Knowledge, awareness and attitude towards breast cancer: Risk factors, signs and screening among Health and Allied students: A prospective study.

Introduction: Breast cancer (BC) is the second most common cancer in Saudi women. Therefore, understanding BC and its related risk factors, symptoms, and screening is critical for early detection and intervention. The current study was meant to explore the knowledge, awareness, and attitude (KAA) gap in BC: risk factors, symptoms, and screening. Material and Methods: This cross-sectional investigation was carried out with Health Professions Students (HPS) using a predesigned and validated study questionnaire to examine HPS knowledge and attitudes concerning BC and associated risk factors, symptoms, and screening. Results: A total of 277 female students responded to the survey. The frequency of correct answers for the BC knowledge questions varied from the lowest of 27.8% to the highest of 88.8%, with only 5 out of 15 questions (33.3%) answered correctly by more than 60% of the participants, displaying poor knowledge and awareness of BC. A majority (>60%) of the participants identified only 7 of the 18 risk factors of BC correctly, whereas 11 of the 13 early warning signs of BC were identified correctly by the majority (>60%) of the participants. Among the participants, only 26.4% were aware of the breast cancer screening center, but 94.6% of them agreed that early detection of breast cancer is important and 82.7% agreed to participate in the screening program if offered. Conclusion: Participants' knowledge and awareness of BC were found to be relatively low; however, their attitudes towards BC screening were positive. As a result, it is critical to develop effective education programs, curricular activities, and awareness campaigns to address the lack of awareness of BC and to have an appropriate response to screening to reduce disease burden.

A phase ib clinical trial of oral ciprofloxacin and etoposide in subjects with resistant acute myeloid leukemia.

A phase 1b study was conducted to evaluate the safety and feasibility of ciprofloxacin and etoposide combination treatment in subjects with relapsed and refractory acute myeloid leukemia. Eleven subjects were enrolled in the study. Utilizing the standard '3 + 3' design, escalating ciprofloxacin doses (750 mg, 1000 mg) twice daily on D1-D10 in combination with a fixed dose (200 mg) of etoposide on D2-D8 were administered. Maximum tolerated dose was determined to be 1000 mg of ciprofloxacin in combination with 200 mg of etoposide. Serious adverse events occurred in 54.5% (n = 6) subjects and 91% (n = 10) subjects reported ≥ grade 3 toxicities. Nine subjects completed treatment, one had a dose-limiting toxicity, and one withdrew. One subject achieved complete remission with a duration of 111 days and one subject achieved morphologic leukemia-free state after cycle 1. While the combination demonstrated safety and an acceptable toxicity profile, only modest hematologic and clinical benefits were observed.This trial was registered at www.clinicaltrials.gov as #NCT02773732.

EAES/SAGES evidence-based recommendations and expert consensus on optimization of perioperative care in older adults.

BACKGROUND: As the population ages, more older adults are presenting for surgery. Age-related declines in physiological reserve and functional capacity can result in frailty and poor outcomes after surgery. Hence, optimizing perioperative care in older patients is imperative. Enhanced Recovery After Surgery (ERAS) pathways and Minimally Invasive Surgery (MIS) may influence surgical outcomes, but current use and impact on older adults patients is unknown. The aim of this study was to provide evidence-based recommendations on perioperative care of older adults undergoing major abdominal surgery. METHODS: Expert consensus determined working definitions for key terms and metrics related to perioperative care. A systematic literature review and meta-analysis was performed using the PubMed, Embase, Cochrane Library, and Clinicaltrials.gov databases for 24 pre-defined key questions in the topic areas of prehabilitation, MIS, and ERAS in major abdominal surgery (colorectal, upper gastrointestinal (UGI), Hernia, and hepatopancreatic biliary (HPB)) to generate evidence-based recommendations following the GRADE methodology. RESULT: Older adults were defined as 65 years and older. Over 20,000 articles were initially retrieved from search parameters. Evidence synthesis was performed across the three topic areas from 172 studies, with meta-analyses conducted for MIS and ERAS topics. The use of MIS and ERAS was recommended for older adult patients particularly when undergoing colorectal surgery. Expert opinion recommended prehabilitation, cessation of smoking and alcohol, and correction of anemia in all colorectal, UGI, Hernia, and HPB procedures in older adults. All recommendations were conditional, with low to very low certainty of evidence, with the exception of ERAS program in colorectal surgery. CONCLUSIONS: MIS and ERAS are recommended in older adults undergoing major abdominal surgery, with evidence supporting use in colorectal surgery. Though expert opinion supported prehabilitation, there is insufficient evidence supporting use. This work has identified evidence gaps for further studies to optimize older adults undergoing major abdominal surgery.

