Citations

Abstract Aims Echo-derived left atrial (LA) stiffness index improves prognostication in patients with heart failure preserved ejection fraction but has not been studied in adults with repaired coarctation of aorta (COA). We hypothesized that, among adults with COA, those with high LA stiffness index would have worse disease severity indices [peak VO2, NT-proBNP, and right ventricular to pulmonary artery (RV-PA) coupling], heart failure hospitalization, and all-cause mortality. Methods and results LA stiffness index was estimated using the baseline echocardiogram as the quotient of septal E/e′ and LA reservoir strain (E/e′/LARS). Using the median septal LA stiffness index as the cut-off, patients were divided into high LA stiffness index (LA stiffness index >0.28) vs. low LA stiffness index groups (LA suggests index ≤0.28). The study comprised of 729 patients [age 36 ± 16 years; males 437 (60%)]. LA stiffness index correlated with RV-PA coupling (r = −0.56, P < 0.001), NT-proBNP (r = 0.62, P < 0.001), and predicted peak VO2 (r = −0.51, P < 0.001). High LA stiffness index was associated with heart failure hospitalization (adjusted HR 3.17, 95% confidence interval (CI) 1.84–7.36, P = 0.007) and all-cause mortality (adjusted HR 2.81, 95% CI 1.28–12.32, P = 0.005). LA stiffness index had superior prognostic performance for predicting 5-year risk of heart failure hospitalization (AUC 0.803, 95% CI 0.756–0.849, P < 0.001) and all-cause mortality (AUC 0.786, 95% CI 0.742–08.30, P < 0.001) compared with conventional echocardiographic indices of left heart diastolic function. Conclusion LA stiffness index improves prognostication in adults with COA and can potentially be used to guide timing of intervention or monitor response to therapy.

Abstract Objective To compare the pathology outcomes of image-guided breast biopsies across a multistate health care enterprise by the method of detection (MOD), including the positive predictive value (PPV3) and histological types. Methods Biopsies from October 31, 2017, to July 6, 2023, across 18 imaging sites in 4 states were extracted. Radiologists prospectively assigned MODs, including symptomatic presentations (self-examination, clinical examination) and imaging modalities (mammogram, tomosynthesis, US, MRI, contrast-enhanced mammogram, molecular breast imaging, other imaging). For each MOD, the rates of malignancy and cancer subtypes were calculated. Univariate and multivariate logistic regression analyses were performed. Results In 26 932 biopsies on 22 582 patients (mean age 57.6 years ± 14.2 [SD]; 22 416 women), 6068 (81.1%) cancers were detected by screening, and 1144 (15.3%) were detected by symptoms. Symptomatic presentation MODs had a higher PPV3 (43.0% vs 25.6%; P < .001), larger cancer lesion sizes (x̄ = 27.5 mm vs x̄ = 17.8 mm; P < 001), and a higher association with invasive carcinoma (96.7% vs 76.8%; P <.001) compared with screening imaging-based MODs. Methods of detection with higher PPV3s also tended to have higher rates of invasive carcinoma (Spearman’s ρ = 0.83). Conclusion Compared with breast cancers detected after symptomatic presentations, those identified via image-based screening were smaller and less often invasive, confirming the value of screening in early detection. Positive predictive value and the rate of invasive carcinoma varied in parallel across MODs.

Abstract Background Several ovarian cancer studies have suggested that a body mass index (BMI) of 30 or higher is associated with lower compliance with National Comprehensive Cancer Network–recommended chemotherapy but primarily involved treatment before 2012, when dose capping was recommended for patients with higher body surface areas. Updated analyses in the contemporary treatment era are warranted. Methods In a retrospective cohort of patients with newly diagnosed ovarian cancer receiving curative-intent carboplatin plus paclitaxel in the Yale-Smilow Cancer Network (2012-2022), we evaluated BMI at diagnosis in relation to relative dose intensity (RDI)—the ratio of completed chemotherapy dose intensity to the National Comprehensive Cancer Network–recommended dose intensity—which reflects dose modification both before and during treatment. We also assessed starting RDI (which reflects modifications before treatment) and received RDI (which reflects modifications during treatment). Data on hospitalizations and hematological chemotoxicities were collected. We examined the association between BMI (<25, 25-30, ≥30) and chemotherapy completion, hospitalizations, and toxicities using multivariable linear and logistic regressions. Results Among 327 patients, the average RDI was 79.7%, and 44.3% had an RDI below 85%. Mean (SD) starting and received RDI were 97.9% (9.1%) and 81.8% (25.7%), respectively. Higher BMI was associated with higher RDI (Paggregate = .03) and received RDI (Paggregate = .04). Body mass index was not associated with starting RDI, dose reductions, delays, hospitalizations, or hematological toxicities. Conclusions Among patients with ovarian cancer treated since 2012, the overall RDI was low. Relative dose intensity was higher among patients with a BMI of 25 or higher compared with a BMI below 25. Most dose modifications occurred during treatment and not before initiation. Studies with body composition data and interventions that maximize chemotherapy completion during treatment are warranted.

