similar results to the multivariable logistic regression. CONCLUSION: We found no evidence of increased 30-day mortality and morbidity in patients undergoing surgery during the COVID-19 surges compared to those undergoing surgery outside that period. Our results suggest that surgical care was maintained despite the challenges of the pandemic surges.

A Narrative Review on Intraoperative Adverse Events: Risks, Prevention, and Mitigation.

INTRODUCTION: Adverse events from surgical interventions are common. They can occur at various stages of surgical care, and they carry a heavy burden on the different parties involved. While extensive research and efforts have been made to better understand the etiologies of postoperative complications, more research on intraoperative adverse events (iAEs) remains to be done. METHODS: In this article, we reviewed the literature looking at iAEs to discuss their risk factors, their implications on surgical care, and the current efforts to mitigate and manage them. RESULTS: Risk factors for iAEs are diverse and are dictated by patient-related risk factors, the nature and complexity of the procedures, the surgeon's experience, and the work environment of the operating room. The implications of iAEs vary according to their severity and include increased rates of 30-day postoperative morbidity and mortality, increased length of hospital stay and readmission, increased care cost, and a second victim emotional toll on the operating surgeon. CONCLUSIONS: While transparent reporting of iAEs remains a challenge, many efforts are using new measures not only to report iAEs but also to provide better surveillance, prevention, and mitigation strategies to reduce their overall adverse impact.

Risk of thromboembolic events in non-hospitalized COVID-19 patients: A systematic review.

The risk of thromboembolism in non-hospitalized COVID-19 patients remains uncertain and was assessed in this review to better weigh benefits vs. risks of prophylactic anticoagulation in this population. A search was performed through three databases: Medline, Embase, and Cochrane Library until 2022. Self-controlled case series, case-control and cohort studies were included, and findings summarized narratively. Meta-analyses for risk of thromboembolism including deep vein thrombosis (DVT), pulmonary embolism (PE), and myocardial infarction (MI) between COVID-19 and non-COVID-19 non-hospitalized patients were conducted. Frequency, incidence rate ratio (IRR), and risk ratio (RR) of stroke were used to assess risk in non-hospitalized COVID-19 patients considering the lack of studies to conduct a meta-analysis. Ten studies met inclusion criteria characterized by adult non-hospitalized COVID-19 patients. Risk of bias was relatively low. Risk of DVT (RR: 1.98 with 95% CI: 1.03-3.83) and PE (OR: 6.72 with 95% CI: 4.81-9.39 and RR: 4.44 with 95% CI: 1.98-9.99) increased in non-hospitalized COVID-19 patients compared to controls. Risk of MI (OR: 1.91 with 95% CI: 0.89-4.09) is possibly increased in non-hospitalized COVID-19 patients with moderate certainty when compared to controls. A trend in favor of stroke was documented in the first week following infection. Our meta-analyses support the increase in risk of DVT and PE, and likely increase of MI, in non-hospitalized COVID-19 patients. The risk of stroke appears significant in the first week following infection but drops to insignificance two weeks later. More studies are needed to establish evidence-based recommendations for prophylactic anticoagulation therapy in non-hospitalized COVID-19 patients.

Recognizing who is at risk for postpartum hemorrhage: targeting anemic women and scoring systems for clinical use.

Iron deficiency anemia during pregnancy is a common concern, affecting 38% of women worldwide and up to 50% in developing countries. It is defined differently throughout all 3 trimesters. It has several detrimental effects on pregnancy outcomes for both the mother and the fetus, such as increasing the risk for postpartum depression, preterm delivery, cesarean delivery, preeclampsia, and low birthweight. Management of iron deficiency anemia is done classically via oral iron supplementation. However, recent evidence has shown that intravenous iron is a good alternative to oral iron if patients are unable to tolerate it, not responding, or present with a new diagnosis very late in pregnancy. Management of iron deficiency anemia was demonstrated to be protective against postpartum hemorrhage. Other ways to prevent postpartum hemorrhage include improving prediction tools that can identify those at risk. Several risk assessment kits have been developed to estimate the risk for postpartum hemorrhage among patients and have been proven useful in the prediction of patients at high risk for postpartum hemorrhage despite limitations among low-risk groups. More comprehensive tools are also being explored by determining clinically relevant factors through nomograms, with some proving their efficacy after implementation. Machine learning is also being used to develop more complete tools by including risk factors previously not accounted for. These newer tools, however, still require external validation before being adopted despite promising results under testing conditions.

Knowledge, Attitude, and Beliefs of Medication Use in Pregnancy in an Urban Tertiary Care Center.

