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Genetically Modified and Gene-Edited Organisms-Objectives, Public Perception and Applications.

Genetic modification and genome editing have become important tools in agriculture, animal production, biotechnology, and human medicine, but their safety and societal acceptance remain subjects of debate. This review examines genetically modified (GM) and gene-edited organisms, distinguishing transgenesis from precision genome editing technologies, including CRISPR/Cas9, base editing, and prime editing. Representative applications in crops, livestock, pharmaceutical production, and xenotransplantation are discussed, together with their regulatory framework and public perception. Current scientific assessments indicate that approved GM foods are not inherently more hazardous to human health than their conventional counterparts when evaluated case by case. Potential benefits include improved nutritional quality, biofortification, disease resistance, increased agricultural efficiency, production of therapeutic proteins, and applications in animal health and medicine. Possible concerns include allergenicity, toxicity, unintended genetic or phenotypic effects, altered nutritional composition, environmental consequences, animal welfare issues, and uncertainties associated with long-term or large-scale deployment. Public acceptance varies substantially according to geographical region, application, cultural and ethical considerations, regulatory environment, scientific literacy, and institutional trust. Overall, GM and gene-edited organisms should not be considered a homogeneous category. Their benefits, risks, and societal acceptability depend on the specific organism, genetic modification, intended trait, and context of use, supporting a balanced, evidence-based, and case-specific approach.

acceptance

Polygenic Risk Identifies Older Adults Who May Benefit From Aspirin for the Primary Prevention of Ischemic Stroke.

BACKGROUND: Low-dose aspirin is no longer recommended for routine primary prevention in older adults due to bleeding risks outweighing vascular benefits. We hypothesized that an integrative polygenic score (iPGS) could identify a subgroup of older individuals who derive net benefit from aspirin for the primary prevention of ischemic stroke. METHODS: We performed post hoc analysis of the ASPREE randomized, placebo-controlled trial (Aspirin in Reducing Events in the Elderly) of daily 100-mg aspirin, in 12 031 genotyped participants of European ancestry aged >70 years without prior cardiovascular disease. The iPGS was derived from >1.2 million variants and evaluated both continuously and by quintiles. Cox models assessed associations between polygenic risk, ischemic stroke, and major bleeding events, and tested the interaction between the iPGS and treatment allocation, with adjustment for baseline lifestyle and clinical covariates. RESULTS: The mean age of participants was 75.1 years, and 54.9% were women. Over a median of 4.6 years, 187 ischemic strokes and 373 major bleeds occurred, including 101 intracranial bleeds (46 hemorrhagic strokes). Each 1-SD increase in the iPGS was associated with higher incident ischemic stroke risk (hazard ratio, 1.39 [95% CI, 1.20-1.62]). An interaction between the continuous iPGS and aspirin allocation was observed for ischemic stroke (P=0.04) but not major bleeding. In the highest iPGS quintile, aspirin reduced ischemic stroke by 51% (hazard ratio, 0.49 [95% CI, 0.28-0.85]) without significantly increasing major bleeding (hazard ratio, 1.15 [95% CI, 0.71-1.88]). No benefit was observed in the overall cohort or in lower-risk quintiles. CONCLUSIONS: Among older adults, high polygenic risk identifies individuals who may experience substantial stroke reduction with aspirin, with no excess bleeding. These findings raise the possibility that genomic risk stratification may enable targeted aspirin use for the primary prevention of ischemic stroke. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01038583.

Humans

Risk of Relapse and Efficacy of Adjuvant Chemotherapy in Localized Appendiceal Adenocarcinoma.

