The psychosocial impact of prostate cancer screening for BRCA1 and BRCA2 carriers.

OBJECTIVES: To report the long-term outcomes from a longitudinal psychosocial study that forms part of the 'Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted Screening in men at higher genetic risk and controls' (IMPACT) study. The IMPACT study is a multi-national study of targeted prostate cancer (PrCa) screening in individuals with a known germline pathogenic variant (GPV) in either the BReast CAncer gene 1 (BRCA1) or the BReast CAncer gene 2 (BRCA2). SUBJECTS AND METHODS: Participants enrolled in the IMPACT study were invited to complete a psychosocial questionnaire prior to each annual screening visit for a minimum of 5 years. The questionnaire included questions on sociodemographics and the following measures: Hospital Anxiety and Depression Scale, Impact of Event Scale, 36-item Short-Form Health Survey, Memorial Anxiety Scale for PrCa, Cancer Worry Scale, risk perception and knowledge. RESULTS: A total of 760 participants completed questionnaires: 207 participants with GPV in BRCA1, 265 with GPV in BRCA2 and 288 controls (non-carriers from families with a known GPV). We found no evidence of clinically concerning levels of general or cancer-specific distress or poor health-related quality of life in the cohort as a whole. Individuals in the control group had significantly less worry about PrCa compared with the carriers; however, all mean scores were low and within reported general population norms, where available. BRCA2 carriers with previously high prostate-specific antigen (PSA) levels experience a small but significant increase in PrCa anxiety (P = 0.01) and PSA-specific anxiety (P < 0.001). Cancer risk perceptions reflected information provided during genetic counselling and participants had good levels of knowledge, although this declined over time. CONCLUSION: This is the first study to report the longitudinal psychosocial impact of a targeted PrCa screening programme for BRCA1 and BRCA2 carriers. The results reassure that an annual PSA-based screening programme does not have an adverse impact on psychosocial health or health-related quality of life in these higher-risk individuals. These results are important as more PrCa screening is targeted to higher-risk groups.

Cholestasis alters polarization and suppressor function of hepatic regulatory T cells.

Fibrosing cholangiopathies, including biliary atresia and primary sclerosing cholangitis, involve immune-mediated bile duct epithelial injury and hepatic bile acid (BA) retention (cholestasis). Regulatory T-cells (Tregs) can prevent auto-reactive lymphocyte activation, yet the effects of BA on this CD4 lymphocyte subset are unknown. Gene regulatory networks for hepatic CD4 lymphocytes in a murine cholestasis model revealed Tregs are polarized to Th17 during cholestasis. Following bile duct ligation, Stat3 deletion in CD4 lymphocytes preserved hepatic Treg responses. While pharmacological reduction of hepatic BA in MDR2-/- mice prompted Treg expansion and diminished liver injury, this improvement subsided with Treg depletion. A cluster of patients diagnosed with biliary atresia showed both increased hepatic Treg responses and improved 2-year native liver survival, supporting that Tregs might protect against neonatal bile duct obstruction. Together, these findings suggest liver BA determine Treg function and should be considered as a therapeutic target to restore protective hepatic immune responses.

The role of specialist palliative care in individuals "living beyond cancer": a narrative review of the literature.

PURPOSE: Many patients living beyond cancer experience significant unmet needs, although few of these patients are currently reviewed by specialist palliative care teams (SPCTs). The aim of this narrative review was to explore the current and potential role of SPCTs in this cohort of patients. METHODS: A search strategy was developed for Medline, and adapted for Embase, CINAHL, and PsycInfo. Additionally, websites of leading oncology, cancer survivorship, and specialist palliative care organisations were examined. The focus of the search was on individuals living beyond cancer rather than other groups of cancer survivors. RESULTS: 111 articles were retrieved from the search for full text review, and 101 other sources of information were identified after hand searching the reference lists of the full text articles, and the aforesaid websites. The themes of the review encompass the definition of palliative care/specialist palliative care, current models of specialist palliative care, core activities of SPCTs, relevant expertise of SPCTs, and potential barriers to change in relation to extending their support and expertise to individuals living beyond cancer. The review identified a paucity of evidence to support the role of SPCTs in the management of patients living beyond cancer. CONCLUSIONS: Individuals living beyond cancer have many unmet needs, and specific services are required to manage these problems. Currently, there is limited evidence to support the role of specialist palliative care teams in the management of this cohort of people, and several potential barriers to greater involvement, including limited resources, and lack of relevant expertise.

