Citations

Abstract: Paradoxical embolism represents a critical and potentially fatal complication that can be associated with pulmonary embolism (PE). This case details a unique case of massive PE, further complicated by embolic stroke occurring during catheter-directed thrombolytic therapy. There was no evidence of thrombosis during the initial evaluation with lower extremity Doppler ultrasound, abdominal computed tomography scan, and transthoracic echocardiography. Differentials for the source of the emboli include unrecognized left atrial appendage thrombus, pulmonary arteriovenous malformations, and a patent left foramen ovale. Our findings highlight the complexities and treatment challenges of massive PE.

Purpose of review This review underscores the critical role and challenges associated with the widespread adoption of artificial intelligence in cancer care to enhance disease management, streamline clinical processes, optimize data retrieval of health information, and generate and synthesize evidence. Recent findings Advancements in artificial intelligence models and the development of digital biomarkers and diagnostics are applicable across the cancer continuum from early detection to survivorship care. Additionally, generative artificial intelligence has promised to streamline clinical documentation and patient communications, generate structured data for clinical trial matching, automate cancer registries, and facilitate advanced clinical decision support. Widespread adoption of artificial intelligence has been slow because of concerns about data diversity and data shift, model reliability and algorithm bias, legal oversight, and high information technology and infrastructure costs. Summary Artificial intelligence models have significant potential to transform cancer care. Efforts are underway to deploy artificial intelligence models in the cancer practice, evaluate their clinical impact, and enhance their fairness and explainability. Standardized guidelines for the ethical integration of artificial intelligence models in cancer care pathways and clinical operations are needed. Clear governance and oversight will be necessary to gain trust in artificial intelligence-assisted cancer care by clinicians, scientists, and patients.

AbstractBackgroundDisorders of gut–brain interaction (DGBI) are characterized by debilitating symptoms not explained by structural or biochemical abnormalities. While functional conditions present with complex, likely heterogeneous pathophysiology, we aimed to investigate if proxy measures of sociocultural and environmental factors are associated with the prevalence of various DGBI in populations across the world.MethodsWe performed an ecological study utilizing peer‐reviewed published datasets reporting for 26 countries prevalence rates of DGBI (Rome Foundation Global Epidemiology Study, RFGES), with six independent variables: Helicobacter pylori prevalence and household size as proxy measures for orofecal infections, gross domestic product per capita (GDP), and median age as a proxy measures for socioeconomic development, density of fast food outlets (FFO) per 100,000 population as proxy measure for processed food exposure, and suicide mortality rate per 100,000 people, and world happiness scores were used as a proxy for psychological stress. The data were retrieved from publicly accessible datasets (United Nations, CIA World Factbook, World Bank, World Happiness Report, commercial/financial reports of a global FFO chain). We used linear regression to assess variables in univariate and multivariate analysis and report standardized β coefficients with 95% confidence intervals (CI).Key ResultsThe regression model revealed that the overall prevalence of DGBI was inversely associated with both GDP per capita (β = −0.57, 95% CI: −0.92, −0.22, p = 0.002) and happiness scores (β = −0.433 95% CI: 0.821, −0.065, p = 0.023), while being positively associated with H. pylori prevalence (β = 0.40, 95% CI: 0.008, 0.81, p = 0.046). The prevalence of functional constipation (FC) was also inversely associated with GDP per capita (β = −0.50, 95% CI: −0.86, −0.13, p = 0.01) and happiness scores (β = −0.497, 95% CI: −0.863, −0.132, p = 0.01), while being positively associated with H. pylori prevalence (β = 0.53, 95% CI: 0.16, 0.91, p = 0.007). The Multivariate model analysis revealed that combining the factors of H. pylori prevalence, suicide rate, household size and happiness scores showed statistically significant association with FC (p = 0.039). Household size (β = −0.43, 95% CI: −0.82, 0.038, p = 0.033) and suicide rates (β = 0.55, 95% CI: 0.19, 0.90, p = 0.004) were statistically significantly associated with functional diarrhea. Irritable bowel syndrome (IBS) was associated with GDP per capita (β = −0.40, 95% CI: −0.79, −0.014, p = 0.043) and happiness scores (β = −0.390, 95% CI: −0.778, −0.003, p = 0.049).Conclusions & InferencesUtilizing publicly available data, the prevalence of DGBI across diverse countries is linked to various socio‐cultural and environmental factors. Collectively, the data suggests that the prevalence of DGBI is increased in less prosperous regions of the world.