Prostate-specific antigen (PSA) screening has played a critical role in reducing prostate cancer mortality but remains controversial due to concerns regarding overdiagnosis, overtreatment, and inconsistent screening guidelines. In 2012, the United States Preventive Services Task Force (USPSTF) issued a grade D recommendation against PSA screening, leading to a national decline in PSA testing and prostate biopsy rates. This was followed by an increase in the incidence of metastatic prostate cancer at diagnosis. The USPSTF has since revised its recommendation to grade C, emphasizing shared decision-making for men aged 55 to 69 years. However, variability in screening recommendations across professional societies has resulted in clinical uncertainty, particularly for primary care physicians (PCPs), who frequently initiate PSA testing and urology referrals. This review provides an evidence-based overview of PSA screening tailored for the PCP. We performed a comprehensive literature review using Ovid MEDLINE, PubMed, Embase, and the Cochrane Library, including systematic reviews published between January 2020 and April 2025, and current guidelines from the American Urological Association (AUA), National Comprehensive Cancer Network (NCCN), European Association of Urology (EAU), and American Cancer Society (ACS). We summarize the evolving landscape of PSA screening and its integration with contemporary tools such as shared decision-making, multiparametric magnetic resonance imaging (mpMRI), and transperineally targeted biopsy. We advocate for initiating PSA screening between the ages of 45 and 49 in men with average or elevated risk, based on long-term evidence demonstrating the value of an early baseline PSA level and risk-stratified follow-up. This approach, coupled with improved diagnostic tools, can help PCPs navigate guideline variability and implement a rational, common-sense strategy to maximize early detection while minimizing harm.

Poor diet is the leading preventable risk factor for death worldwide, associated with over 10 million premature deaths and USD 8 trillion related costs every year. Artificial intelligence or AI is rapidly emerging as the most historically disruptive, innovatively dynamic, rapidly scaled, cost-efficient, and economically productive technology (which is increasingly providing transformative countermeasures to these negative health trends, especially in low- and middle-income countries (LMICs) and underserved communities which bear the greatest burden from them). Yet widespread confusion persists among healthcare systems and policymakers on how to best identify, integrate, and evolve the safe, trusted, effective, affordable, and equitable AI solutions that are right for their communities, especially in public health nutrition. We therefore provide here the first known global, comprehensive, and actionable narrative review of the state of the art of AI-accelerated nutrition assessment and healthy eating for healthcare systems, generated by the first automated end-to-end empirical index for responsible health AI readiness and maturity: the Responsible Health AI readiness and Maturity Index (RHAMI). The index is built and the analysis and review conducted by a multi-national team spanning the Global North and South, consisting of front-line clinicians, ethicists, engineers, executives, administrators, public health practitioners, and policymakers. RHAMI analysis identified the top-performing healthcare systems and their nutrition AI, along with leading use cases including multimodal edge AI nutrition assessments as ambient intelligence, the strategic scaling of practical embedded precision nutrition platforms, and sovereign swarm agentic AI social networks for sustainable healthy diets. This index-based review is meant to facilitate standardized, continuous, automated, and real-time multi-disciplinary and multi-dimensional strategic planning, implementation, and optimization of AI capabilities and functionalities worldwide, aligned with healthcare systems’ strategic objectives, practical constraints, and local cultural values. The ultimate strategic objectives of the RHAMI’s application for AI-accelerated public health nutrition are to improve population health, financial efficiency, and societal equity through the global cooperation of the public and private sectors stretching across the Global North and South.