Same People, Different Results: Categorizing Cancer Registry Cases Across the Rural-Urban Continuum.

BACKGROUND: Many rural-urban indexes are utilized in cancer research. This variation introduces inconsistencies between studies. Recommendations on index use have prioritized geographical unit over feasibility of inclusion in analysis. We evaluated rural-urban indexes and recommend one for use to increase comparability across studies. METHODS: We assessed 9 US rural-urban indexes regarding their respective rural and urban code ranges; geographical unit, land area, and population distributions; percent agreement; suitability for analysis; and integration feasibility for national, state, and local cancer research. We referenced 1569 Wisconsin Pancreatic Cancer Registry patients to demonstrate how index choice affects patient categorization. RESULTS: Six indexes categorized rural and urban areas. Indexes agreed on binary rural-urban designation for 88.8% of the US population. As ternary variables, they agreed for 83.4%. For cancer registry patients, this decreased to 73.4% and 60.4% agreement, respectively. Rural-Urban Continuum Codes (RUCC) performed the best in differentiating metropolitan, micropolitan, and rural counties; availability for retrospective and prospective studies; and continuous coding for analysis. CONCLUSIONS: Urban/rural patient categorization changed with index selection. We conclude that RUCC is an appropriate and feasible rural-urban index to include in cancer research, as it is standardly available in national cancer registries, can be matched to patient's county of residence for local research, and it had the least amount of fluctuation of the indices analyzed. Utilizing RUCC as a continuous variable across studies with a rural-urban component will increase reproducibility and comparability of results and eliminate rural-urban index choice as a potential source of discrepancy between studies.

Comparison of Shelf-stable and Conventional Resuscitation Products in a Canine Model of Hemorrhagic Shock.

INTRODUCTION: Treatment of severe hemorrhagic shock typically involves hemostatic resuscitation with blood products. However, logistical constraints often hamper the wide distribution of commonly used blood products like whole blood. Shelf-stable blood products and blood substitutes are poised to be able to effectively resuscitate individuals in hemorrhagic shock when more conventional blood products are not readily available. METHODS: Purpose-bred adult dogs (n = 6) were anesthetized, instrumented, and subjected to hemorrhagic shock (MAP <50 mmHg or 40% blood volume loss). Then each dog was resuscitated with one of five resuscitation products: (1) lactated ringers solution and hetastarch (LRS/heta), (2) canine chilled whole blood (CWB), (3) fresh frozen plasma (FFP) and packed red blood cells (pRBC), (4) canine freeze-dried plasma (FDP) and hemoglobin-based oxygen carrier (HBOC), or (5) HBOC/FDP and canine lyophilized platelets (LyoPLT). Each dog was allowed to recover after the hemorrhage resuscitation event and was then subjected to another hemorrhage event and resuscitated with a different product until each dog was resuscitated with each product. RESULTS: At the time when animals were determined to be out of shock as defined by a shock index <1, MAP (mm Hg) values (mean ± standard error) were higher for FFP/pRBC (n = 5, 83.7 ± 4.5) and FDP/HBOC+LyoPLT (n = 4, 87.8. ± 2.1) as compared to WB (n = 4, 66.0 ± 13.1). A transient increase in creatinine was seen in dogs resuscitated with HBOC and FDP. Albumin and base excess increased in dogs resuscitated with HBOC and FDP products compared to LRS/heta and CWB (p < 0.01). CONCLUSION: Combinations of shelf-stable blood products compared favorably to canine CWB for resolution of shock. Further research is needed to ascertain the reliability and efficacy of these shelf-stable combinations of products in other models of hemorrhage that include a component of tissue damage as well as naturally occurring trauma. LEVEL OF EVIDENCE: This is a Therapeutic/Care management study with Level of Evidence IV.