IMPORTANCE: Relapse risk and benefit of adjuvant chemotherapy after resection of appendiceal adenocarcinoma (AA) are uncertain. OBJECTIVE: To identify clinicopathologic and genomic factors associated with relapse and assess efficacy of adjuvant chemotherapy in localized AA. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study (January 2000 through February 2024; median follow-up, 62.6 months) used Kaplan-Meier and Cox proportional hazards modeling. It took place at the University of Texas MD (UT MD) Anderson Cancer Center with validation from Memorial Sloan Kettering Cancer Center (MSKCC). Participants included a complete localized cohort of 439 patients with stage I to III AA from UT MD Anderson, of whom 202 underwent surgery at UT MD Anderson and also included a validation cohort of 128 patients with stage II AA from MSKCC. EXPOSURES: Surgical resection with or without adjuvant chemotherapy. MAIN OUTCOMES AND MEASURES: Rate of recurrence, recurrence-free survival (RFS), and overall survival (OS). RESULTS: There were 439 patients with localized AA (median age, 56.5 [IQR, 22.2-83.7] years; 50% female and 50% male) managed at MD Anderson between January 2000 and February 2024. Of 202 MDA surgical patients, 19 (9.4%) had a relapse including 9 (6%) patients with stage II and 8 (19.5%) of patients stage III disease. Five-year OS was 95.7% without vs 77.2% with relapse (hazard ratio [HR], 5.50; 95% CI, 3.07-9.83; P&#x2009;<&#x2009;.001). Relative to goblet cell tumors, mucinous (HR, 5.60; 95% CI, 2.1-15; P&#x2009;<&#x2009;.001) and enteric-type (HR, 6.60; 95% CI, 2.9-15; P&#x2009;<&#x2009;.001) histologies were independently associated with relapse, as was pathologic T4 (HR, 3.30; 95% CI, 1.9-5.7; P&#x2009;<&#x2009;.001). Importantly, poor differentiation, perforation, lymphovascular invasion, and perineural invasion, known risk factors in colorectal cancer, were not significantly associated with relapse. For the complete localized cohort, adjuvant chemotherapy was not associated with improved RFS (univariate HR, 2.06; 95% CI, 1.36-3.13; P&#x2009;=&#x2009;.001 and multivariable HR, 0.98; 95% CI, 0.43-2.28; P&#x2009;=&#x2009;.90) or OS (univariate HR, 1.80; 95% CI, 1.0-3.2; P&#x2009;=&#x2009;.04 and multivariable HR, 0.71; 95% CI, 0.24-2.1; P&#x2009;=&#x2009;.53). TP53 mutation in goblet cell tumors (HR, 6.93; 95% CI, 1.50-31.00; P&#x2009;=&#x2009;.01) and GNAS mutation in nongoblet tumors (HR, 17.0; 95% CI, 3.09-93.3; P&#x2009;=&#x2009;.001) were associated with greater risk of relapse. CONCLUSIONS AND RELEVANCE: These results demonstrate that relapse after resection of localized AA is uncommon. Molecular profiling and histopathologic subtype refine risk. Adjuvant chemotherapy were not associated with benefit.

Journal Article

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-&#x3b1;, enhancing antiviral defense and exacerbating autoimmunity.

UNLABELLED: Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in IFN-&#x3b1; production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of a homologous risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent genetic IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits. HIGHLIGHTS: Genetic analysis using modern and evolutionary datasets identifies a persistent and highly prevalent lupus-associated coding haplotype in IRF7 at 11p15 The IRF7 lupus risk haplotype increases IFN-&#x3b1; production by monocytes and airway epithelial cells The IRF7 lupus risk haplotype increases IRF7 DNA binding strength and alters DNA sequence specificity A homologous lupus risk variant in mouse Irf7 enhances control of vesicular stomatitis virus and exacerbates autoantibody production.

Journal Article

Laparoscopic Surgery Is Associated With Reduced Small Bowel Obstruction Risk After Colorectal Cancer Surgery: A Nationwide Cohort Study of 5458 Patients.

