Intra-abdominal temperature variation during hyperthermic intraperitoneal chemotherapy evaluated via computational fluid dynamics modeling.

Background: Hyperthermic intraperitoneal chemotherapy (HIPEC) targets intraperitoneal tumors with heated drug solutions via catheters inserted into the peritoneal space. Although studies have focused on clinical outcomes, the flow dynamics at specific intra-abdominal locations at-risk of harboring malignant cells remain poorly understood but are likely to impact the drug pharmacokinetics. Consequently, optimal protocols remain uncertain, with efficacy critically dependent on drug temperature and flow rate. This study tested the hypothesis that fluid flow dynamics at specific at-risk locations could be evaluated via a computational fluid dynamics (CFD) model of closed HIPEC in a simulated human abdominal cavity, with the goal to enable protocol optimization. Methods: A computer-aided-design (CAD) model of a human intraperitoneal cavity (30 L) was coupled with computational fluid dynamics analysis. The tested HIPEC cycle parameters included catheter position and flow rates. The cavity was subjected to forward (superior to inferior flow) or reverse flow directions at 800 or 1,120 cc/min through four catheters, two as inlets and two as outlets, placed in upper and lower abdominal positions (net fluid volume: 18.5 L). Probes to measure temperature and flow were simulated between small and large bowels, inferior to small bowel mesentery, next to duodenum, superior to liver, superior to fundus, posterior to stomach, and posterior to liver. Results: The simulations highlight heterogeneity in temperatures and flow that may occur during HIPEC at particular at-risk locations as a function of chemotherapy flow rate and direction. Temperature and fluid flow over the course of 90 min respectively varied from 0.93 K and <0.001 m/s inferior to small bowel mesentery (800 cc/min forward flow) to 3.6 K and 0.01 m/s next to the duodenum (either 800 or 1,120 cc/min forward flow). The results further suggest that monitoring outflow temperature may be inadequate for assessing HIPEC performance at at-risk locations. Conclusions: Without intra-abdominal temperature monitoring at at-risk locations, it may be unfeasible to determine whether target temperatures and temperature homogeneity are being achieved during HIPEC. This work demonstrates that computational analysis offers the capability to monitor intra-abdominal locations at-risk of suboptimal heating and fluid flow given specific HIPEC parameters, and represents a first step towards designing efficacious tumor targeting during HIPEC.

Changes in Incidence of Cirrhotic and Noncirrhotic Hepatocellular Carcinoma in the United States.

INTRODUCTION: Hepatocellular carcinoma (HCC) occurs most often in a background of cirrhosis. Patients with noncirrhotic HCC represent a distinct population, which has been characterized in single-center studies, but has not been fully evaluated on a population level in the United States. MATERIALS AND METHODS: HCC cases from Surveillance, Epidemiology, and End-Results diagnosed between 2000 and 2020 were categorized as cirrhotic or noncirrhotic. Clinical and pathologic factors, age-adjusted incidence rates (AAIR), and the overall HCC-specific survival were compared between groups. RESULTS: There were 18,592 patients with cirrhosis (80.4%) and 4545 without (19.6%). AAIRs for noncirrhotic HCC remained relatively unchanged from 2010 to 2020, with a mean incidence of 0.35 per 100,000. The AAIR for cirrhotic HCC declined from 1.59 to 0.85 per 100,000 during the same period. Patients with cirrhosis were younger (median age 62 versus 65 y, P < 0.001). Patients without cirrhosis, compared to those with cirrhosis, were less likely to have elevated alpha fetoprotein (53.9% versus 62.0%, P < 0.001), had larger tumors (median tumor size 5.0 versus 3.5 cm, P < 0.001), presented more frequently with localized disease (59.9% versus 55.8%, P < 0.001), were more likely to undergo surgery (OR 2.21, 95% CI 2.07-2.36), and had better HCC-specific survival (median 40 versus 27 mo, P < 0.001). CONCLUSIONS: The relative increase in the proportion of noncirrhotic HCC in the Untied States may be due to a decline in the incidence of cirrhotic HCC. Patients with noncirrhotic HCC have larger tumors, are more likely to undergo surgical resection, and have improved cancer-specific survival.

Evidence-Based Medicine Culture, Curriculum, and Program Outcomes: A CERA Study.

