A History of The Texas Education Agency Instructional Facility Allotment (IFA) Program in Hidalgo County School Districts Located in The Texas Rio Grande Valley from 1997 to 2007

This study examines the implementation of the Texas Education Agency (TEA) Instructional Facility Allotment (IFA) Program in the Rio Grande Valley (RGV) through documentation chronicling Hidalgo County school districts from 1997 through 2007 that secured IFA & EDA monies to build new facilities. Participants in this study included Hidalgo County school districts, three school architects, ten Hidalgo County school district superintendents and one Texas state senator. The fifteen school district superintendents were asked to complete an Instructional Facility Allotment (IFA) and Existing Debt Allotment (EDA) survey. The three architects, ten superintendents and state senator were interviewed in order to provide school facility conditions before and after the implementation of the IFA program. Based on the superintendent interviews four emerging themes were documented. Ex post facto data from the Texas Education Agency (TEA) Academic Excellence Indicator System (AEIS) website was reported in order to address the IFA program components. Collectively this information was compiled and analyzed to produce research findings

A Multi-Institutional Analysis of Elderly Patients Undergoing a Liver Resection for Intrahepatic Cholangiocarcinoma

BACKGROUND: Little is known regarding postoperative outcomes of elderly patients undergoing liver surgery for intrahepatic cholangiocarcinoma (ICC). METHODS: Five hundred and eighty-four patients undergoing liver resection for ICC between 1990 and 2015 were identified. Perioperative morbidity, mortality, overall survival (OS), and disease-free survival (DFS) were compared between elderly (>70 year, n = 129) and non-elderly (≤70 years, n = 455) patients. RESULTS: Older patients had a higher incidence of complications (elderly vs. non-elderly; 52.7% vs. 42.6%; P = 0.03), as well as major complications (elderly vs. non-elderly; 24.0% vs. 14.9%; P = 0.01); 30-day (0.1% vs. 3.3%; P > 0.05), and 90-day mortality (2.3% vs. 5.5%; P > 0.05) were comparable. Five-year OS and DFS were comparable between the elderly and non-elderly patients (OS, 13.3% vs. 24.4%; and DFS; 7.3% vs. 12.0%; P > 0.05). On propensity score matching, DFS and OS were also comparable among non-elderly versus elderly patients. Poor tumor grade was associated with worse DFS among elderly patients (HR = 1.6, 95%CI 1.0-2.6; P = 0.04), whereas periductal invasion (HR = 1.9, 95% CI 1.1-3.5; P = 0.03) and nodal disease (HR = 2.3, 95% CI 1.3-3.9; P = 0.003) were predictive of shorter DFS among non-elderly patients. CONCLUSION: Elderly patients undergoing liver surgery for ICC demonstrated an increased risk of perioperative complications, but comparable long-term DFS and OS compared with younger patients. Rather, tumor characteristics were more predictive of worse long-term outcomes.info:eu-repo/semantics/publishedVersio

Improving psychosocial outcomes for caregivers of people with poor prognosis gastrointestinal cancers: a randomized controlled trial (Family Connect)

Abstract Purpose This study investigated the effectiveness of a structured telephone intervention for caregivers of people diagnosed with poor prognosis gastrointestinal cancer to improve psychosocial outcomes for both caregivers and patients. Methods Caregivers of patients starting treatment for upper gastrointestinal or Dukes D colorectal cancer were randomly assigned (1:1) to the Family Connect telephone intervention or usual care. Caregivers in the intervention group received four standardized telephone calls in the 10 weeks following patient hospital discharge. Caregivers' quality of life (QOL), caregiver burden, unmet supportive care needs and distress were assessed at 3 and 6 months. Patients' QOL, unmet supportive care needs, distress and health service utilization were also assessed at these time points. Results Caregivers (128) were randomized to intervention or usual care groups. At 3 months, caregiver QOL scores and other caregiver-reported outcomes were similar in both groups. Intervention group participants experienced a greater sense of social support (p=.049) and reduced worry about finances (p=.014). Patients whose caregiver was randomized to the intervention also had fewer emergency department presentations and unplanned hospital readmissions at 3 months post-discharge (total 17 vs. 5, p=.01). Conclusions This standardized intervention did not demonstrate any significant improvements in caregiver well-being but did result in a decrease in patient emergency department presentations and unplanned hospital readmissions in the immediate post-discharge period. The trend towards improvements in a number of caregiver outcomes and the improvement in health service utilization support further development of telephone-based caregiver-focused supportive care interventions