INTRODUCTION: Postoperative small bowel obstruction (SBO) is a major complication following colorectal cancer surgery, yet evidence-based prevention strategies remain unclear. We aimed to clarify site-specific risk factors for SBO and evaluate the effectiveness of laparoscopic surgery and adhesion prevention materials (APMs) in preventing SBO after colorectal cancer surgery. METHODS: This retrospective cohort study analyzed 5458 patients who underwent colorectal cancer surgery at 32 Japanese institutions between 2012 and 2014. The primary endpoint was the 5-year risk of SBO. We evaluated the effects of laparoscopic surgery, APM use, and stoma creation on SBO risk. Clinical variables included demographics, tumor site, operative approach, operative details, and postoperative complications. Hospital-level clustering was addressed using mixed-effects logistic regression. RESULTS: Overall SBO incidence was 5.2% (n&#x2009;=&#x2009;283). Rectal cancer had the highest risk, whereas all colonic sites except the descending colon showed significantly lower odds. Laparoscopic surgery was associated with a 42% reduction in odds (OR 0.58; 95% CI 0.45-0.74; p&#x2009;<&#x2009;0.001), with significant reductions in ascending (NNT&#x2009;=&#x2009;22.2, p&#x2009;=&#x2009;0.001) and sigmoid colon surgery (NNT&#x2009;=&#x2009;30.2, p&#x2009;=&#x2009;0.003). APMs showed no protective effect (OR 1.01; 95% CI 0.78-1.32; p&#x2009;=&#x2009;0.94). Stoma creation significantly increased SBO risk (OR 1.84; 95% CI 1.35-2.51; p&#x2009;<&#x2009;0.001). Secondary analysis identified reoperation and postoperative ileus as additional independent risk factors. DISCUSSION: Laparoscopic surgery was associated with reduced long-term SBO risk, with significant benefits in ascending and sigmoid colon surgery. APMs showed no measurable benefit. Stoma creation increased SBO risk, with no observed difference between ileostomy and colostomy.

adhesion prevention material

Effects of Moderate-Frequency Resistance Training on Cardiometabolic Risk Factors in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis.

BACKGROUND: Resistance training (RT) effectively manages cardiometabolic risk factors in adults, but the specific effects of moderate-frequency RT (2-3 sessions/week) in adults with overweight or obesity are understudied. OBJECTIVE: This study aimed to evaluate moderate-frequency RT's effects on cardiometabolic risk factors in this population and quantify effect sizes. DATA SOURCES: PubMed, Web of Science, EMBASE, and Cochrane Library searched up to July 2025. ELIGIBILITY: English randomized controlled trials (RCTs) comparing RT (&#x2265;&#x2009;7&#x2009;weeks) to nonexercise control; nonathletic adults &#x2265;&#x2009;18&#x2009;years with BMI&#x2009;&#x2265;&#x2009;25&#x2009;kg/m2. PARTICIPANTS: 454 participants across 12 RCTs (mean age 58.93&#x2009;&#xb1;&#x2009;12.87&#x2009;years; mean BMI 31.2&#x2009;&#xb1;&#x2009;3.5&#x2009;kg/m2; ~50% female). RESULTS: RT significantly reduced diastolic blood pressure (MD&#x2009;=&#x2009;-1.53&#x2009;mmHg; 95% CI: -2.16 to -0.91; p&#x2009;<&#x2009;0.01), LDL-C (MD&#x2009;=&#x2009;-0.25&#x2009;mmol/L; 95% CI: -0.41 to -0.08; p&#x2009;<&#x2009;0.01), and triglycerides (MD&#x2009;=&#x2009;-0.17&#x2009;mmol/L; 95% CI: -0.30 to -0.04; p&#x2009;=&#x2009;0.01). No significant effects on systolic blood pressure, mean arterial pressure, waist circumference, glycemic markers, total cholesterol, or HDL-C. Subgroup analyses showed larger LDL-C/triglyceride improvements with concurrent dietary control. CONCLUSION: Moderate-frequency RT inconsistently improves cardiometabolic risk factors, benefiting diastolic blood pressure, LDL-C, and triglycerides but not glycemic or other parameters. Combining with dietary control may enhance benefits, supporting RT as a complementary strategy in multimodal lifestyle interventions. TRIAL REGISTRATION PROSPERO: CRD42022343167.

Humans

Comparative Safety of Janus Kinase Inhibitors vs Tumor Necrosis Factor Antagonists in Patients With Inflammatory Bowel Diseases.