Implementation of a Multicomponent Medication Adherence Promotion System is Associated with a Decrease in Late T-cell Mediated Rejection.

Poor immunosuppression adherence in pediatric liver transplant (LT) recipients contributes to late T-cell mediated rejection (TCMR) in approximately 90% of cases and increases the risk of mortality. A Medication Adherence Promotion System (MAPS) was found to reduce late rejection in pediatric kidney transplant recipients. Utilizing quality improvement methodology, we adapted and implemented the MAPS in our LT clinic. Our primary outcome was population level rates of late TCMR, measured as a monthly incident rate. Three-hundred fourteen LT patients are currently cared for at our institution. One-hundred sixty-two (52%) are females with a median age of 16 years old and a median age at LT of 2 years. Pre-implementation, monthly rejection rates were 0.84 rejections per 100 patient-months. After iterative implementation of MAPS over 2.3 years, monthly rejection rates decreased to 0.46 rejections per 100 patient-months, a 45% decrease in late TCMR. Implementation of MAPS was associated with a sustained 45% decrease TCMR at a single center, suggesting that quality improvement tools may help improve clinical outcomes. MAPS may be an important tool to ensure long-term allograft health. Future studies should rigorously test MAPS across a multi-center sample.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

Background: Liver fibrosis is an important clinical endpoint of progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. Objective: To assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. Methods: This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD [primary sclerosing cholangitis (PSC), ASC (autoimmune sclerosing cholangitis), or AIH (autoimmune hepatitis)]. The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within a 6-month interval. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (kPa) for each examination. Laboratory markers of liver fibrosis [aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 score (FIB-4)] were recorded. For investigational purposes, one pathologist determined histologic METAVIR liver fibrosis stage, blinded to clinical and MRI data. Spearman rank-order correlation was calculated between MRE liver stiffness and METAVIR liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating METAVIR F0-F1 from F2-F4 fibrosis), calculating sensitivity and specificity at the Youden's index. Results: The study included 46 patients (median [IQR] age, 16.6 [13.7-17.8] years; 20 female, 26 male); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR: 2.2-4.0 kPa). MRE liver stiffness and METAVIR fibrosis stage showed strong positive correlation (rho=0.68). For identifying advanced liver fibrosis, MRE liver stiffness had AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had AUC of 0.72, with sensitivity of 60.0% and specificity of 85.0%; and FIB-4 had AUC of 0.71, with sensitivity of 64.0% and 85.0%. Conclusion: MRE liver stiffness measurements were associated with histologic liver fibrosis severity. Clinical Impact: The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD.

Distinct effects of racial and socioeconomic disparities on biliary atresia diagnosis and outcome.

OBJECTIVES: To identify and distinguish between racial and socioeconomic disparities in age at hepatology care, diagnosis, access to surgical therapy, and liver transplant-free survival in patients with biliary atresia (BA). METHODS: Single-center retrospective cohort study of 69 BA patients from 2010 to 2021. Patients were grouped into White and non-White cohorts. The socioeconomic milieu was analyzed utilizing neighborhood deprivation index, a census tract-based calculation of six socioeconomic variables. The primary outcomes of this study were timing of the first hepatology encounter, surgical treatment with hepatic portoenterostomy (HPE), and survival with native liver (SNL) at 2 years. RESULTS: Patients were 55% male and 72% White. White patients were referred at a median of 34 days (interquartile range [IQR]: 17-65) vs. 67 days (IQR: 42-133; p = 0.001) in non-White patients. White infants were more likely to undergo HPE (42/50 patients; 84%) compared to non-White (10/19; 53%), odds ratio (OR) 4.73 (95% confidence interval: 1.46-15.31; p = 0.01). Independent of race, patients exposed to increased neighborhood-level deprivation were less likely to receive HPE (OR: 0.49, p = 0.04) and achieve SNL (OR: 0.54, p = 0.02). CONCLUSIONS: Racial and socioeconomic disparities are independently associated with timely BA diagnosis, access to surgical treatment, and transplant-free survival. Public health approaches to improve screening for pathologic jaundice in infants of diverse racial backgrounds and to test and implement interventions for socioeconomically at-risk families are needed.