Liver transplantation is a preferable alternative to palliative therapy for selected patients with advanced hepatocellular carcinoma

Background: Patients with hepatocellular carcinoma (HCC) beyond the traditional criteria (advanced HCC) are typically offered palliation, which is associated with a 3-year survival rate lower than 30%. This study aimed to describe the outcomes for a subset of patients with advanced HCC who satisfied the Extended Toronto Criteria (ETC) and were listed for liver transplantation (LT). Materials & Methods: All patients listed in the Toronto liver transplant program with HCC beyond both the Milan and University of California, San Francisco criteria were included in this study. Data were extracted from the prospectively collected electronic database. All radiological images were reviewed by two independent radiologists. The primary endpoint was patient survival. Results: Between January 1999 and August 2014, 96 patients with advanced HCC were listed for LT, and 62 (65%) of these patients received bridging therapy while on the waiting list. Bridging therapy led to a significant reduction in tumor progression (p=0.02) and tumor burden (p <0.001). The majority of those listed underwent LT (n=69, 72%). Both tumor progression on waiting list (HR 4.973 [1.599 – 15.464], p=0.006) and peak AFP ≥400ng/ml (HR 4.604 [1.660 – 12.768], p=0.003) were independently associated with waiting list dropout. Post-LT HCC recurrence occurred in 35% (n=24). Among those with HCC recurrence, survival was significantly better for those who received curative treatment (p=0.004). The overall actuarial survival rates from the listing were 76% at 1 year, 56% at 3 years, and 47% at 5 years, and the corresponding rates from LT were 93%, 71%, and 66%. Conclusion: LT provides significantly better survival rates than palliation for patients with selected advanced HCC

Identification of unique neoantigen qualities in long-term survivors of pancreatic cancer

Pancreatic ductal adenocarcinoma is a lethal cancer with fewer than 7% of patients surviving past 5 years. T-cell immunity has been linked to the exceptional outcome of the few long-term survivors1,2, yet the relevant antigens remain unknown. Here we use genetic, immunohistochemical and transcriptional immunoprofiling, computational biophysics, and functional assays to identify T-cell antigens in long-term survivors of pancreatic cancer. Using whole-exome sequencing and in silico neoantigen prediction, we found that tumours with both the highest neoantigen number and the most abundant CD8+ T-cell infiltrates, but neither alone, stratified patients with the longest survival. Investigating the specific neoantigen qualities promoting T-cell activation in long-term survivors, we discovered that these individuals were enriched in neoantigen qualities defined by a fitness model, and neoantigens in the tumour antigen MUC16 (also known as CA125). A neoantigen quality fitness model conferring greater immunogenicity to neoantigens with differential presentation and homology to infectious disease-derived peptides identified long-term survivors in two independent datasets, whereas a neoantigen quantity model ascribing greater immunogenicity to increasing neoantigen number alone did not. We detected intratumoural and lasting circulating T-cell reactivity to both high-quality and MUC16 neoantigens in long-term survivors of pancreatic cancer, including clones with specificity to both high-quality neoantigens and predicted cross-reactive microbial epitopes, consistent with neoantigen molecular mimicry. Notably, we observed selective loss of high-quality and MUC16 neoantigenic clones on metastatic progression, suggesting neoantigen immunoediting. Our results identify neoantigens with unique qualities as T-cell targets in pancreatic ductal adenocarcinoma. More broadly, we identify neoantigen quality as a biomarker for immunogenic tumours that may guide the application of immunotherapies

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P &lt; 0.001) and PARP inhibitor therapy (P &lt; 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P &lt; 0.018) and WEE1 inhibitor (P &lt; 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P &lt; 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

Research priorities in prehabilitation for patients undergoing cancer surgery: an international Delphi study