Global research productivity of post-transplant lymphoproliferative disorder: a bibliometric study.

Background: Post-transplant lymphoproliferative diseases (PTLD) are a heterogeneous collection of neoplasms that occur after solid organ transplants (SOT). In the past 20 years, there has been a rise in PTLD research. This study aims to investigate the global research output and interest regarding PTLD using a bibliometric approach. Material and methods: On 28 November 2022, the Web of Science Core Collection documents on PTLD published between 2000 and 2022 were collected and analyzed using bibliometric techniques. The VOSviewer application was utilized to visualize the annual number of publications, authors, organizations, countries, published journals, citations, and most occurring keywords. Results: A total of 2814 documents were retrieved, and a screening process included 1809 documents. The total number of citations was 45 239, and the average number per item was 25. Most articles (n = 747) and citations (n = 25 740) were produced in the United States. Based on citations, most of the top 10 institutions that contributed were in the United States of America. The University of Pittsburgh topped the list with 2700 citations and 64 articles. The vast majority of articles were published in Pediatric Transplantation (n = 147), Transplantation (n = 124), and the American Journal of Transplantation (n = 98). Transplantation has received the most citations, 6499, followed by the American Journal of Transplantation with 5958 citations and Blood with 4107 citations. Conclusion: With ongoing debates over optimal classification, Epstein-Bar virus involvement, and treatment, this topic has received significant interest from researchers in recent years. Our results can be used as a guide for future research in the field and as a framework for a more in-depth look at the scientific progress of PTLD.

The association of hernia-specific and procedural risk factors with early complications in ventral hernia repair: ACHQC analysis.

BACKGROUND: Many surgical risk assessment tools emphasize patient-specific risk factors. Our objective was to use a hernia-specific database to assess risk factors of complications in ventral hernia repair (VHR) focusing on hernia-specific and procedural factors. METHODS: The ACHQC database was queried for elective VHR in adults from 2012 to 2023. Primary outcome was overall 30-day complications. Multivariable logistic regression was used for analysis. RESULTS: 41,526 VHR were included. The rate of 30-day complications was 18%, surgical site infection 3%, surgical site occurrence requiring procedural intervention 4%, readmission 4%, reoperation 2%, and mortality 0.2%. Multivariable analysis demonstrated that BMI, ASA, frailty, COPD, anticoagulants, defect width, incisional and recurrent hernias, presence of stoma or prior mesh, prior abdominal wall infection, non-clean wound, operative time, open approach and myofascial release were associated with 30-day complications (OR â€‹= â€‹1.01-1.66). Preoperative chlorhexidine, bowel preparation and fascial closure were associated with lower complication risk (OR â€‹= â€‹0.70-0.89). CONCLUSION: Hernia and procedural risk factors are associated with early complications following elective VHR. These factors need to be included in surgical risk assessment tools, to supplement patient-specific factors.

Structure-Based In Silico Approaches Reveal IRESSA as a Multitargeted Breast Cancer Regulatory, Signalling, and Receptor Protein Inhibitor.

Breast cancer begins in the breast cells, mainly impacting women. It starts in the cells that line the milk ducts or lobules responsible for producing milk and can spread to nearby tissues and other body parts. In 2020, around 2.3 million women across the globe received a diagnosis, with an estimated 685,000 deaths. Additionally, 7.8 million women were living with breast cancer, making it the fifth leading cause of cancer-related deaths among women. The mutational changes, overexpression of drug efflux pumps, activation of alternative signalling pathways, tumour microenvironment, and cancer stem cells are causing higher levels of drug resistance, and one of the major solutions is to identify multitargeted drugs. In our research, we conducted a comprehensive screening using HTVS, SP, and XP, followed by an MM/GBSA computation of human-approved drugs targeting HER2/neu, BRCA1, PIK3CA, and ESR1. Our analysis pinpointed IRESSA (Gefitinib-DB00317) as a multitargeted inhibitor for these proteins, revealing docking scores ranging from -4.527 to -8.809 Kcal/mol and MM/GBSA scores between -49.09 and -61.74 Kcal/mol. We selected interacting residues as fingerprints, pinpointing 8LEU, 6VAL, 6LYS, 6ASN, 5ILE, and 5GLU as the most prevalent in interactions. Subsequently, we analysed the ADMET properties and compared them with the standard values of QikProp. We extended our study for DFT computations with Jaguar and plotted the electrostatic potential, HOMO and LUMO regions, and electron density, followed by a molecular dynamics simulation for 100 ns in water, showing an utterly stable performance, making it a suitable drug candidate. IRESSA is FDA-approved for lung cancer, which shares some pathways with breast cancers, clearing the hurdles of multitargeted drugs against breast and lung cancer. This has the potential to be groundbreaking; however, more studies are needed to concreate IRESSA's role.