Genetic analysis of Octopus cyanea reveals high gene flow in the South-West Indian Ocean.

Octopus cyanea (Gray, 1849), abundant in the South-West Indian Ocean (SWIO), constitutes a vital resource for both subsistence and commercial fisheries. However, despite this socioeconomic importance, and recent indications of overfishing, little is known about the population structure of O. cyanea in the region. To inform sustainable management strategies, this study assessed the spatio-temporal population structure and genetic variability of O. cyanea at 20 sites in the SWIO (Kenya, Tanzania, Mozambique, Madagascar, Mauritius, Rodrigues, and the Seychelle Islands) by complementary analysis of mitochondrial DNA (mtDNA) noncoding region (NCR) sequences and microsatellite markers. MtDNA analysis revealed a shallow phylogeny across the region, with demographic tests suggesting historic population fluctuations that could be linked to glacial cycles. Contrary to expectations, NCR variation was comparable to other mtDNA regions, indicating that the NCR is not a hypervariable region. Both nuclear and mtDNA marker types revealed a lack of genetic structure compatible with high gene flow throughout the region. As adults are sedentary, this gene flow likely reflects connectivity by paralarval dispersal. All samples reported heterozygote deficits, which, given the overall absence of structure, likely reflect ephemeral larval recruitment variability. Levels of mtDNA and nuclear variability were similar at all locations and congruent with those previously reported for harvested Octopodidae, implying resilience to genetic erosion by drift, providing current stock sizes are maintained. However, as O. cyanea stocks in the SWIO represent a single, highly connected population, fisheries may benefit from additional management measures, such as rotational closures aligned with paralarval ecology and spanning geopolitical boundaries.

Oral vancomycin is associated with improved inflammatory bowel disease clinical outcomes in primary sclerosing cholangitis-associated inflammatory bowel disease (PSC-IBD): A matched analysis from the Paediatric PSC Consortium.

BACKGROUND: Data on oral vancomycin for primary sclerosing cholangitis (PSC)-associated inflammatory bowel disease (IBD) are limited. AIMS: Using data from the Paediatric PSC Consortium, to examine the effect of vancomycin on IBD activity. METHODS: In this retrospective multi-centre cohort study, we matched vancomycin-treated and untreated patients (1:3) based on IBD duration at the time of primary outcome assessment. The primary outcome was Physician Global Assessment (PGA) of IBD clinical activity after 1 year (±6 months) of vancomycin. We used generalised estimating equations (GEE) to examine the association between vancomycin and PGA remission, adjusting for IBD type, severity and medication exposures. Secondary outcomes included serum labs and endoscopic remission (global rating of no activity) among those with available data and also analysed with GEE. RESULTS: 113 PSC-IBD patients received vancomycin (median age 12.7 years, 63% male). The matched cohort included 70 vancomycin-treated and 210 untreated patients. Vancomycin was associated with greater odds of IBD clinical remission (odds ratio [OR] 3.52, 95% CI 1.97-6.31; adjusted OR [aOR] 5.24, 95% CI 2.68-10.22). Benefit was maintained in sensitivity analyses restricted to non-transplanted patients and those with baseline moderate-severe PGA. Vancomycin was associated with increased odds of endoscopic remission (aOR 2.76, 95% CI 1.002-7.62; N = 101 with data), and with lower CRP (p = 0.03) and higher haemoglobin and albumin (both p < 0.01). CONCLUSION: Vancomycin was associated with greater odds of IBD clinical and endoscopic remission. Additional, preferably randomised, controlled studies are needed to characterise efficacy using objective markers of mucosal inflammation, and to examine safety and define optimal dosing.