Background Recently, the number of prehabilitation trials has increased significantly. The identification of key research priorities is vital in guiding future research directions. Thus, the aim of this collaborative study was to define key research priorities in prehabilitation for patients undergoing cancer surgery. Methods The Delphi methodology was implemented over three rounds of surveys distributed to prehabilitation experts from across multiple specialties, tumour streams and countries via a secure online platform. In the first round, participants were asked to provide baseline demographics and to identify five top prehabilitation research priorities. In successive rounds, participants were asked to rank research priorities on a 5-point Likert scale. Consensus was considered if > 70% of participants indicated agreement on each research priority. Results A total of 165 prehabilitation experts participated, including medical doctors, physiotherapists, dieticians, nurses, and academics across four continents. The first round identified 446 research priorities, collated within 75 unique research questions. Over two successive rounds, a list of 10 research priorities reached international consensus of importance. These included the efficacy of prehabilitation on varied postoperative outcomes, benefit to specific patient groups, ideal programme composition, cost efficacy, enhancing compliance and adherence, effect during neoadjuvant therapies, and modes of delivery. Conclusions This collaborative international study identified the top 10 research priorities in prehabilitation for patients undergoing cancer surgery. The identified priorities inform research strategies, provide future directions for prehabilitation research, support resource allocation and enhance the prehabilitation evidence base in cancer patients undergoing surgery

DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association

Here we report the DNA methylation profile of 84 sporadic pancreatic neuroendocrine tumors (PanNETs) with associated clinical and genomic information. We identified three subgroups of PanNETs, termed T1, T2 and T3, with distinct patterns of methylation. The T1 subgroup was enriched for functional tumors and ATRX, DAXX and MEN1 wild-type genotypes. The T2 subgroup contained tumors with mutations in ATRX, DAXX and MEN1 and recurrent patterns of chromosomal losses in half of the genome with no association between regions with recurrent loss and methylation levels. T2 tumors were larger and had lower methylation in the MGMT gene body, which showed positive correlation with gene expression. The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs

Vascular biliopathy as a cause of common bile duct obstruction successfully treated by mesocaval shunt and endoscopic retrograde cholangiopancreatography biliary stent placement

Common bile duct stenosis owing to extrahepatic portal varices is termed "portal hypertensive biliopathy" (PHB) and is a rare occurrence. We report a case of PHB owing to portal vein thrombosis with cavernous transformation successfully managed by mesocaval shunt and endoscopic retrograde cholangiopancreatography (ERCP) biliary stent placement. A 44-year-old male, who presented with hematemesis, melena, jaundice, and abdominal pain, underwent gastroscopy, which revealed bleeding gastric varices. Computed tomography with arterial and venous imaging demonstrated portal vein thrombosis with cavernous transformation and extensive extrahepatic varices within the porta hepatis causing common bile duct obstruction from extrinsic compression. Biliary decompression was achieved with ERCP, and a small common bile duct stone was retrieved. A mesocaval shunt with a 16 mm Dacron graft successfully treated the portal hypertension. PHB is rare. We report a case successfully treated by mesocaval shunt and ERCP.3 page(s

Distributive justice during the coronavirus disease 2019 pandemic in Australia

Distributive justice refers to the fair and appropriate distribution of benefits, risks and costs within a society. In a medical context, this requires patients with similar cases to be treated in a similar manner, and for there to be overarching equality of access to finite health resources. Distributive justice is a derivative of the broader principle of justice, which is one of the four biomedical ethics pillars described by Beauchamp and Childress as underpinning modern medical practice, along with beneficence, non‐maleficence and autonomy.1 The concept of distributive justice as it relates to the delivery of surgical care requires attention in the context of the coronavirus disease 2019 (COVID‐19) pandemic. Significant measures have been taken by our governments, health ministries and public and private hospitals in an effort to prepare the Australian healthcare system for high volumes of patients with COVID‐19. In the Australian context where a relatively low societal burden of disease has emerged, a question arises about the opportunity cost of these unprecedented interventions and restrictions, which have resulted in significant disruptions to the delivery of emergency and elective medical treatment – are we upholding the principle of distributive justice during the present pandemic