Motivators for the public to receive the seasonal influenza vaccination and the effect of coronavirus disease 2019 pandemic on the uptake of the seasonal influenza vaccination.

BACKGROUND: The coverage of the seasonal influenza vaccine has always been sub-par. Understanding the motivators of receiving vaccines, especially during pandemics, could enhance and increase the coverage rates. The Saudi Ministry of Health launched its annual influenza vaccination campaign during the 2021 influenza season and provided vaccinations in primary healthcare settings. This study aims to explore public motivators to receive influenza vaccination, particularly during the coronavirus disease 2019 global pandemic. MATERIALS AND METHODS: This cross-sectional study enrolled 783 participants who attended the influenza vaccination campaign. All persons who received the influenza vaccine in the influenza vaccination campaign held in Dammam, Saudi Arabia, from October to November 2021, were interviewed and completed a self-administered questionnaire. Odds ratio with a 95% confidence interval were estimated using the full model fit. The significance level was set as α = 0.05. RESULTS: The majority of the participants had more than high school education (81%), were males (66.2%), and married (59.6%), and 50.6% were below 35 years of age. Participants with higher education, health-care workers, and those who had been previously counseled on influenza vaccination were less likely to have started taking the influenza vaccination, whereas smokers and persons who do not have routine checkups were more likely to start influenza vaccination. The main motivator to take the influenza vaccine was the establishment of a vaccination campaign near the participant's workplace (62.2%), followed by advice from their physician (30.3%), and fear of having influenza disease (29.6%). CONCLUSION: Accessibility to the vaccination campaigns was the main motivator for receiving the vaccine followed by the advice from physician. Advice from physician and increasing mobile vaccination campaigns and mobile clinics would substantially increase influenza vaccine uptake.

Forecasting The Impact of the 2023 Current Procedural Terminology Coding Changes On Ventral Hernia Work Relative Value Units. A Cross-Sectional Study.

BACKGROUND: In January 2023, significant changes were implemented to ventral hernia repair Current Procedural Terminology codes, with new codes replacing previous codes. The new codes were assigned a 0-day global period. The impact of these changes on clinical productivity remains unclear. Our objective was to forecast the impact of Current Procedural Terminology changes on ventral hernia-related work relative value units using historical data. METHODS: Ventral hernia repairs performed between March 2021 and December 2022 on adults by a single surgeon with available 90-day follow-up were retrospectively retrieved from the Abdominal Core Health Quality Collaborative. Demographic, hernia, and operative and postoperative data were collected. The ventral hernia repairs were coded twice using the previous and new Current Procedural Terminology codes, and work relative value units were calculated using both systems. The median work relative value units per case were compared using the Wilcoxon signed-rank test. RESULTS: A total of 143 ventral hernia repairs were included. The median age was 59 years, and 50% of patients were male. Median hernia width and length were 3.5 and 5.0 cm, respectively. The most common ventral hernia types were incisional 57% and umbilical 33%. Twenty percent of hernias were recurrent, and 99% were elective repairs. 49% of the procedures were open, 30% robotic, and 21% laparoscopic. Component separation was performed in 16%. The median length of stay was 0.0, and the median number of 90-day outpatient postoperative visits was 1.0. The new Current Procedural Terminology coding system was associated with a higher median 90-day work relative value units per case (14.1) than the previous system (13.8) (P = .002). Subset analysis identified statistically higher median 90-day work relative value units per case using the new versus previous Current Procedural Terminology codes for hernias with the largest defect dimension >10 cm (23.3 vs 18.8), umbilical/epigastric/Spigelian hernias (9.2 vs 7.1), recurrent hernias (20.1 vs 17.3) and open ventral hernia repairs (9.8 vs 7.1), all P < .05. Median 90-day work relative value units per case were statistically lower using the new versus previous codes for non-recurrent (11.6 vs 13.8) and incarcerated/strangulated (14.8 vs 14.9) hernias, all P < .05. In the new coding system, postoperative care within 90-days contributed to a median of 1.3 work relative value units per case (9% of total 90-day work relative value units). CONCLUSION: We forecast that in our practice, the 2023 ventral hernia repair Current Procedural Terminology changes will result in a modest impact on clinical productivity. The impact of these changes on a particular practice depends on surgical practice patterns and ventral hernia case mix.