A platform-independent AI tumor lineage and site (ATLAS) classifier.

Histopathologic diagnosis and classification of cancer plays a critical role in guiding treatment. Advances in next-generation sequencing have ushered in new complementary molecular frameworks. However, existing approaches do not independently assess both site-of-origin (e.g. prostate) and lineage (e.g. adenocarcinoma) and have minimal validation in metastatic disease, where classification is more difficult. Utilizing gradient-boosted machine learning, we developed ATLAS, a pair of separate AI Tumor Lineage and Site-of-origin models from RNA expression data on 8249 tumor samples. We assessed performance independently in 10,376 total tumor samples, including 1490 metastatic samples, achieving an accuracy of 91.4% for cancer site-of-origin and 97.1% for cancer lineage. High confidence predictions (encompassing the majority of cases) were accurate 98-99% of the time in both localized and remarkably even in metastatic samples. We also identified emergent properties of our lineage scores for tumor types on which the model was never trained (zero-shot learning). Adenocarcinoma/sarcoma lineage scores differentiated epithelioid from biphasic/sarcomatoid mesothelioma. Also, predicted lineage de-differentiation identified neuroendocrine/small cell tumors and was associated with poor outcomes across tumor types. Our platform-independent single-sample approach can be easily translated to existing RNA-seq platforms. ATLAS can complement and guide traditional histopathologic assessment in challenging situations and tumors of unknown primary.

Radiation Oncology Ransomware Attack Response Risk Analysis Using Failure Modes and Effects Analysis.

PURPOSE: There have been numerous significant ransomware attacks impacting Radiation Oncology in the past 5 years. Research into ransomware attack response in Radiation Oncology has consisted of case reports and descriptive articles and has lacked quantitative studies. The purpose of this work was to identify the significant safety risks to patients being treated with radiation therapy during a ransomware attack scenario, using Failure Modes and Effects Analysis. METHODS AND MATERIALS: A multi-institutional and multidisciplinary team conducted a Failure Modes and Effects Analysis by developing process maps and using Risk Priority Number (RPN) scores to quantify the increased likelihood of incidents in a ransomware attack scenario. The situation that was simulated was a ransomware attack that had removed the capability to access the Record and Verify (R&V) system. Five situations were considered: 1) a standard treatment of a patient with and without an R&V, 2) a standard treatment of a patient for the first fraction right after the R&V capabilities are disabled, and 3) 3 situations in which a plan modification was required. RPN scores were compared with and without R&V functionality. RESULTS: The data indicate that RPN scores increased by 71% (range, 38%-96%) when R&V functionality is disabled compared with a nonransomware attack state where R&V functionality is available. The failure modes with the highest RPN in the simulated ransomware attack state included incorrectly identifying patients on treatment, incorrectly identifying where a patient is in their course of treatment, treating the incorrect patient, and incorrectly tracking delivered fractions. CONCLUSIONS: The presented study quantifies the increased risk of incidents when treating in a ransomware attack state, identifies key failure modes that should be prioritized when preparing for a ransomware attack, and provides data that can be used to guide future ransomware resiliency research.

Virtual Access to STEM Careers: In the Field Experiments.

