Color (United States)

517 Background: Approximately 30% of the 18 million cancer survivors in the U.S. are working-age adults (WAA): 21 to 65 years old. Despite distinct age-related health and psychosocial needs, the characteristics of WAA survivors are unclear, and access to expert, guideline-based survivorship care remains limited. To address this gap, we created a 50-state, oncologist-led, multidisciplinary virtual cancer survivorship clinic and report our early experience. Methods: All patients enrolled in the survivorship program are assigned an oncologist-led team that includes physicians, oncology nurse navigators, a registered dietitian, genetic counselors, trained care advocates and behavioral health specialists. The survivorship care model starts with a 60-minute telehealth visit with a survivorship physician who assesses the patient and develops a personalized, guideline-based care plan. Plans address cancer screening and surveillance, management of treatment related effects, psychosocial issues and financial concerns. Recommended studies and referrals were ordered, directly arranged on the patient’s behalf and followed by the team. We conducted a retrospective review of patients who self-identified as a cancer survivor, were eligible through an employer or union benefit and completed the initial survivorship visit between January 1, 2025 and June 4, 2025 and during the pilot phase starting November 15, 2024. Results: The cohort was comprised of 185 individuals with a median age of 53 years (range 20–75); T63.8% identified as female and 74.6% white. Patients were geographically disturbed across the United States: Midwest (27.6%), Northeast (26.5%), South (30.3%), West (15.7%); 8% resided in areas of high or medium social vulnerability. Survivors represented a wide range of industries, including consumer/industrial (45.9%), technology and professional services (15.7%), finance/real estate (14.6%), non-profit/government and education sectors (13.5%), and healthcare/life sciences (10.3%). Cancer types were diverse, with non-melanocytic skin (20.5%), breast (19.5%), and melanoma (11.3%) the most common. The median age at diagnosis was 43.0 years; and 56.3% were diagnosed within the past 10 years. The survivorship team provided a wide range of services including coordinating appointments, facilitating cancer screenings, genetic counseling, directing to psychosocial support, and helping people find a facility for a specific test or support group. On average, patients interacted with care team members 13.3 times (range 1-70). Among patients who rated their experience (9 = individuals, 13 responses), the average rating was 9.9 net promoter score. Conclusions: We describe a virtual team-based survivorship care program accessible to a diverse national cohort of WAA cancer survivors. Evaluation of program outcomes, including need assessment and care gap closure, is ongoing.

Abstract As science and technology have advanced, the field of surgery is developing in the direction of “minimally invasive” and “noninvasive” procedures. Natural orifice specimen extraction surgery has emerged as a rising star in the field of minimally invasive surgery. It has increased rapidly, and it has become a hot topic inrecent years. Natural orifice specimen extraction surgery has shown advantages in alleviating postoperative pain,improving bowel movements, providing a cosmetic effect, and improving psychological state without adversely affecting cancer outcomes. This technique has been reported more in colorectal tumors, but less in laparoscopic total colectomy for refractory mixed constipation. The treatment of intractable constipation is still a difficult problem for colorectal surgeons.Jinling procedure is considered to be an ideal method. Jinling procedure with Natural orifice specimen extraction is a new surgery procedure, and intracavitary anastomosis were used which can reduce postoperative wound pain and accelerate patients' recovery.This surgical video will completely introduce the whole surgical procedure.

Sex chromosome trisomies (SCT), including XXY, XYY, and XXX syndromes, have been historically underdiagnosed. Noninvasive prenatal cell-free DNA screening has significantly increased identification of these conditions, leading to a need for pediatric care for a growing population of newborns with SCT. Our goal was to analyze and compare perinatal features, medical diagnoses, and physical features in infants with prenatal identification of SCT conditions through the first year of life. The eXtraordinarY Babies Study is an ongoing, prospective natural history study of prenatally identified children with SCT conducted by interdisciplinary teams in Colorado and Delaware. Participants were enrolled prior to 12 months of age and had pregnancy, birth, medical histories, and physical exams completed by board-certified pediatricians at 2, 6, and/or 12-month visits. Descriptive statistics were followed by comparisons between SCT groups using t-tests or ANOVA, Fisher exact, and correlations between medical features with alpha of 0.05. Relative risks were calculated compared to general population rates. 327 infants were included in the analysis (XXY=195, XXX=79, XYY=53). Major congenital anomalies were rare (1.7%). Relative risk compared to general population was elevated for breastfeeding difficulties (51.7%;RR 2.7), positional torticollis (28.2%;RR 7.2), eczema (48.0%;RR 3.5), food allergies (19.3%;RR 2.4), constipation requiring intervention (33.9%;RR 7.6), small cardiac septal defects (7.7%;RR 17.2), and structural renal abnormalities (4.4%;RR 9.7). Inpatient hospitalization was required for 12.4%, with 59.5% of hospitalizations attributable to respiratory infections. These findings of medical conditions with a higher prevalence can inform anticipatory guidance and medical management for pediatricians caring for infants with SCT. Medical findings in largest cohort of prenatally identified infants with XXY, Trisomy X, and XYY from birth to 12 months and implications for pediatric care.What's Known on This Subject: One in ∼500 individuals have an extra X or Y chromosome, or sex chromosome trisomy (SCT). Prenatal screening is now routinely identifying SCT, however there are few studies to guide perinatal and infant care for these individuals.What This Study Adds: This prospective observational study presents medical features for 327 infants with prenatally identified SCT from birth through the first year of life. Results identify where proactive screenings and/or interventions may be warranted for infants with SCT.

Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, μCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

Abstract Purpose Robotic surgery has shown promising outcomes in colorectal cancer treatment but is limited by its high cost. In response, the ArtiSential system, an articulated handheld laparoscopic instrument, has emerged as an alternative. This study aimed to assess the learning curve associated with ArtiSential during low anterior resection (LAR) of colorectal cancer. Methods A multicenter retrospective single-arm study enrolled 208 patients who underwent LAR with ArtiSential between January 2021 and October 2022. A cumulative sum (CUSUM) analysis was conducted for operation time. Three experienced surgeons, each with over 30 completed ArtiSential-assisted LAR procedures, were included in the analysis. Results The median operation time was 129 minutes; it was accompanied by minimal blood loss and no open conversions. Pathological analysis revealed favorable outcomes with high-quality total mesorectal excision and a circumferential resection margin. Surgeons A and B followed a conventional four-stage learning curve, achieving mastery after 25 and 24 cases, respectively. In contrast, Surgeon C demonstrated a unique two-stage learning curve, achieving mastery after 19 cases. Conclusion The CUSUM analysis suggests a relatively manageable learning curve, with the initial phase being completed after approximately 10 cases and proficiency attained after 20–30 cases. In conclusion, ArtiSential appears to be a promising tool for colorectal surgeons, offering a favorable learning curve and encouraging outcomes in LAR for rectal cancer.

BACKGROUND:To realize the potential of genome engineering therapeutics, tractable strategies must be identified that balance personalized therapy with the need for off-the-shelf availability. We hypothesized that regional clustering of pathogenic variants can inform the design of rational prime editing therapeutics to treat the majority of genetic cardiovascular diseases with a limited number of reagents.METHODS:We collated 2435 high-confidence pathogenic/likely pathogenic (P/LP) variants in 82 cardiovascular disease genes from ClinVar. We assessed the regional density of these variants by defining a regional clustering index. We then combined a highly active base editor with prime editing to demonstrate the feasibility of a P/LP hotspot-directed genome engineering therapeutic strategy in vitro.RESULTS:P/LP variants in cardiovascular disease genes display higher regional density than rare variants found in the general population. P/LP missense variants displayed higher average regional density than P/LP truncating variants. Following hypermutagenesis at a pathogenic hotspot, mean prime editing efficiency across introduced variants was 57±27%.CONCLUSIONS:Designing therapeutics that target pathogenic hotspots will not only address known missense P/LP variants but also novel P/LP variants identified in these hotspots as well. Moreover, the clustering of P/LP missense rather than truncating variants in these hotspots suggests that prime editing technology is particularly valuable for dominant negative disease. Although prime editing technology in relation to cardiac health continues to improve, this study presents an approach to targeting the most impactful regions of the genome for inherited cardiovascular disease.

Externalizing behaviors encompass manifestations of risk-taking, self-regulation, aggression, sensation-/reward-seeking, and impulsivity. Externalizing research often includes substance use (SU), substance use disorder (SUD), and other (non-SU/SUD) "behavioral disinhibition" (BD) traits. Genome-wide and twin research have pointed to overlapping genetic architecture within and across SUB, SUD, and BD. We created single-factor measurement models-each describing SUB, SUD, or BD traits--based on mutually exclusive sets of European ancestry genome-wide association study (GWAS) statistics exploring externalizing variables. We then applied trivariate Cholesky decomposition to these factors in order to identify BD-specific genomic variation and assess the partitioning of BD's genetic covariance with each of the other facets. Even when the residuals for indicators relating to the same substance were correlated across the SUB and SUD factors, the two factors yielded a large zero-order correlation (rg=.803). BD correlated strongly with the SUD (rg=.774) and SUB factors (rg=.778). In our initial decompositions, 33% of total BD variance remained after removing variance associated with SUD and SUB. The majority of covariance between BD and SU and between BD and SUD was shared across all factors. When only nicotine/tobacco, cannabis, and alcohol were included for the SUB/SUD factors, their zero-order correlation increased to rg=.861; in corresponding decompositions, BD-specific variance decreased to 27%. In summary, BD, SU, and SUD were highly genetically correlated at the latent factor level, and a significant minority of genomic BD variation was not shared with SU and/or SUD. Further research can better elucidate the properties of BD-specific variation by exploring its genetic/molecular correlates.

BackgroundThe Critical Assessment of Genome Interpretation (CAGI) aims to advance the state-of-the-art for computational prediction of genetic variant impact, particularly where relevant to disease. The five complete editions of the CAGI community experiment comprised 50 challenges, in which participants made blind predictions of phenotypes from genetic data, and these were evaluated by independent assessors.ResultsPerformance was particularly strong for clinical pathogenic variants, including some difficult-to-diagnose cases, and extends to interpretation of cancer-related variants. Missense variant interpretation methods were able to estimate biochemical effects with increasing accuracy. Assessment of methods for regulatory variants and complex trait disease risk was less definitive and indicates performance potentially suitable for auxiliary use in the clinic.ConclusionsResults show that while current methods are imperfect, they have major utility for research and clinical applications. Emerging methods and increasingly large, robust datasets for training and assessment promise further progress ahead.

Identifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts towards Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella . Over time on a high-fat diet, we observed differential gene expression across infection phases. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, exploring the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.