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Introduction: Patients with metastatic colorectal cancer (mCRC) often require multidisciplinary interventions due to the diversity of symptoms. Palliative treatment offers benefits including improved quality of life, yet sociodemographic disparities influence its utilization. This study aims to characterize these disparities in palliative treatment use among mCRC patients., Methods: Utilizing data from the National Cancer Database, we identified patients diagnosed with mCRC between 2016 and 2020. Patients were categorized by metastatic site: peritoneal, liver, lung, or bone/brain/lymph node. Palliative treatment rates were compared across metastatic sites as well as patient and hospital factors., Results: A total of 106,241 patients were identified as having mCRC, with 19,208 (18.08%) receiving palliative treatment; 24.0% of patients with multiple metastatic disease and 14.0% of those with solely peritoneal metastases (PM) utilized palliative treatment (p < 0.001). Furthermore, patients over 75 years of age had a significantly decreased likelihood of receiving palliative treatment compared with younger patients (p = 0.0002). Hispanic patients did not differ significantly from non-Hispanic White populations (p = 0.47). Those in the highest education quartile demonstrated a higher degree of palliative treatment use compared with the lowest education quartile (p = 0.0081)., Conclusion: Among patients with mCRC, those with multiple sites of metastatic disease tend to receive higher rates of palliative treatment compared with those with oligometastatic disease. Patients with PM had the lowest rate of receiving palliative treatment. Other determinates of utilizing palliative treatment include younger age groups and higher education. Further research is warranted to understand the patterns of disparities in palliative treatment use among mCRC patients., Competing Interests: Disclosures: Shaina Sedighim, Rhami Khorfan, Jordan Shin, Aaqil Khan, Yixuan Irene Tang, Amy Y. Li, Maheswari Senthil, Michael P. O’Leary, and Oliver S. Eng have no relevant conflicts of interest to declare that may be relevant to the contents of this study., (© 2024. Society of Surgical Oncology.)

Efficient DNA double strand break (DSB) repair is necessary for genomic stability and determines efficacy of DNA damaging cancer therapeutics. Spatiotemporal dynamics and post-translational modifications of repair proteins at DSBs dictate repair efficacy. Here, we identified a non-canonical function of GCN5 in regulating both HR and NHEJ repair post genotoxic stress. Mechanistically, genotoxic stress induced GCN5 recruitment to DSBs. GCN5 PARylation by PARP1 was essential for its recruitment, acetyltransferase activity and DSB repair function. Liquid chromatography-mass spectrometry (LC-MS) identified DNA-PKcs as part of GCN5 interactome. In-vitro acetyltransferase assays revealed that GCN5 acetylates DNA-PKcs at K3241 residue, a prerequisite for DNA-PKcs S2056 phosphorylation and DSB recruitment. Alongside, ChIP-qPCR revealed GCN5 mediates transcription of PRKDC via H3K27Ac acetylation in its promoter region (- 710 to - 554). Genetic perturbation of GCN5 also decreased CHEK1, NBN1, TP53BP1, POL-L transcription and abrogated ATM, BRCA1 activation. Accordingly, GCN5 loss led to persistent ɣ-H2AX foci formation, compromised in-vivo HR-NHEJ and caused GBM radio-sensitization. Importantly, PARP1 inhibition phenocopied GCN5 loss. Together, this study identifies an untraversed DSB repair function of GCN5 and provides mechanistic insights into transcriptional as well as post-translational regulation of pivotal HR-NHEJ factors. Alongside, it highlights the translational importance of PARP1-GCN5 axis in mediating GBM radio-resistance., (© 2024. The Author(s).)

Background: Bariatric surgery is one of the clinical pathways of the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) Masters Program, and laparoscopic adjustable gastric banding (LAGB) is one of the three anchoring bariatric procedures. To improve surgeon lifelong learning, the Masters Program seeks to identify sentinel articles of each of the 3 bariatric anchoring procedures. In this article, we present the top 10 articles on LAGB., Methods: A systematic literature search of papers on LAGB was completed, and publications with the most citations and citation index were selected and shared with SAGES Metabolic and Bariatric Surgery Committee members for review. The individual committee members then ranked these papers, and the top 10 papers were chosen based on the composite ranking., Results: The top 10 sentinel publications on LAGB contributed substantially to the body of literature related to the procedure, whether for surgical technique, novel information, or outcome analysis. A summary of each paper including expert appraisal and commentary is presented here., Conclusion: These seminal articles have had significant contribution to our understanding and appreciation of the LAGB procedure. Bariatric surgeons should use this resource to enhance their continual education and acquisition of specialized skills., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Among many nanoparticle-based delivery platforms, liposomes have been particularly successful with many formulations passed into clinical applications. They are well-established and effective gene and/or drug delivery systems, widely used in cancer therapy including breast cancer. In this review we discuss liposome design with the targeting feature and triggering functions. We also summarise the recent progress (since 2014) in liposome-based therapeutics for breast cancer including chemotherapy and gene therapy. We finally identify some challenges on the liposome technology development for the future clinical translation.