The Virtual Access to STEM Careers (VASC) project is an intertwined classroom and virtual reality (VR) curricular program for third through fourth graders. Elementary school students learn about and take on the roles and responsibilities of STEM occupations through authentic, problem-based tasks with physical kits and immersive VR environments. This article reports on a round of curriculum and virtual environment development and in-classroom experimentation that was guided by preliminary results gathered from our initial VASC prototyping and testing. This specific iteration focuses on curriculum for learning about sea turtles and tasks regularly completed by park rangers and marine biologists who work with these creatures and a new backend data collection component to analyze participant behavior. Our results showed that educators were able to setup and integrate VASC into their classrooms with relative ease. Elementary school students were able to learn how to interface with our system quickly and enjoyed being in the environment, making a positive link to STEM education.

Estimating the health impact of nicotine exposure by dissecting the effects of nicotine versus non-nicotine constituents of tobacco smoke: A multivariable Mendelian randomisation study.

The detrimental health effects of smoking are well-known, but the impact of regular nicotine use without exposure to the other constituents of tobacco is less clear. Given the increasing daily use of alternative nicotine delivery systems, such as e-cigarettes, it is increasingly important to understand and separate the effects of nicotine use from the impact of tobacco smoke exposure. Using a multivariable Mendelian randomisation framework, we explored the direct effects of nicotine compared with the non-nicotine constituents of tobacco smoke on health outcomes (lung cancer, chronic obstructive pulmonary disease [COPD], forced expiratory volume in one second [FEV-1], forced vital capacity [FVC], coronary heart disease [CHD], and heart rate [HR]). We used Genome-Wide Association Study (GWAS) summary statistics from Buchwald and colleagues, the GWAS and Sequencing Consortium of Alcohol and Nicotine, the International Lung Cancer Consortium, and UK Biobank. Increased nicotine metabolism increased the risk of COPD, lung cancer, and lung function in the univariable analysis. However, when accounting for smoking heaviness in the multivariable analysis, we found that increased nicotine metabolite ratio (indicative of decreased nicotine exposure per cigarette smoked) decreases heart rate (b = -0.30, 95% CI -0.50 to -0.10) and lung function (b = -33.33, 95% CI -41.76 to -24.90). There was no clear evidence of an effect on the remaining outcomes. The results suggest that these smoking-related outcomes are not due to nicotine exposure but are caused by the other components of tobacco smoke; however, there are multiple potential sources of bias, and the results should be triangulated using evidence from a range of methodologies.

Utility of Postoperative Phone Calls in Reducing Unplanned Health Care Utilization.

INTRODUCTION: Postoperative phone calls ideally proactively identify concerns. This study aimed to determine whether postoperative phone calls after elective outpatient pediatric urology surgery were associated with differences in postoperative healthcare utilization. METHODS: This retrospective cross-sectional study included patients undergoing elective outpatient pediatric urologic surgery in selected months of 2019-2021. Data were abstracted on patient demographics, postoperative call completion, number and timing of parent-initiated calls within 30 d, concerns for parent-initiated calls, and timing and indication for emergency department visits within 30 d. Patients with and without completed postoperative calls were compared. RESULTS: Of 1494 patients, 416 (38.6%) had completed postoperative phone calls; 1078 (61.4%) did not. Calls were more likely to be completed in more disadvantaged areas (Area Deprivation Index deciles 9-10; odds ratio [OR] = 3.87, 95% confidence interval [CI]: 2.70-5.54, P < 0.0001). Overall, the proportions of patients seeking emergency care within 30 d (3.6% versus 4.0%, OR = 0.90, 95% CI: 0.49-1.64, P = 0.73) and with parent-initiated phone calls (31.7% versus 31.3%, OR = 1.02, 95% CI: 0.80-1.20, P = 0.86) were similar in patients with and without postop calls completed. For children in less disadvantaged areas (Area Deprivation Index decile 1-2), the likelihood of a parent-initiated call was higher when postop calls were completed (47.8% versus 33.6%, OR = 1.79, 95% CI: 1.15-2.79, P = 0.01). CONCLUSIONS: Routine postoperative phone calls within 72 h of outpatient pediatric urologic surgery are not associated with decreased overall postoperative health care utilization, and in some cases are associated with an increase in calls to clinic. Defining patient and provider expectations for postoperative contact may make postoperative calls more useful.