BACKGROUND: Limited faculty development is a barrier to advancing evidence-based medicine (EBM) education. This study sought to describe program director perception of EBM culture in family medicine residency training and to assess the association among structured faculty roles, EBM curricula, and specific resident outcomes including publications in EBM. METHODS: Members of the Society of Teachers of Family Medicine EBM collaborative drafted survey questions based on a literature review. The questions were electronically distributed in May 2023 to all US family medicine residency program directors who had not previously opted out by the Council of Academic Family Medicine Educational Research Alliance within its study of family medicine program directors. We analyzed results using descriptive and comparative statistics. RESULTS: The overall response rate was 44.7% (309/691). We found that 260/281 (92%) of program directors reported an EBM curriculum of some kind, and 253/281 (90%) of program directors agreed/strongly agreed that EBM was accepted by residents. Of the respondents, 72/281 (25.6%) reported that no specific faculty member was responsible for their EBM curriculum. Most program directors reported that less than 50% of residents will leave their programs with the ability to detect an error in original research (23.8%; 67/281), detect an important omission in an UpToDate article (16%; 45/281), or author a narrative review for American Family Physician (10%; 28/281). CONCLUSIONS: Program directors reported strong acceptance of EBM among residents and a high prevalence of a formal curriculum. However, many lacked a specific faculty lead, and few reported that residents had strong EBM skills. This study identified gaps in residency training to support future EBM-skilled family physicians as well as concerns about pathways for the development of future EBM faculty.

Simultaneous mapping of cathodoluminescence spectra and backscatter diffraction patterns in a scanning electron microscope.

Electron backscatter diffraction and cathodoluminescence are complementary scanning electron microscopy modes widely used in the characterisation of semiconductor films, respectively revealing the strain state of a crystalline material and the effect of this strain on the light emission from the sample. Conflicting beam, sample and detector geometries have meant it is not generally possible to acquire the two signals together during the same scan. Here, we present a method of achieving this simultaneous acquisition, by collecting the light emission through a transparent sample substrate. We apply this combination of techniques to investigate the strain field and resultant emission wavelength variation in a deep-ultraviolet micro-LED. For such compatible samples, this approach has the benefits of avoiding image alignment issues and minimising beam damage effects.

Childcare needs as a barrier to healthcare among women in a safety-net health system.

BACKGROUND: Childcare needs are an understudied social determinant of health. The effect of childcare needs on access to healthcare must be understood to inform health system interventions and policy reform. This study sought to characterize childcare needs, access to childcare, and prior experience with navigating childcare needs in healthcare settings among women in a safety-net population. METHODS: We conducted a cross-sectional study of patient-reported survey data collected in-person between April and October 2019. Surveys were administered in waiting rooms of ambulatory services in a large, urban safety-net health system in Dallas, Texas. Survey respondents were derived from a random convenience sample of women waiting for outpatient appointments. Participants were screened for having children under the age of 13 and/or childcare responsibilities for inclusion in the sample. Outcomes of interest included self-reported delayed or missed care, reasons for delayed or missed care, perceived difficulty in accessing childcare, prior methods for managing childcare during healthcare appointments, and prior experience with childcare centers. RESULTS: Among the 336 respondents (96.7% response rate), 121 (36.0%) reported delaying or missing a mean 3.7 appointments/year. Among women with delayed or missed care, 54.5% reported childcare barriers as the primary reason for deferral of care, greater than transportation (33%) or insurance (25%) barriers. Respondents rated childcare access as more difficult than healthcare access. Delayed or missed care due to childcare was more common among White (68.8%) and Black (55.0%) women compared to Hispanic women (34.3%). Common methods of navigating childcare needs during scheduled appointments included bringing children to appointments (69.1%) and re-scheduling or missing the scheduled appointment (43.0%). 40.6% of patients reported leaving an appointment before completion due to childcare needs. CONCLUSIONS: Childcare needs are a leading barrier to healthcare among women accessing care in safety-net settings. Unmet childcare needs result in deferral of care, which may impact health outcomes. Childcare access is perceived as more challenging than healthcare access itself. Health system and policy interventions are needed to address childcare as a social determinant of health.

Barriers to resection following neoadjuvant chemotherapy for resectable pancreatic adenocarcinoma: A national and local perspective.

BACKGROUND: Neoadjuvant chemotherapy (NAC) use for pancreatic ductal adenocarcinoma (PDAC) has increased, but some patients never get resection following NAC. METHODS: Data from January 2012 to December 2019 for all clinically resectable patients across two health networks were utilized, as well as data from the ACS NCDB registry. Univariate testing, multivariable logistic regression, and survival analyses were employed to evaluate failure to resection after neo-adjuvant chemotherapy. RESULTS: Of the 10 007 registry patients eligible for resection, the resected group was younger (64.6 vs. 69.5 years; p < 0.001) and had a slightly lower mean comorbidity index (0.41 vs. 0.45; p < 0.001) than the nonsurgical group. The nonsurgical group was composed of a higher percentage of Black and Hispanic patients (17.5 vs. 13.1%; p < 0.001). After adjusting for age and comorbidities, the factors associated with decreased probability of resection after NAC were evaluation at a community hospital (OR 2.4), Black or Hispanic race (OR 1.6), areas of increased high school drop-out rates (OR 1.4), and lack of private health insurance (OR 1.3). The median overall survival for nonsurgery was markedly worse than the surgical cohort (10.6 vs. 26.6 months; p < 0.001). The most frequent reasons for a lack of definitive resection were operative upstaging to unresectable (39.6%), patient preference (14.5%), progression on NAC (13.2%), deconditioning or comorbidity severity (12.5%), and nonreferral to a surgeon (8.8%). CONCLUSIONS: Racial, economic, and educational disparities have a considerable influence on the successful completion of a neoadjuvant approach for resectable PDAC. A comprehensive closed or highly collaborative/communicative multidisciplinary neoadjuvant program is optimal for treatment success and completion.