BACKGROUND & AIMS: We conducted a retrospective cohort study comparing the safety of Janus kinase (JAK) inhibitors vs tumor necrosis factor-a (TNF) antagonists in patients with inflammatory bowel diseases (IBDs). METHODS: Using an administrative claims database, we identified patients with IBD who were new users of either JAK inhibitors or TNF antagonists between 2016 and 2023 and had insurance coverage for at least 1 year before and after treatment initiation. We compared the risk of infections (overall and serious infections requiring hospitalization), venous thromboembolism (VTE), and major adverse cardiovascular events (MACE) through stabilized inverse probability of treatment weighted Cox proportional hazards model accounting for disease characteristics, health care utilization, comorbidities, prior and concomitant medications, and competing risk of mortality. RESULTS: We included 856 patients treated with JAK inhibitors (age, 47 &#xb1; 17 years; 82% with ulcerative colitis [UC]) and 9422 patients treated with TNF antagonists (age, 45 &#xb1; 18 years; 44% with UC). JAK inhibitors were associated with higher risk of overall infections (incidence rate, 62.4 per 100 person-years [PY] vs 37.4 per 100 PY; hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.33-1.93), but not serious infections (4.9 vs 5.4; HR, 0.97; 95% CI, 0.66-1.44) compared with TNF antagonists. There was no difference in the risk of VTE (1.3 vs 1.2; HR, 0.66; 95% CI, 0.28-1.57) and MACE (0.4 vs 0.7; HR, 0.50; 95% CI, 0.19-1.30). Findings were largely stable on subgroup analyses based on type of IBD, type of JAK inhibitors, age, prior biologic exposure, concomitant use of corticosteroids, and baseline risk of adverse events. CONCLUSIONS: In an observational study of patients with IBD, JAK inhibitors were not associated with an increased risk of serious infections, VTE, or MACE compared with TNF antagonists, although the overall risk of infections was higher.

Humans

Awake Craniotomy for Eloquent Region Glioblastoma Classified by Tumor Location-A Retrospective and Prospective Cohort Study.

INTRODUCTION: The efficacy of awake craniotomy (AC) with intraoperative mapping for glioblastoma (GBM) in eloquent regions remains debated. This study aims to evaluate functional and survival outcomes of GBM patients undergoing AC stratified by tumor locations. METHODS: A combined retrospective (2015-2023, n&#x2009;=&#x2009;114: 43&#x2009;AC vs. 71 standard craniotomy) and prospective cohort (2023-2025, n&#x2009;=&#x2009;28: 13&#x2009;AC vs. 15 standard craniotomy) of GBM patients with motor/language-eloquent tumors was analyzed. Tumors were classified into motor subtypes (I: precentral gyrus; II: premotor/supplementary motor; III: internal capsule posterior limb; IV: other) and language subtypes (I: Broca's/precentral; II: postcentral/supramarginal gyrus; III: Wernicke's; IV: insular; V: other). Outcomes included extent of resection (EOR), postoperative motor/language recovery, overall survival (OS), and progression-free survival (PFS). RESULTS: The retrospective cohort demonstrated that AC has advantages in functional preservation across various motor/language subtypes. However, AC was associated with significantly deteriorated survival outcomes specifically in precentral gyrus GBMs. A prospective cohort study, enrolling only precentral gyrus GBMs for validation, yielded results consistent with the retrospective findings: worsened OS and PFS (OS: HR&#x2009;=&#x2009;3.223, p&#x2009;=&#x2009;0.0450; PFS: HR&#x2009;=&#x2009;2.374, p&#x2009;=&#x2009;0.0476); reduced EOR (AC:&#xa0;74.3%&#x2009;&#xb1;&#x2009;5.3%; standard craniotomy: 86.9%&#x2009;&#xb1;&#x2009;12.3%, p&#x2009;=&#x2009;0.0470); and better motor recovery. CONCLUSIONS: Functional preservation and survival outcomes of AC in GBM exhibited subtype-specific correlations with tumor locations. AC with intraoperative mapping effectively preserves neurological function in GBM patients. However, for tumors involving the precentral gyrus, the AC approach carries greater risks than benefits and should be considered with caution. TRIAL REGISTRATION: Strategic Intervention on Preserving Motor Function During Awake Craniotomy: NCT05143788. Strategic Intervention on Preserving Language Function During Awake Craniotomy: NCT05143775.