Pancreatic cancer is usually detected at a late stage, when tumors have already metastasized; therefore, it has a poor prognosis with a 5-year survival rate of 11% to 12%. A key to targeting this high mortality is to develop methods for detecting the disease at a stage in which it is still local to the pancreas. However, this needs a better understanding of the events that govern pancreatic cancer oncogenesis. In this issue of Cancer Research, Neuß and colleagues report metabolic changes associated with acinar-to-ductal metaplasia (ADM), an initiating event that leads to the formation of precursor lesions for pancreatic ductal adenocarcinoma (PDAC). Their findings reveal a switch to aerobic glycolysis, increased c-MYC signaling, and increased serine metabolism as driving factors for the ADM process. These findings are important as they demonstrate that metabolic changes that drive the proliferation and metastasis of full-blown PDAC begin in the earliest lesions. The data not only provide insights into how PDAC develops but also a potential explanation for previously described findings, such as circulating lesion cells can be detected even when no carcinoma in situ is present. In summary, this article is highly relevant for furthering our understanding of how metabolic reprogramming drives the earliest events leading to PDAC development and could lay the groundwork for developing methods for early detection or intervention. See related article by Neuß et al., p. 2297

Abstract Harnessing the neuroplastic potential of the human brain is being increasingly recognized as an important neuro-oncological paradigm to facilitate safe resection of brain tumors while preserving neurological function and quality of life. Interventional neurorehabilitation, employing both invasive and noninvasive neuromodulation techniques, represents an important emerging therapeutic strategy to induce or enhance neural plasticity to promote functional recovery in brain tumor patients. This study aimed to conduct a comprehensive review of interventional neurorehabilitation techniques for glioma patients. Methods In accordance with PRISMA guidelines, searches of Medline, Embase, Web of Science, APA PsycINFO, and Cochrane were undertaken from database inception to November 28, 2023. Studies reporting on neuromodulation applied to glioma patients were included. Results Seven studies reporting findings from 118 patients met the inclusion criteria. Three neuromodulation techniques were identified and included transcranial magnetic stimulation (TMS) reported in 5 out of 7 (71.4%) studies; transcranial direct current stimulation (tDCS); and continuous cortical electrical stimulation (cCES) using grid electrodes, reported in one study each. All studies applying noninvasive stimulation to ameliorate postoperative deficits demonstrated an improvement on at least one outcome measure. The 2 studies applying tDCS and cCES to induce plasticity reported evidence of functional reorganization. Conclusions There is emerging evidence of benefits of neuromodulation to improve postoperative outcome in glioma patients. In the current literature, noninvasive stimulation has shown to have a favorable safety profile. Large-scale, double-blind, sham-controlled trials are warranted to further investigate the effectiveness of these interventions for modulating different cognitive networks in patients undergoing glioma surgery.

AbstractThere is conflicting evidence in select mouse models and humans that suggest angiotensin‐converting enzyme 2 expression is increased due to treatment with angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARBs). Given the wide range of conditions that these medications treat, further evaluation is necessary to determine safety in the context of COVID‐19. We sought to determine the association between use of ACEI/ARBs and COVID‐19 severity in patients with essential hypertension. We included 714 patients with essential hypertension diagnosed with COVID‐19 and admitted to University of Iowa Healthcare from March 1, 2020 to June 29, 2021. Severity of COVID‐19 infection was assessed based on mortality, length of stay in hospital, intensive care unit admission, and use of supplemental oxygen, invasive ventilation, and vasopressors. Multivariable logistic and linear regression analyses were used for binary and continuous outcomes, respectively. Prior exposure to ACEI/ARBs before admission was significantly associated with lower mortality (OR: 0.454, p = .015), shorter length of stay in hospital (p < .001), and decreased adjusted odds of intensive care admission (OR: 0.719; p < .042). The present results suggest that patients with essential hypertension hospitalized with COVID‐19 who had a prescription for ACEI/ARBs prior to admission exhibited less severe COVID‐19 and lower in‐hospital mortality.