Delineating Pixantrone Maleate's adroit activity against cervical cancer proteins through multitargeted docking-based MM\GBSA, QM-DFT and MD simulation.

Cervical cancer poses a substantial worldwide health challenge, especially in low- and middle-income nations, caused by high-risk types of human papillomavirus. It accounted for a significant percentage of cancer-related deaths among women, particularly in areas with limited healthcare resources, necessitating innovative therapeutic approaches, and single-targeted studies have produced significant results, with a considerable chance of developing resistance. Therefore, the multitargeted studies can work as a beacon of hope. This study is focused on performing the multitargeted molecular docking of FDA-approved drugs with the three crucial proteins TBK1, DNA polymerase epsilon, and integrin α-V ß-8 of cervical cancer. The docking studies using multisampling algorithms HTVS, SP, and XP reveal Pixantrone Maleate (DB06193) as a multitargeted inhibitor with docking scores of -8.147, -8.206 and -7.31 Kcal/mol and pose filtration with MM\GBSA computations with scores -40.55, -33.67, and -37.64 Kcal/mol. We also have performed QM-based DFT and pharmacokinetics studies of the compound and compared it with the standard values, which results in the compound being entirely suitable against cervical cancer proteins. The interaction fingerprints have revealed that PHE, VAL, SER and ALA are the residues among most interactions. We also explore the stability of the multitargeted potential of Pixantrone Maleate through 100ns MD simulations and investigate the RMSD, RMSF and intermolecular interactions between all three proteins-ligand complexes. All computational studies favour Pixantrone Maleate as a multitargeted inhibitor of the TBK1, DNA polymerase epsilon, and integrin α-V ß-8 and can be validated experimentally before use.

Physical accessibility, availability, financial affordability, and acceptability of mobile health clinics in remote areas of Saudi Arabia.

Introduction: Access to primary healthcare (PHC) services is a significant concern, especially for those living in remote areas. Mobile health clinics (MHCs) are a model widely used to enhance access to healthcare in rural areas. In Saudi Arabia, the Ministry of Health has launched mobile clinics to facilitate access to PHC and increase access to healthcare. This study aims to assess the accessibility of MHCs in rural areas of Saudi Arabia measuring four dimensions of access from the patient's perspective: physical accessibility, availability, financial affordability, and acceptability. Methods: A quantitative cross-sectional survey in the form of an interviewer-administered questionnaire was performed on patients who attended mobile clinics between August and October 2020. All these people have been targeted to be interviewed as a nonprobability sample. Data was collected through a survey filled out by the interviewer. Results: Five hundred participants were interviewed in nine mobile clinics in the nine cities of the Kingdom. The majority were men (82.4%) and from Makkah city (13.6%) and 94.2% of the participants were Saudi nationals. In total, 98.3% of the respondents were satisfied with the overall mobile clinic services and 11.4% of the participants had difficulties with the mobile clinics' work schedules. There was a positive correlation between access to mobile clinics and satisfaction. Conclusions: The mobile clinics in rural and remote areas in Saudi Arabia during the study period were accessible to the respondents and met patient satisfaction. Most participants accept the work schedule for mobile clinics. However, it requires further improvements to meet all access dimensions of the study.

Hepatic ultrastructural alterations induced by copper oxide nanoparticles: In vivo electron microscopy study.