Adult

Sacral Neuromodulation in the Management of Refractory Pediatric Lower Urinary Tract Dysfunction.

INTRODUCTION: Sacral neuromodulation is currently used in the pediatric patient population for refractory lower urinary tract dysfunction (LUTD). Evidence, however, is currently limited for institutional experiences of long-term outcomes for sacral neuromodulation in the pediatric patient population. OBJECTIVE: The objective of this study is to perform a retrospective review of a large multi-institutional cohort of pediatric patients that underwent sacral neuromodulation (SNM) for refractory LUTD, focused on rates of symptom improvement, quality of life, and bowel-bladder dysfunction measures following device implantation. Secondary objectives included assessing device complication rates and device removals due to failure or successful resolution of symptoms. METHODS: We performed a retrospective cohort study of pediatric patients at three children's hospitals that underwent SNM device implantation for refractory LUTD. Patients 4-18 years of age who were diagnosed with refractory LUTD and managed at a participating institution with follow-up were included. Outcomes were evaluated at baseline and post-operatively after two-stage device implantation at initial follow-up and annually until device removal or final follow-up. RESULTS: From 2010 to 2022, a total of 205 children underwent SNM procedures at three pediatric hospital centers. 204 patients completed the two-stage procedure for permanent device implantation with a median follow-up of 3.4 years (1.3, 4.9). One hundred seventy-eight patients reported partial (25%) or complete (54%) device response/symptom improvement by final follow-up. Comparison of patient-reported validated questionnaires completed at baseline and by final follow-up visit revealed significant improvement in median Pediatric Quality of Life Inventory (PedsQL) (p&#x2009;=&#x2009;0.004) and Vancouver Nonneurogenic Lower Urinary Tract Dysfunction/Dysfunctional Elimination Syndrome bowel-bladder dysfunction (BBD) scores (p&#x2009;<&#x2009;0.001). Of those with any device complication (n&#x2009;=&#x2009;43;21%), 19 patients required device revision, and 20 required complete device removal. Separately, twenty-eight patients (13%) underwent device removal due to resolution of symptoms or treatment success at a median period of 5 years (4,7). CONCLUSION: SNM use demonstrated a majority of patients reporting at least partial subjective symptom improvement following device implantation across multiple institutions by final follow-up. SNM is a viable treatment option for refractory LUTD in the pediatric patient if willing to undergo an invasive procedure and in which thorough counseling of risks and benefits has occurred.

Humans

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-&#x3b1;, enhancing antiviral defense and exacerbating autoimmunity.

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-&#x3b1; production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.

ancient DNA

Temporal Patterns in the Occurrence of Principal Salmonella Serotypes for Raw Meat and Poultry Products in the United States: 1998-2024.

Microbial foodborne pathogens, such as Salmonella, have the characteristic that only some subgroups of these bacteria are highly pathogenic to humans. For the Salmonella species enterica, there are more than 2,600 serotypes. These serotypes can be host-adapted so that for any animal reservoir, such as a particular food animal species, fewer than 10 serotypes make up more than fifty percent of isolates found in the reservoir. The highly concentrated nature of serotypes within a reservoir is a key to the findings of many studies and the cornerstone of some food safety programs. Nevertheless, a key limitation is that the dominant serotypes for a reservoir are likely to change over time. This is problematic because the risk of illness associated with a reservoir can increase dramatically if a more pathogenic serotype replaces one or more less pathogenic serotypes, and vice versa. In the United States, meat and poultry have been sampled continuously by the United States Department of Agriculture Food Safety and Inspection Service (USDA FSIS) for nearly 30&#xa0;years. For this study, these data are used to describe how the occurrence of the most common serotypes for each sampled commodity has changed over time. Insight into how often and how rapidly the most common serotypes change is important for designing effective mitigation strategies. To aid the development of such a mitigation strategy, we developed a classification system to categorize serotypes based on the direction and magnitude of change in each serotype over time. This information is combined with a ranking system that describes the relative virulence of each serotype using genomic and epidemiological virulence patterns. We then developed a heuristic system to support risk management decisions regarding the potential risks and benefits of applying serotype-specific interventions.