Management of ectopic intestinal variceal bleeding following pancreatic transplant: Two cases.

Ectopic variceal bleeding is a potentially under recognized source of gastrointestinal (GI) hemorrhage. While vascular complications following pancreatic transplant are relatively common, the development of symptomatic ectopic venous varices has rarely been reported. We report two patients with a remote history of simultaneous kidney pancreas transplant (SPK) presenting two decades after transplant with an occult GI bleed. In both cases, a lengthy diagnostic course was required. The varices were treated with coil embolization via transhepatic approach. Our findings add to the limited literature on this topic and aid in the recognition, diagnosis, and management of this unusual presentation.

Just Get in Line: Rural-Urban Differences in Access to Pediatric Renal-Bladder Ultrasounds.

INTRODUCTION: Health-care disparities in rural and underserved areas may be exacerbated by the pandemic, personnel challenges, and supply chain limitations. This study aimed to quantify current variation in rural and urban pediatric renal ultrasound availability. METHODS: We identified all hospitals statewide and contacted radiology departments posing as a parent trying to schedule an appointment for a routine pediatric renal-bladder ultrasound. Intervals between day of contact and first available appointment were compared between rural and urban institutions. RESULTS: We were able to contact 42/48 (87.5%) rural hospitals, and 20/39 (51.3%) urban hospitals. Scheduling could not be completed in 5 rural and 7 urban hospitals. The median wait time for the 37 remaining rural and 13 remaining urban hospitals was similar: 7 (range: 0-21) days in rural hospitals and 6 (range: 0-17) days in urban hospitals (P = 0.81). If contact was made, the likelihood of scheduling within 7 d was similar in rural and urban areas (odds ratio [OR] = 0.23; 95% confidence interval [CI] 0.03-1.97; P = 0.18). However, patients were much more likely to have a completed call at a rural hospital (OR = 6.65; 95% CI: 2.3-19.2; P = 0.0005), and so in reality, patients were 2.89 times as likely to be able to schedule an renal-bladder ultrasound within 7 d at a rural compared with an urban institution (95% CI: 1.19-7.03; P = 0.019). CONCLUSIONS: While access to pediatric renal sonograms was similar within a week at rural and urban institutions once telephone contact was made, it was significantly more difficult to schedule appointments at urban institutions.

Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

New Insights on Liver-Directed Therapies in Hepatocellular Carcinoma.

The incidence of hepatocellular carcinoma (HCC) has been increasing over the past decades, but improvements in systemic and locoregional therapies is increasing survival. Current locoregional treatment options include ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and stereotactic body radiotherapy (SBRT). There is ongoing research regarding the combination of systemic and local therapies to maximize treatment effect as well as in new non-invasive, image-guided techniques such as histotripsy. There is also active research in optimizing the delivery of therapy to tumors via nanostructures and viral-vector-mediated gene therapies. In many cases, patients require a combination of therapies to achieve tumor control and prolong survival. This article provides an overview of the most common liver-directed therapies for HCC as well as insight into more recent advances in personalized medicine and emerging techniques.

Distinct effects of AMPAR subunit depletion on spatial memory.

Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3-/-) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain (Gria1/3ΔFb). In both models, loss of GluA1 and GluA3 resulted in reduced hippocampal GluA2 and increased levels of the NMDAR subunit GluN2A. Electrically-evoked AMPAR-mediated EPSPs were greatly diminished, and there was an absence of tetanus-induced LTP. Gria1/3-/- mice showed premature mortality. Gria1/3ΔFb mice were viable, and their memory performance could be analyzed. In the Morris water maze (MWM), Gria1/3ΔFb mice showed profound long-term memory deficits, in marked contrast to the normal MWM learning previously seen in single Gria1-/- and Gria3-/- knockout mice. Our results suggest a redundancy of function within the pool of available ionotropic glutamate receptors for long-term spatial memory performance.