Background: Patients with borderline resectable pancreatic cancer are at high risk of incomplete resection with upfront surgery. Currently, no standard induction chemotherapy regimen exists for these patients. Both FOLFIRINOX (5-FU, irinotecan, & oxaliplatin) and gemcitabine plus nab-paclitaxel (GnP) have shown better efficacy than gemcitabine alone in advanced pancreatic cancer. The current study aims to assess outcomes of real-world patients with borderline resectable pancreatic cancer who received induction FOLFIRINOX or GnP., Methods: In this population-based multicenter retrospective cohort study, patients with biopsy-proven borderline resectable pancreatic cancer diagnosed from 2011 to 2017, in the province of Saskatchewan, Canada, who received FOLFIRINOX or GnP were assessed. Kaplan Meier methods and log rank tests were performed for survival analyses., Results: Of 161 patients with pancreatic cancer who received FOLFIRINOX or GnP during the study period, 20 eligible patients with borderline resectable pancreatic cancer were identified. Ten patients each received FOLFIRINOX or GnP. Eleven patients had partial response (5, FOLFIRINOX; 6, GnP); 3 progressed during treatment. Five patients (4, FOLFIRINOX; 1, GnP; p = NS) underwent curative surgery. The median progression-free survival was 17 months in FOLFIRINOX (95% CI, 5.3-28.6) vs. 9 months (95% CI, 3.0-15) in GnP groups (p = 0.27). Overall, 80% patients in GnP vs. 40% in FOLFIRINOX died from progressive disease. The median overall survival has not been reached in FOLFIRINOX group versus 16 months (95% CI, 9.3-22.7) in GnP group (p = 0.15)., Conclusion: The current study suggests that patients with borderline resectable pancreatic cancer who received FOLFIRINOX tend to have better outcomes. Future studies are warranted to establish a preferred systemic therapy for patients with borderline resectable pancreatic cancer.

Background: Non-elective cholecystectomies can lead to severe postoperative complications and mortality. Existing risk prediction tools do not meet the need to reliably predict these complications., Methods: Using the 2011-2016 American College of Surgeons National Surgical Quality Improvement Program datasets, we identified patients undergoing non-elective cholecystectomy with primary ICD 9/10 codes indicating the following diagnoses: symptomatic cholelithiasis, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and cholangitis. We randomly allocated patients to derivation and validation cohorts (80/20 split). Severe complications (Clavien-Dindo grades IV and V) included unplanned intubation, prolonged mechanical ventilation, pulmonary embolism, acute renal failure requiring dialysis, stroke, myocardial infarction, cardiac arrest, septic shock, and mortality. Logistic regression using backward selection identified predictors of severe complications and a risk score was generated based on this model., Results: Of 68,953 patients in the derivation cohort, 1.7% (N = 1157) suffered severe complications. The final multivariable risk score model included the following predictors: age (0-12 points), preoperative sepsis (5 points), planned open procedure (5 points), estimated glomerular filtration rate (0-13 points), and preoperative albumin level (0-8 points). The associated risk-score model yielded scores from 0 to 43 with 0.1-59.4% predicted probability of severe complications and had a C-statistic of 0.845 (95% CI 0.834, 0.857) in the derivation cohort and 0.870 (95% CI 0.851, 0.889) in the validation cohort., Conclusion: A simple risk-score model predicts severe complications in patients undergoing unplanned cholecystectomy for common indications encountered in an acute care surgery service and identifies high-risk patients.

The incidence of Hepatitis A virus (HAV) among the general population in the United States has decreased by over 95% since the introduction of HAV vaccination in 1995. However, 10% of all new HAV infections occur among men who have sex with men (MSM). However routine HAV is not part of standard of care for provision of PrEP services. Retrospective cohort analysis of MSM assessed for HIV prevention services between 1/1/2016 and 6/30/2017 to evaluate the rates of screening for anti-HAV seroprevalence and subsequent vaccination. HAV IgG was drawn on 96% (96/100) of the patients with 58% (56/96) of patients demonstrating serologic immunity. Of the 40 patients without evidence of immunity, 77% (29/40) returned for a subsequent visit, 48% (14/29) were provided HAV vaccination, and 29% (4/14) received at least two doses. Only 35% (14/40) of patients without documented immunity received HAV vaccination. Visits for PrEP initiation and monitoring in MSM patients are potential opportunities for ensuring HAV vaccination among this high-risk patient population. Public health agencies could optimize HAV vaccination of the high risk MSM by incorporating HAV screening into national PrEP guidelines.