Compositional data

Comparison of deep and nondeep hypothermia in thoracic and thoracoabdominal aortic surgery: A systematic review and meta-analysis.

OBJECTIVE: Deep hypothermic circulatory arrest (DHCA) remains a cornerstone technique for neuroprotection and end-organ preservation during ascending aorta and arch surgeries. However, its benefits and risks compared with non-DHCA strategies in thoracic and thoracoabdominal aortic aneurysm (TAAA) repair are uncertain owing to conflicting evidence and variable institutional practices. METHODS: A systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis and Cochrane guidelines. PubMed, Embase, and Cochrane Library were searched for comparative studies evaluating DHCA and non-DHCA techniques for open thoracic and TAAA repair. Random-effects models were applied to calculate pooled effect estimates. Effect sizes were risk ratio (RR) for binary end points and mean difference for continuous end points, both with 95% confidence intervals. Statistical significance was set at P < .05. Between-study heterogeneity was estimated using the I2 statistic. Metaregression analyses were used to explore the sources of heterogeneity. RESULTS: Nine observational studies, including 1041 patients, were analyzed. DHCA use was associated with a significantly lower risk of spinal cord injury (RR, 0.44; P = .012) compared with non-DHCA. However, DHCA was also associated with prolonged postoperative ventilation time (RR, 1.34; P = .003). No significant differences were observed in overall mortality, length of hospital and intensive care unit stay, stroke, or renal complications. Metaregression identified patient age as a moderator of length of stay variability, with older cohorts demonstrating longer recovery periods. CONCLUSIONS: DHCA is associated with a lower risk of spinal cord injury during TAAA repair without increasing mortality or stroke risk, although it is associated with longer ventilation times.

Humans

Five tenets for advancing evidence-based precision medicine.

Precision medicine for complex diseases uses individual-level characteristics to improve prediction of risk, therapeutic response and prognosis. Many precision medicine studies leverage existing data types and analytic methods to reveal new insights; however, beyond oncology, there has been limited success in translating precision medicine research for complex diseases into clinical practice. Thus, there is a need to identify areas for improvement, particularly in translation-oriented analytical methods and study designs. In this perspective article, we outline five fundamental tenets to enhance the efficient clinical translation of precision medicine research. These tenets focus on addressing (1) heterogeneity in risk, response and prognosis; (2) signal robustness; (3) structured statistical benchmarking against key performance indicators; (4) precision trial designs; and (5) risks and benefits to individuals and society. Our intention is to promote clinically meaningful, reproducible, scalable and equitable health outcomes through precision medicine, beyond those possible through contemporary approaches.

Precision Medicine

Prevalence and Factors Associated with Receiving a Prescription for a Direct Oral Anticoagulant Among Patients with Atrial Fibrillation on Hospice Admission.

Atrial fibrillation (AF) is prevalent in hospice care, but anticoagulation decisions in this population are not well understood. In this cross-sectional study, we described the prevalence and characteristics associated with direct oral anticoagulant (DOAC) prescription on hospice admission. We used electronic health data from adult decedents with AF in a large, for-profit hospice chain in the United States between January 1, 2017 and December 31, 2019. We used multivariable logistic regression with results reported as adjusted odds ratios (AORs) and 95% confidence intervals (CIs). Among 13,233 decedents, mean (standard deviation [SD]) age was 84.2 (9.9) years, 53.6% were female, 65.1% were White, and 56.1% were referred to hospice from a hospital. Mean (SD) CHA2DS2-VASc score were 3.8 (1.4) for males and 4.8 (1.3) for females, and mean (SD) HAS-BLED score was 2.2 (1.0). Overall, 8% of patients received a DOAC prescription on hospice admission. Characteristics associated with receiving a DOAC prescription included PPS scores of &#x2265; 20% (compared to scores < 20%), and receiving hospice care at home, nursing home, assisted living facility, or residential care home (compared to inpatient hospice). Further studies about the risks and benefits of DOAC use are needed to optimize decision-making in this population.