The clinical year dilemma: Examining the stressors and alternatives of pre-radiology training.

Since its reinstatement in 1997, the effectiveness of the clinical year prior to radiology residency has been a contentious topic concerning its role in cultivating skilled radiologists. This review evaluates the limitations of the one-year internship and explores alternative approaches. Utilizing databases such as PubMed, Google Scholar, and Scopus, this study identified pertinent articles that aligned with the inclusion criteria for post-graduate year 1 (PGY-1) training before radiology residency. Through a qualitative analysis of the literature, the review identifies prevalent themes concerning the drawbacks of the preliminary clinical year and potential alternative strategies. Many current trainees express skepticism about the value of the clinical year, noting a disconnect between its generalist nature and the specialized demands of subsequent radiology training. Interns felt uncertain about radiology exam indications and found radiology departments to be unapproachable, reflecting the need for alternative educational strategies to improve the preparedness and confidence of radiology interns as they transition from academic environments to clinical practice. The preparatory clinical year prior to entering radiology residency presents a mix of utility, along with alternative approaches to structuring this year. These alternatives include incorporating it into the undergraduate medical curriculum, restructuring or designing radiology-focused clinical years, and reevaluating the overall effectiveness of the clinical year in training.

Biotinylated Photocleavable Semiconductor Colloidal Quantum Dot Supraparticle Microlaser.

Luminescent supraparticles of colloidal semiconductor nanocrystals can act as microscopic lasers and are hugely attractive for biosensing, imaging, and drug delivery. However, biointerfacing these to increase functionality while retaining their main optical properties remains an unresolved challenge. Here, we propose and demonstrate red-emitting, silica-coated CdSxSe1-x/ZnS colloidal quantum dot supraparticles functionalized with a biotinylated photocleavable ligand. The success of each step of the synthesis is confirmed by scanning electron microscopy, energy dispersive X-ray and Fourier transform infrared spectroscopy, ζ-potential, and optical pumping measurements. The capture and release functionality of the supraparticle system is proven by binding to a neutravidin functionalized glass slide and subsequently cleaving off after UV-A irradiation. The biotinylated supraparticles still function as microlasers; e.g., a 9 µm diameter supraparticle has oscillating modes around 625 nm at a threshold of 58 mJ/cm2. This work is a first step toward using supraparticle lasers as enhanced labels for bionano applications.

Complete genome sequence of vaccinium-associated virus C, a new member of the family Totiviridae from Vaccinium floribundum.

Blueberries (Vaccinium sp.) are a major crop grown in the Pacific Northwest region. Currently, there are at least 17 known viruses that infect blueberry plants, and some of them cause a wide range of symptoms and economic losses. A new virus, vaccinium-associated virus C (VaVC) (family Totiviridae, genus Totivirus) was identified in an imported blueberry accession from the USDA-ARS National Clonal Germplasm Repository in Corvallis, Oregon. The complete genomic sequence of VaVC was determined, but the biological significance of VaVC is unknown and requires further study. Additional Vaccinium sp. accessions should be screened to investigate the incidence of this new virus.

Navigating the Healthcare Conundrum: Leadership Perspective from a Premier Healthcare Organization in Loma Linda's Blue Zone.

Navigating the healthcare conundrum in the Blue Zone of Loma Linda, California, requires understanding the unique factors that make this region stand out in terms of health and longevity. But more important is understanding the healthcare system sustaining the Blue Zone in Loma Linda, California. In an era marked by soaring healthcare costs and diminishing reimbursement rates, hospitals and physicians face an unprecedented challenge: providing excellent patient care while maintaining financial sustainability. This leadership perspective publication paper delves into the multifaceted struggles encountered by healthcare and hospital leaders, exploring the root causes, implications, and potential solutions for this complex issue. As we examine the evolving healthcare landscape, we aim to shed light on the critical need for innovative approaches to sustain the future of healthcare excellence in one of the five original Blue Zones.

Cyclopropenimine-Mediated CO2 Activation for the Synthesis of Polyurethanes and Small-Molecule Carbonates and Carbamates.