ABSTRACT Introduction The Special Warfare Training Wing and Special Warfare Human Performance Support Group (HPSG; all-co-authors) were established in fiscal year (FY) 2019 to consolidate and oversee all Air Force Special Warfare (AFSPECWAR) training and provide embedded medical and human performance support to candidates with the goal of improving graduation rates and the longevity of the AFSPECWAR operator. The purpose of this manuscript is to assess the impact of the HPSG on AFSPECWAR graduation rates, musculoskeletal injury (MSKI) incidence, and cost. Materials and Methods Graduation rates, MSKI incidence (including incidence density and cumulative incidence probability), and MSKI-related health care costs were assessed across all AFSPECWAR training pipelines spanning 8 FYs 2015–22, including Indoctrination, Assessment, and Selection Courses (Selection); Tactical Air Control Party (TACP); Special Tactics (ST), and Guardian Angel (GA). Results A total of 5,728 distinct candidates were assessed over the time frame. There were significant decreases in attrition when comparing the HPSG era (FY 19–22) with the prior 4-year period for the ST (47% vs. 82% graduates) and TACP (34% vs. 41% graduates) training pipelines. The corresponding Selection (36% graduates) and GA (80% graduates) pipeline attrition rates remained stable. MSKI incidence rates (both incidence density and cumulative incidence probability) overall were not significantly different when comparing the pre-HPSG and HPSG time frames; however, they varied between the two time frames by course. GA candidates had a decrease in MSKI during the apprentice course in the HPSG era compared with the pre-HPSG era (2.4–1.0 cases per 100 trainee weeks; P &lt; .001), which corresponds to a nearly 20% reduction in the cumulative incidence probability (i.e., proportion of trainees injured) after 10 weeks of course. For ST and TACP courses, however, significantly increased incidence of MSKI was observed when comparing the two time frames (P &lt; .001), while for Selection courses, the rates remained stable. A significant reduction in the cost of MSKI-related management (62% total relative value units, 83% total costs) was observed. Conclusion The impact of the HPSG on attrition, MSKI incidence, and cost-of-care was not consistent across all training pipelines; however, taken together, there were no increases in attrition, and the cost of MSKI management was significantly lower.

Abstract Background Metformin exerts anti-inflammatory properties through a positive effect on oxidative stress, gut barrier integrity, and the gut microbiota. Our aim was to evaluate the influence of metformin on inflammatory bowel disease (IBD) outcomes in patients with type 2 diabetes mellitus (T2DM). Methods We conducted a retrospective cohort study using the TriNetX database in patients with IBD and T2DM who initiated metformin vs oral hypoglycemics or insulin (control cohort) between August 31, 2002, and August 31, 2022. One-to-one propensity score matching was performed. Primary outcomes were need for intravenous (IV) steroid use or IBD-related surgery within 1, 2, and 3 years after metformin initiation. Results Our cohorts included 1323 patients with ulcerative colitis (UC) (mean age 58.7 ± 12.2 years, 50.1% female, 77.3% White) and 1278 patients with Crohn’s disease (CD) (mean age 56.3 ± 12.6 years, 58.2% female, 76.5% White). At 1 year, patients with UC and CD were less likely to require IV steroids (UC: adjusted odds ratio [aOR], 0.45; 95% confidence interval [CI], 0.34-0.59; P &lt; .01; CD: aOR, 0.67; 95% CI, 0.53-0.85; P &lt; .01). The decreased need for IV steroids persisted in all metformin groups at 2 and 3 years. Patients with CD were at a lower risk for IBD-related surgery at year 1 (aOR, 0.5; 95% CI, 0.31-0.81; P &lt; .01), and this finding persisted at 3 years (aOR, 0.62; 95% CI, 0.43-0.89; P &lt; .01). Metformin did not affect risk for surgery in patients with UC. Conclusions Patients with IBD and T2DM on metformin had a decreased likelihood of worse IBD outcomes.

Summary Oral tolerance promotes the suppression of immune responses to innocuous antigen and is primarily mediated by regulatory T cell (Tregs). The development of oral tolerance begins in early life during a “window of tolerance,” which occurs around weaning and is mediated by components in breastmilk. Herein, we review the factors dictating this window and how Tregs are uniquely educated in early life. In early life, the translocation of luminal antigen for Treg induction is primarily dictated by goblet cell‐associated antigen passages (GAPs). GAPs in the colon are negatively regulated by maternally‐derived epidermal growth factor and the microbiota, restricting GAP formation to the “periweaning” period (postnatal day 11–21 in mice, 4–6 months in humans). The induction of solid food also promotes the diversification of the bacteria such that bacterially‐derived metabolites known to promote Tregs—short‐chain fatty acids, tryptophan metabolites, and bile acids—peak during the periweaning phase. Further, breastmilk immunoglobulins—IgA and IgG—regulate both microbial diversity and the interaction of microbes with the epithelium, further controlling which antigens are presented to T cells. Overall, these elements work in conjunction to induce a long‐lived population of Tregs, around weaning, that are crucial for maintaining homeostasis in adults.