Medication use in pregnancy is common. However, there is a gap in the literature assessing the knowledge of pregnant individuals about medication use in pregnancy. The aim of our study is to assess the knowledge, attitudes, and beliefs of pregnant people on medication use in pregnancy. We conducted a cross-sectional survey questionnaire that was completed by pregnant patients from December 2021 to January 2022. The survey included questions regarding knowledge, attitude, and sources for obtaining information about medication use in pregnancy and general statements from the Beliefs about Medicines Questionnaire (BMQ). A total of 150 participants completed the survey. Most patients reported that a person should know that medication use for chronic diseases must be modified during pregnancy and that medications can be used in any trimester of pregnancy. Most reported that medication use can lead to fetal growth restriction and maternal bleeding. The mean scores (SDs) on the BMQ-General for the overuse, harm, and benefit statements were 8.7 (2.4), 8.2 (3.1), and 15.7 (2.8). Even though medication use in pregnancy is common, it is an area of concern to pregnant patients. More research on identifying the risks of different medicines used in pregnancy is thus needed.

Preoperative MELD score predicts adverse outcomes following gastrectomy: An ACS NSQIP analysis.

BACKGROUND: The Model End-Stage Liver Disease (MELD) has been widely used to predict the mortality and morbidity of various surgical procedures. We aimed to assess the impact of preoperative MELD score on adverse 30-day postoperative outcomes following gastrectomy. METHODS: Patients who underwent elective, non-emergent gastrectomy were identified from the ACS NSQIP 2014-2019 database. Patients were categorized according to a calculated MELD score. The primary outcomes of this study were the 30-day overall complications and major complication rates following gastrectomy. RESULTS: Compared to MELD <11, patients with MELD ≥11 had significantly higher rates of mortality, any complication, and major complication. MELD score ≥11 was significantly associated with any complication (OR 1.73, p = 0.011) and major complications (1.85, p = 0.014) on multivariate analysis. CONCLUSIONS: MELD score ≥11 was associated with poorer outcomes in patients undergoing gastrectomy compared to lower MELD scores.

Tideglusib attenuates growth of neuroblastoma cancer stem/progenitor cells in vitro and in vivo by specifically targeting GSK-3ß.

BACKGROUND: Neuroblastoma (NB) is the most frequently diagnosed extracranial solid tumor among the pediatric population. It is an embryonic tumor with high relapse rates pertaining to the presence of dormant slowly dividing cancer stem cells (CSC) within the tumor bulk that are responsible for therapy resistance. Therefore, there is a dire need to develop new therapeutic approaches that specifically target NB CSCs. Glycogen synthase kinase (GSK)-3ß is a serine/threonine kinase that represents a common signaling node at the intersection of many pathways implicated in NB CSCs. GSK-3ß sustains the survival and maintenance of CSCs and renders them insensitive to chemotherapeutic agents and radiation. METHODS: In our study, we aimed at evaluating the potential anti-tumor effect of Tideglusib (TDG), an irreversible GSK-3ß inhibitor drug, on three human NB cell lines, SK-N-SH, SH-SY5Y, and IMR-32. RESULTS: Our results showed that TDG significantly reduced cell proliferation, viability, and migration of the NB cells, in a dose- and time-dependent manner, and also significantly hindered the neurospheres formation eradicating the self-renewal ability of highly resistant CSCs. Besides, TDG potently reduced CD133 cancer stem cell marker expression in both SH-SY5Y cells and G1 spheres. Lastly, TDG inhibited NB tumor growth and progression in vivo. CONCLUSION: Collectively, we concluded that TDG could serve as an effective treatment capable of targeting the NB CSCs and hence overcoming therapy resistance. Yet, future studies are warranted to further investigate its potential role in NB and decipher the subcellular and molecular mechanisms underlying this role.

The potential use of tideglusib as an adjuvant radio-therapeutic treatment for glioblastoma multiforme cancer stem-like cells.

BACKGROUND: Glioblastoma multiforme (GBM), a stage IV astrocytoma, is the most common brain malignancy among adults. Conventional treatments of surgical resection followed by radio and/or chemotherapy fail to completely eradicate the tumor. Resistance to the currently available therapies is mainly attributed to a subpopulation of cancer stem cells (CSCs) present within the tumor bulk that self-renew leading to tumor relapse with time. Therefore, identification of characteristic markers specific to these cells is crucial for the development of targeted therapies. Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase, is deregulated in a wide range of diseases, including cancer. In GBM, GSK-3ß is overexpressed and its suppression in vitro has been shown to induce apoptosis of cancer cells. METHODS: In our study, we assessed the effect of GSK-3ß inhibition with Tideglusib (TDG), an irreversible non-ATP competitive inhibitor, using two human GBM cell lines, U-251 MG and U-118 MG. In addition, we combined TDG with radiotherapy to assess whether this inhibition enhances the effect of standard treatment. RESULTS: Our results showed that TDG significantly reduced cell proliferation, cell viability, and migration of both GBM cell lines in a dose- and time-dependent manner in vitro. Treatment with TDG alone and in combination with radiation significantly decreased the colony formation of U-251 MG cells and the sphere formation of both cell lines, by targeting and reducing their glioblastoma cancer stem-like cells (GSCs) population. Finally, cells treated with TDG showed an increased level of unrepaired radio-induced DNA damage and, thus, became sensitized toward radiation. CONCLUSIONS: In conclusion, TDG has proven its effectiveness in targeting the cancerous properties of GBM in vitro and may, hence, serve as a potential adjuvant radio-therapeutic agent to better target this deadly tumor.