Carbon dioxide (CO2) is an abundant C1 feedstock with tremendous potential to produce versatile building blocks in synthetic applications. Given the adverse impact of CO2 on the atmosphere, it is of paramount importance to devise strategies for upcycling it into useful materials, such as polymers and fine chemicals. To activate such stable molecule, superbases offer viable modes of binding to CO2. In this study, a superbase cyclopropenimine derivative was found to exhibit exceptional proficiency in activating CO2 and mediating its polymerization at ambient temperature and pressure for the synthesis of polyurethanes. The versatility of this reaction can be extended to monofunctional amines and alcohols, yielding a variety of functional carbonates and carbamates.

Alcohol-alcohol cross-coupling enabled by SH2 radical sorting.

Alcohols represent a functional group class with unparalleled abundance and structural diversity. In an era of chemical synthesis that prioritizes reducing time to target and maximizing exploration of chemical space, harnessing these building blocks for carbon-carbon bond-forming reactions is a key goal in organic chemistry. In particular, leveraging a single activation mode to form a new C(sp3)-C(sp3) bond from two alcohol subunits would enable access to an extraordinary level of structural diversity. In this work, we report a nickel radical sorting-mediated cross-alcohol coupling wherein two alcohol fragments are deoxygenated and coupled in one reaction vessel, open to air.

Non-syndromic Parachute Mitral Valve "When the Valve Dives in": Case Report and Review of the Literature.

A parachute mitral valve (PMV) is a congenital mitral valve anomaly diagnosed in infancy, and it can also be discovered in adults during echocardiography. Surgical management is common in infants to prevent complications from left-heart obstructions. In adults, PMV may be found independently or with other cardiac defects. Prophylactic antibiotics are recommended for certain congenital heart anomalies before dental procedures. A study suggests reconsidering guidelines to include anomalies like bicuspid aortic valve and MVP for antibiotic prophylaxis. PMV, with transvalvular blood flow turbulence, may increase the risk of infective endocarditis, as seen in a reported case with a parachute-like mitral valve. Here, we present the case of a 62-year-old female incidentally found to have a PMV during an echocardiogram.

Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly.

BACKGROUND: Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS: SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS: Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION: Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.

Integration of Rubus yellow net virus in the raspberry genome: A story centuries in the making.

Rubus yellow net virus (RYNV) belongs to genus Badnavirus. Badnaviruses are found in plants as endogenous, inactive or activatable sequences, and/or in episomal (infectious and active) forms. To assess the state of RYNV in Rubus germplasm, we sequenced the genomes of various cultivars and mined eight raspberry whole genome datasets. Bioinformatics analysis revealed the presence of a diverse array of endogenous RYNV (endoRYNV) sequences that differ significantly in their structure; some lineages have nearly complete, yet non-functional genomes whereas others have rudimentary, short sequence fragments. We developed assays to genotype the main lineages as well as the only known episomal lineage present in the United States. This study discloses the widespread presence of endoRYNVs in commercial raspberries, likely because breeding efforts have focused on a limited pool of germplasm that harbored endoRYNVs.

Developing sarcopenia during neoadjuvant therapy is associated with worse survival in esophageal adenocarcinoma patients.

BACKGROUND: Sarcopenia in cancer patients has been associated with mixed postoperative outcomes. The aim of this study was to evaluate whether the development of sarcopenia during the neoadjuvant period is predictive of postoperative mortality in esophageal adenocarcinoma patients. METHODS: We queried a prospective database to retrieve the sarcopenic status of patients with esophageal adenocarcinoma who underwent cross-sectional imaging of the third lumbar vertebra at diagnosis and within 2 months of undergoing an esophagogastrectomy between 2014 and 2022. RESULTS: Of the 71 patients included in the study, 36 (50.7%) presented with sarcopenia at diagnosis. Of the 35 non-sarcopenic patients, 14 (40%) developed sarcopenia during the neo-adjuvant period. Patients who were not sarcopenic at diagnosis but developed sarcopenia preoperatively had significantly worse overall survival than patients sarcopenic at diagnosis and not sarcopenic preoperatively and patients experiencing no change in sarcopenic status (median 18 vs 47 vs 31 months; P = .02). Diagnostic and preoperative sarcopenic status alone were not significantly associated with overall survival (P = .48 and P = .56, respectively). Although 37 (52.1%) patients died, the cause of death was often not cancer-related (54.1%) and included acute respiratory failure, pneumonia, and cardiac arrest. No significant survival difference was observed when stratified by >10% weight loss (P = .9) or large loss in body mass index (P = .8). CONCLUSION: Developing sarcopenia during the neo-adjuvant period may be associated with worse overall survival in patients requiring esophagogastrectomy.