DOAC

Continuous Intraperitoneal Insulin Infusion for People With Type 1 Diabetes: A Literature Review and International Position Statement.

Achieving glucose targets without hypoglycaemia is the treatment goal in type 1 diabetes. Structured education, intensified insulin injection regimens, continuous glucose monitoring, automated insulin delivery, and ongoing support from a multidisciplinary team all support people with type 1 diabetes to achieve this goal. Despite these advances, significant barriers to achieving optimal management remain. Continuous intraperitoneal insulin infusion has comparable or better glucose outcomes to continuous subcutaneous insulin infusion and may reduce the frequency of hypoglycaemia, including severe episodes. Intraperitoneal insulin may be considered as a treatment modality for children and adults with type 1 diabetes using optimised intensive insulin therapy for whom subcutaneous insulin has failed due to lipoatrophy, -dystrophy or -hypertrophy, local allergy, subcutaneous insulin resistance or co-existing skin conditions. Failure of subcutaneous insulin may result in recurrent or unexplained severe hypoglycaemia or hyperglycaemia. Intraperitoneal insulin may also be considered as a treatment modality for people with type 1 diabetes with severe needle-phobia, and for those being considered for islet cell or pancreatic transplantation, or where transplantation is not available. This paper summarises current intraperitoneal insulin delivery technology, its potential risks and benefits, and an expert position statement. It is intended for use by diabetes specialist healthcare professionals, and as a reference for other healthcare professionals, commissioners, payors, people with diabetes, their carers, and advocates.

Humans

Efficacy and Safety of Rivaroxaban in Patients with Peripheral Artery Disease: A GRADE-assessed Systematic Review and Meta-Analysis.

BACKGROUND: Peripheral artery disease (PAD) is a common atherosclerotic disorder characterized by progressive arterial narrowing in the limbs. This study aims to determine the efficacy and safety of rivaroxaban, focusing on major cardiovascular events, limb outcomes, and bleeding risks. METHODS: PubMed, Cochrane, and EMBASE were searched for randomized controlled trials (RCTs) and nonrandomized comparative studies that compared rivaroxaban, either alone or in combination with aspirin, to placebo or standard care such as antiplatelet therapy. Risk ratios and hazard ratios with 95% confidence intervals were pooled using R v4.5.1 with an appropriate random-effects model applied. Subgroup analyses were performed according to rivaroxaban plus aspirin versus rivaroxaban alone. RESULTS: A total of 39,991 participants across 6 studies were included. Compared with control, use of rivaroxaban was linked to a significant reduction in composite efficacy outcomes (relative risk [RR] = 0.84, 95% confidence interval [CI] 0.78-0.91, P < 0.001), risk of acute limb ischemia (RR = 0.65, 95% CI 0.55-0.78, P < 0.001), and thromboembolism (RR = 0.60, 95% CI 0.38-0.97, P = 0.037). Although rivaroxaban plus aspirin failed to show a significant reduction in the risk of amputation, rivaroxaban alone reported a significant risk reduction (RR = 0.50, 95% CI 0.30-0.85, P = 0.003). However, its use was associated with a significantly higher risk of major bleeding (hazard ratio [HR] = 1.54, 95% CI 1.38-1.72, P < 0.001) and International Society on Thrombosis and Hemostasis-defined bleeding (RR = 1.45, 95% CI 1.19-1.76, P < 0.001). No significant differences were observed for stroke, myocardial infarction, major adverse limb events, fatal bleeding, mortality, or cardiovascular mortality. CONCLUSION: Rivaroxaban-based therapy reduced the trial-defined composite efficacy outcome, acute limb ischemia, and thromboembolism in patients with PAD, but increased the risk of major bleeding. These findings support individualized use of rivaroxaban-based therapy in carefully selected patients, balancing ischemic and limb-protective benefits against bleeding risk.