Purpose: The study aims to test the hypothesis that platelet-rich plasma (PRP) stimulates cellular processes involved in endometrial regeneration relevant to clinical management of poor endometrial growth or intrauterine scarring., Methods: Human endometrial stromal fibroblasts (eSF), endometrial mesenchymal stem cells (eMSC), bone marrow-derived mesenchymal stem cells (BM-MSC), and Ishikawa endometrial adenocarcinoma cells (IC) were cultured with/without 5% activated (a) PRP, non-activated (na) PRP, aPPP (platelet-poor-plasma), and naPPP. Treatment effects were evaluated with cell proliferation (WST-1), wound healing, and chemotaxis Transwell migration assays. Mesenchymal-to-epithelial transition (MET) was evaluated by cytokeratin and vimentin expression. Differential gene expression of various markers was analyzed by multiplex Q-PCR., Results: Activated PRP enhanced migration of all cell types, compared to naPRP, aPPP, naPPP, and vehicle controls, in a time-dependent manner (p < 0.05). The WST-1 assay showed increased stromal and mesenchymal cell proliferation by aPRP vs. naPRP, aPPP, and naPPP (p < 0.05), while IC proliferation was enhanced by aPRP and aPPP (p < 0.05). There was no evidence of MET. Expressions of MMP1, MMP3, MMP7, and MMP26 were increased by aPRP (p < 0.05) in eMSC and eSF. Transcripts for inflammation markers/chemokines were upregulated by aPRP vs. aPPP (p < 0.05) in eMSC and eSF. No difference in estrogen or progesterone receptor mRNAs was observed., Conclusions: This is the first study evaluating the effect of PRP on different human endometrial cells involved in tissue regeneration. These data provide an initial ex vivo proof of principle for autologous PRP to promote endometrial regeneration in clinical situations with compromised endometrial growth and scarring.

Objective: Adenomyosis is a clinical disorder defined by the presence of endometrial glands and stroma within the myometrium, the pathogenesis of which is poorly understood. We postulate that dysregulation of genes and pathways in eutopic endometrium may predispose to ectopic implantation. No study, to our knowledge, has examined the global transcriptome of isolated eutopic endometrium from women with clinically significant adenomyosis., Design: Laboratory-based study with full institutional review board approval and consents., Material and Methods: Endometrial sampling was performed on hysterectomy specimens (proliferative phase) from symptomatic women with pathologically confirmed diffuse adenomyosis (n = 3). Controls (n = 5) were normo-ovulatory patients without adenomyosis. All patients were free from leiomyoma, endometriosis, and hormonal exposures. Isolated purified total RNA was subjected to microarray analysis using the Gene 1.0 ST Affymetrix platform. Data were analyzed with GeneSpring and Ingenuity Pathway analysis. Validation of several genes was undertaken by quantitative real-time reverse transcriptase polymerase chain reaction., Results: Comparison of transcriptomes of proliferative endometrium from women with and without adenomyosis revealed 140 upregulated and 884 downregulated genes in samples from women with adenomyosis compared to controls. Highly differentially expressed genes include those involved in regulation of apoptosis, steroid hormone responsiveness, and proteins involved in extracellular matrix remodeling as well as microRNAs of unknown significance. Affected canonical pathways included eukaryotic initiation factor 2 signaling, oxidative phosphorylation, mitochondrial dysfunction, estrogen receptor signaling, and mammalian target of rapamycin signaling., Conclusion: The eutopic endometrium in patients with adenomyosis has fundamental abnormalities that may predispose to invasion and survival beyond the myometrial interface., (© The Author(s) 2016.)

Paraprofessional medical assistants (MAs) could help to promote pediatric primary care as a source of mental health services, particularly among patient populations who receive disparate mental health care. This project piloted a brief training to enhance the ability of MAs to have therapeutic encounters with Latino families who have mental health concerns in pediatric primary care. The evaluation of the pilot found that MAs were able to master most of the skills taught during the training, which improved their ability to have patient-centered encounters with families during standardized patient visits coded with the Roter Interaction Analysis System. Parents interviewed 1 and 6 months following the training were more than twice as willing as parents interviewed 1 month before the training to discuss mental health concerns with MAs, and they had better perceptions of their interactions with MAs (all p < 0.01) even after controlling for a range of patient and visit characteristics. Before training, 10.2% of parents discussed a mental health concern with the MA but not the physician; this never happened 6 months after training. This pilot provides preliminary evidence that training MAs holds potential to supplement other educational and organizational interventions aimed at improving mental health services in pediatric primary care, but further research is necessary to test this type of training in other settings and among different patient populations.