Copper oxide nanomaterials (CuO NPs) have been widely utilized in many fields, including antibacterial materials, anti-tumor, osteoporosis treatments, imaging, drug delivery, cosmetics, lubricants for metallic coating, the food industry, and electronics. Little is known about the potential risk to human health and ecosystems. The present work was conducted to investigate the ultrastructural changes induced by 20 ± 5 nm CuO NPs in hepatic tissues. Adult healthy male Wister albino rats were exposed to 36 intraperitoneal (ip) injections of 25 nm CuO NPs (2 mg/kg bw). Liver biopsies from all rats under study were processed for transmission electron microscopy (TEM) processing and examination for hepatic ultrastructural alterations. The hepatic tissue of rats exposed to repeated administrations of CuO NPs exhibited the following ultrastructural alterations: extensive mitochondrial damage in the form of swelling, crystolysis and matrix lysis, formation of phagocytized bodies and myelin multilayer figures, lysosomal hyperplasia, cytoplasmic degeneration and vacuolation, fat globules precipitation, chromatin clumping, and nuclear envelope irregularity. The findings indicated that CuO NPs interact with the hepatic tissue components and could induce alterations in the hepatocytes with the mitochondria as the main target organelles of copper nanomaterials. More work is recommended for better understanding the pathogenesis of CuO NPs.

Gender, racial, and socioeconomic disparity of preoperative optimization goals in ventral hernia repair.

BACKGROUND: Preoperative optimization cut-offs are frequently utilized to determine eligibility for elective ventral hernia repair. Our objective was to assess the relationship between gender, race, and socioeconomic status and preoperative optimization goals. METHODS: We queried our institutional database for adults with ventral hernia diagnoses between 2016 and 2021. Demographics, comorbidities, laboratory, and operative data were collected and analyzed. The following cut-offs were used to determine eligibility for elective repair: body mass index (BMI) < 40 kg/m2, no active smoking, and glycated hemoglobin (HbA1c) < 8%. Socioeconomic status was assessed using the Distressed Communities Index. RESULTS: A total of 5638 patients were included [Whites = 4321 (77%), Blacks = 794 (14%), Hispanics = 318 (6%), and other/unknown 205 (4%)]. Median age was 61 years and 50% were male. Most common hernia types were umbilical (36%) and incisional (20%). 10% had BMI > 40 kg/m2, 9% were active smokers and 4% had HbA1c > 8%. 21% of all patients did not meet the preoperative optimization cut-offs at time of diagnosis and those were less likely to undergo hernia repair during the study timeframe compared to those who did (OR 0.50; 95% CI [0.42-0.60]). There was a higher proportion of females (21%) and Blacks (22%) with BMI > 40 kg/m2 compared to males (11%) and other races (11-15%), p = 0.002. As the level of socioeconomic distress increased, there was a corresponding increase in the proportion of patients who did not meet preoperative optimization cut-offs from 16% in prosperous communities to 25% in distressed communities (p < 0.0001). CONCLUSION: Nearly 1 of 5 patients with ventral hernias is affected by commonly used arbitrary preoperative optimization cut-offs. These cut-offs disproportionately impact females, Black patients and those with higher socioeconomic distress. These disparities need to be considered when planning preoperative optimization protocols and resource allocation to ensure equitable access to elective ventral hernia repair.

A narrative review of ergonomic problems, principles, and potential solutions in surgical operations.

BACKGROUND: Ergonomic development and awareness are critical to the long-term health and well-being of surgeons. Work-related musculoskeletal disorders affect an overwhelming majority of surgeons, and various operative modalities (open, laparoscopic, and robotic surgery) differentially affect the musculoskeletal system. Previous reviews have addressed various aspects of surgical ergonomic history or methods of ergonomic assessment, but the purpose of this study is to synthesize ergonomic analysis by surgical modality while discussing future directions of the field based on current perioperative interventions. METHODS: pubmed was queried for "ergonomics," "work-related musculoskeletal disorders," and "surgery," which returned 124 results. From the 122 English-language papers, a further search was conducted via the articles' sources for relevant literature. RESULTS: Ninety-nine sources were ultimately included. Work-related musculoskeletal disorders culminate in detrimental effects ranging from chronic pain and paresthesias to reduced operative time and consideration for early retirement. Underreporting symptoms and a lack of awareness of proper ergonomic principles substantially hinder the widespread utilization of ergonomic techniques in the operating room, reducing the quality of life and career longevity. Therapeutic interventions exist at some institutions but require further research and development for necessary widespread implementation. CONCLUSION: Awareness of proper ergonomic principles and the detrimental effects of musculoskeletal disorders is the first step in protecting against this universal problem. Implementing ergonomic practices in the operating room is at a crossroads, and incorporating these principles into everyday life must be a priority for all surgeons.

The effect of smoking status on inguinal hernia repair outcomes: An ACHQC analysis.