Humans

Effects of intensive blood pressure control on cardio-kidney outcomes by KDIGO risk categories: a Post Hoc analysis of ACCORD-BP and SPRINT trials.

The effects of intensive systolic blood pressure (SBP) control on cardiovascular (CV) and kidney outcomes across different Kidney Disease Improving Global Outcomes (KDIGO) risk categories remain unclear. We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) and the SPRINT-eligible Action to Control Cardiovascular Risk in Diabetes Blood Pressure (ACCORD-BP) trial. Participants were categorized into low, moderate, and high/very-high KDIGO risk groups. The primary outcomes were composite adverse CV events (defined as nonfatal myocardial infarction (MI), nonfatal stroke, fatal or hospitalized heart failure (HF), and CV mortality) and composite adverse kidney events (defined as a sustained decline in eGFR of &#x2265;&#xa0;40% and end-stage kidney disease (ESKD)). We found that intensive BP control reduced the risk of composite CV events (HR 0.68; 95% CI 0.59-0.78), with attenuated benefits in higher KDIGO risk categories (P for interaction = 0.055). This interaction was mainly driven by nonfatal MI and fatal or hospitalized HF (both P for interaction < 0.05). Intensive BP control increased the risk of composite kidney events (HR 1.88; 95% CI 1.52-2.33), mainly in low- and moderate-risk groups rather than in high/very-high risk groups (P for interaction = 0.04). Similar patterns were observed for sustained eGFR decline (P for interaction = 0.03), but not for ESKD (HR 1.05; 95% CI 0.74-1.48; P for interaction = 0.71). The KDIGO risk classification modified the effects of intensive BP control. Balancing CV benefits against potential kidney impacts in patients with different KDIGO risks during intensive BP treatment is recommended. Trial Registration: ClinicalTrials.gov Identifiers: NCT01206062 (SPRINT) and NCT00000620 (ACCORD).

Cardiovascular outcome

Molecular Residual Disease and Recurrence in Rectal Cancer Patients Undergoing Upfront Surgery: A Prospective Cohort Study.

OBJECTIVE: To evaluate the prognostic utility of postoperative circulating tumor DNA (ctDNA) for recurrence and treatment response in patients with rectal cancer undergoing upfront surgery. BACKGROUND: ctDNA-based molecular residual disease (MRD) testing shows promise in colorectal cancer, but its role in patients with rectal cancer not receiving neoadjuvant therapy is unclear. This study evaluates whether postoperative ctDNA predicts disease-free survival (DFS) and guides adjuvant chemotherapy (ACT) decisions. METHODS: We analyzed ctDNA from patients with stage II to III rectal cancer (N=250) enrolled in the GALAXY study, a multicenter registry in Japan. A clinically validated, personalized, tumor-informed 16-plex PCR next-generation sequencing assay (Signatera) was used to detect and quantify ctDNA. The primary outcome was DFS, defined as the time from landmark to recurrence, death, or the latest radiologic assessment. RESULTS: In the MRD window (2-10&#xa0;wk postsurgery, before ACT), 14.2% (35/246) of patients were ctDNA-positive and had significantly shorter DFS (HR: 9.96, 95% CI: 5.76-17.2, P <0.0001). Among patients who were ctDNA-positive in the MRD window, a significant benefit from ACT was observed (HR: 0.28, 95% CI: 0.09-0.89, P =0.031), whereas no benefit was seen in ctDNA-negative patients (HR: 0.59, 95% CI: 0.26-1.35, P =0.211). When analyzing ctDNA dynamics from the MRD window to 6 months postsurgery, recurrence risk was higher in patients who converted from ctDNA-negative to positive (HR: 8.22, 95% CI: 1.86-36.32, P =0.0055) and who remained ctDNA-positive (HR: 45.48, 95% CI: 14.31-144.57, P <0.0001) compared with serially ctDNA-negative patients. CONCLUSIONS: Postoperative ctDNA status is a robust biomarker predicting recurrence risk and ACT benefit in patients with rectal cancer undergoing upfront surgery.

Humans