BACKGROUND: Smoking has been shown to negatively affect surgical outcomes, so smoking cessation prior to elective operations is often recommended. However, the effects of smoking status on inguinal hernia repair outcomes have not been extensively studied. Hence, we investigated the association between smoking status and short-term adverse outcomes following inguinal hernia repair. METHODS: Abdominal Core Health Quality Collaborative database was queried for elective, clean inguinal hernia repairs, excluding those with concomitant procedures or where length of stay > 30 days. The resulting cohort was divided into three groups: current smokers, former smokers, and never smokers. Baseline patient, hernia, operative characteristics, and 30-day outcomes were compared. Multivariable logistic regression was used to evaluate the association between smoking status and overall and wound complications. RESULTS: 19,866 inguinal hernia repairs were included (current smokers = 2239, former smokers = 4064 and never smokers = 13,563). Current smokers and former smokers, compared to never smokers, had slightly higher unadjusted rates of overall complication rates (9% and 9% versus 7%, p = 0.003) and surgical site occurrences/infection (6% and 6% versus 4%, p < 0.001). However, on multivariable analysis, compared to current smokers, neither the rates of overall complications nor surgical site occurrences were significantly different in former smokers (OR = 0.93, 95% CI [0.76, 1.13] and OR = 0.92, 95% CI [0.73, 1.17]) and never smokers (OR = 0.99, 95% CI [0.83, 1.18] and OR = 0.86, 95% CI [0.70,1.06]) respectively. CONCLUSIONS: Smoking status is not associated with short-term adverse outcomes following inguinal hernia repair. Mandating smoking cessation does not appear necessary to prevent short-term adverse outcomes.

Entospletinib with decitabine in acute myeloid leukemia with mutant TP53 or complex karyotype: A phase 2 substudy of the Beat AML Master Trial.

BACKGROUND: Patients with acute myeloid leukemia (AML) who have tumor protein p53 (TP53) mutations or a complex karyotype have a poor prognosis, and hypomethylating agents are often used. The authors evaluated the efficacy of entospletinib, an oral inhibitor of spleen tyrosine kinase, combined with decitabine in this patient population. METHODS: This was a multicenter, open-label, phase 2 substudy of the Beat AML Master Trial (ClinicalTrials.gov identifier NCT03013998) using a Simon two-stage design. Eligible patients aged 60 years or older who had newly diagnosed AML with mutations in TP53 with or without a complex karyotype (cohort A; n = 45) or had a complex karyotype without TP53 mutation (cohort B; n = 13) received entospletinib 400 mg twice daily with decitabine 20 mg/m2 on days 1-10 every 28 days for up to three induction cycles, followed by up to 11 consolidation cycles, in which decitabine was reduced to days 1-5. Entospletinib maintenance was given for up to 2 years. The primary end point was complete remission (CR) and CR with hematologic improvement by up to six cycles of therapy. RESULTS: The composite CR rates for cohorts A and B were 13.3% (95% confidence interval, 5.1%-26.8%) and 30.8% (95% confidence interval, 9.1%-61.4%), respectively. The median duration of response was 7.6 and 8.2 months, respectively, and the median overall survival was 6.5 and 11.5 months, respectively. The study was stopped because the futility boundary was crossed in both cohorts. CONCLUSIONS: The combination of entospletinib and decitabine demonstrated activity and was acceptably tolerated in this patient population; however, the CR rates were low, and overall survival was short. Novel treatment strategies for older patients with TP53 mutations and complex karyotype remain an urgent need.

Characterization of the HDAC/PI3K inhibitor CUDC-907 as a novel senolytic.

The accumulation of senescent cells has an important role in the phenotypical changes observed in ageing and in many age-related pathologies. Thus, the strategies designed to prevent these effects, collectively known as senotherapies, have a strong clinical potential. Senolytics are a type of senotherapy aimed at specifically eliminating senescent cells from tissues. Several small molecule compounds with senolytic properties have already been identified, but their specificity and range of action are variable. Because of this, potential novel senolytics are being actively investigated. Given the involvement of HDACs and the PI3K pathway in senescence, we hypothesized that the dual inhibitor CUDC-907, a drug already in clinical trials for its antineoplastic effects, could have senolytic effects. Here, we show that CUDC-907 was indeed able to selectively induce apoptosis in cells driven to senesce by p53 expression, but not when senescence happened in the absence of p53. Consistent with this, CUDC-907 showed senolytic properties in different models of stress-induced senescence. Our results also indicate that the senolytic functions of CUDC-907 depend on the inhibitory effects of both HDACs and PI3K, which leads to an increase in p53 and a reduction in BH3 pro-survival proteins. Taken together, our results show that CUDC-907 has the potential to be a clinically relevant senolytic in pathological conditions in which stress-induced senescence is involved.

The Outcomes of Diffuse Large B-cell Lymphoma Patients with Synchronous and Early Central Nervous System Involvement: A Single-Center Experience.

BACKGROUND: Diffuse large B cell lymphoma (DLBCL) is the most commonly diagnosed subtype of non-Hodgkin's lymphoma (NHL). R-CHOP has significantly improved clinical outcomes in patients with DLBCL, however, its indication in the prevention of CNS relapse and recurrence is still inconsistent. Moreover, prophylactic methotrexate and/or cytarabine have been used prophylactically for DLBCL patients is at high risk of CNS relapse and to treat CNS DLBCL, however, their efficacy remains unclear. METHODS: The aim of our retrospective study was to determine the incidence of CNS in-volvement in patients with DLBCL and to describe its risk factors and survival outcomes. RESULTS: A total of 406 patients with DLBCL were identified, and 17 (4.2%) of DLBCL patients had CNS involvement i.e. 9 (2.2 %) at diagnosis and 8 (~2%) at relapse. The patients were younger, had advanced stage, high CNS-IPI, and had extra nodal involvement. Seven out of the 17 patients who survived received chemotherapy and a prophylactic methotrexate. Considering the CNS-IPI, of the 146 patients with high CNS-IPI at presentation, 18 received the prophylactic HDMTX and 3 (16.7%) of them had CNS relapse. Two (1.6%) out of 128 who did not receive the prophylactic HDMTX had CNS relapse. On the other hand, of the 223 patients with intermediate CNS-IPI, 25 received the prophylactic HDMTX and 2 (8%) of them had CNS relapse and in 198 patients who did not receive the prophylactic HDMTX, 2 (1.01%) had CNS relapse. The 5-year progression-free survival and overall survival rates for the entire cohort were 73% and 84%, respectively. The median OS for those who had CNS involvement was 17 months and the 2-year OS was 40%. CONCLUSION: CNS involvement in DLBCL has a poor prognosis, thus, aggressive CNS-directed therapy should be considered, especially in young patients.

Pericardial Effusion: A Novel Presentation of Aplastic Anemia.

Pericardial effusion is defined as the accumulation of fluid between the visceral and parietal pericardium. The underlying etiology varies as any pathology that causes pericarditis or involves the pericardium can cause effusion. In practice, the majority of pericarditis cases are idiopathic, although these are assumed to be secondary to occult viral infection or inflammatory phenomena. Malignancy, particularly the metastatic spread of noncardiac primary tumors, has been implicated as a differential in the diagnosis of pericardial effusion. Though commonly seen in solid malignancies, effusion has been reported in hematologic malignancies such as myelodysplastic syndrome (MDS), acute leukemia, and lymphoma. Nonetheless, pericardial effusions associated with hematologic conditions are extremely rare with only one case report published describing pericardial effusion secondary to immune thrombocytopenia (ITP). We herein report the first documented case, to our knowledge, of pericardial effusion as an initial clinical manifestation of aplastic anemia in a middle-aged male presenting with pancytopenia.

Process for quality assessment review of societal guidelines-an editorial to accompany "multi-society consensus conference and guideline on the treatment of gastroesophageal reflux disease (GERD)".

BACKGROUND: The SAGES Guidelines Committee has implemented processes for Quality Assessment of SAGES-endorsed guidelines, with the aim of improving the quality of published guidelines. METHODS: We provide details of the processes developed, using standardized tools for assessing the methodological quality of practice guidelines. As an example, we describe the application of our processes to the recent multi-societal GERD consensus guideline. RESULTS: Assessment of the multi-societal GERD consensus guideline by the iterative processes of SAGES Quality Assurance taskforce improved the quality of the final manuscript in all domains of appraisal. These processes are easily applicable to future guidelines. CONCLUSIONS: Such systems will increase the confidence in SAGES recommendations and increase the implementation of SAGES guidelines. By demonstrating the rigor of Quality Assessment, this confidence also extends to a further increase in the assurance of the publications of the Surgical Endoscopy journal.