Background/Objectives: Modeling analyses for colorectal cancer (CRC) screening focusing solely on the costs of screening do not fully capture the value of screening programs. We evaluated the clinical and economic effects of CRC stool-based screening tests, including impacts on cancer-related outcomes. Methods: A cohort-based decision-analytic cost-estimator model estimated outcomes for a single round of screening with next-generation multi-target stool DNA (ng mt-sDNA) test or fecal immunochemical test (FIT) from a US payer perspective. Undiagnosed cancers were assumed to become symptomatic (and detected) within 10 years. Clinical assumptions, advanced precancerous lesion and CRC prevalence, and test performance inputs were from clinical trial data. Adherence rates for initial screening and follow-up colonoscopy after a positive result were from real-world data. Input costs included the screening tests, follow-up colonoscopy (with and without polypectomy), and CRC treatment. Results: Compared with FIT, more individuals completed ng mt-sDNA (321,000 vs. 713,000, respectively), leading to the detection of more CRC cases (436 with FIT vs. 2235 with ng mt-sDNA), more advanced precancerous lesions, and more CRC at earlier stages. The cost of screening per patient screened was USD 801 for ng mt-sDNA and USD 124 for FIT. Follow-up colonoscopy cost was USD 149 million with ng mt-sDNA versus USD 22 million with FIT, whereas CRC treatment costs were lower for ng mt-sDNA (USD 1423 million versus USD 1474 million, respectively). When accounting for both direct and CRC averted costs, the total cost of screening and treatment was USD 1383 million with ng mt-sDNA versus USD 1427 million with FIT. Conclusions: Higher screening costs with ng mt-sDNA versus FIT are counterbalanced by savings realized from enhanced CRC prevention and earlier detection due to the superior test performance and better adherence with ng mt-sDNA.

Background/Objectives: Surveillance for anal squamous cell carcinoma (ASCC) recurrence relies on clinical examination and imaging. Post-treatment edema, fibrosis, and inflammation can result in clinically indeterminate findings (CIFs) that delay diagnosis and increase patient and system burden. Circulating tumor tissue-modified viral (TTMV)-HPV DNA offers a biologically specific, noninvasive biomarker that may clarify equivocal assessments. Methods: In this multi-center retrospective study, 233 patients with HPV-associated ASCC were evaluated, including 185 with ≥1 post-treatment TTMV-HPV DNA test. CIFs were defined as exams or imaging results not definitively positive or negative for disease, and were paired with subsequent TTMV-HPV DNA tests. Concordance was defined by prespecified follow-up windows comparing TTMV-HPV DNA results with subsequent clinical outcomes. Results: Ninety patients (39%) experienced 214 CIFs, arising from exams (46%, 98) or imaging (54%, 116). Indeterminate rates by assessment were 7% for exams, 17% for imaging, and 1.3% for TTMV-HPV DNA testing. Overall, 52 CIF/TTMV-HPV DNA pairs were eligible for analysis, and TTMV-HPV DNA resolved disease status accurately for 48/52 (92%, 95% CI: 81.5–97.9). Negative tests predicted cancer-free status for 37/41 CIFs (90%), while 100% of positive tests (11/11) were concordant with clinically confirmed recurrence. In 73% of positive cases (8/11), TTMV-HPV DNA was the first indication of recurrence (median lead-time 29 days; IQR 25–147). Conclusions: TTMV-HPV DNA testing reliably clarifies clinically indeterminate findings during ASCC surveillance, demonstrating high accuracy (92%) and earlier detection of recurrence. These data support integration into post-treatment management to reduce diagnostic uncertainty and guide timely care.

Study Design. Modified Delphi consensus process Objective. To establish a standardized, consensus-driven definition for postoperative spine infection (PSI) for research, diagnosis, and management. Summary of Background Data. Postoperative infection is a devastating and common complication following spine surgery. Rates of PSI in the literature range from 0% to over 20% depending on surgical indication and invasiveness. Despite the implications of PSI, there is no universally accepted diagnostic standard or consensus definition for infection following spine surgery, hindering research and treatment of this challenging clinical condition. Methods. A multispecialty workgroup convened by the Musculoskeletal Infection Society (MSIS) conducted a systematic literature review. Using data from the systematic review, an expert panel completed a modified Delphi process to achieve consensus. The panel included nine fellowship-trained, board-certified physicians with expertise in infectious diseases, orthopaedic and neurologic spine surgery, and musculoskeletal radiology. Iterative rounds focused on criterion selection, importance ranking, categorical grouping, and final constellation development for PSI diagnosis. Consensus was defined as a 2/3 majority, with a target of 100%. Results. The workgroup achieved 100% consensus on a new PSI definition, which incorporates six clinical domains: wound features, microbiology, imaging, inflammatory biomarkers, intraoperative findings, and histology. A single microbiological stand-alone criterion—identification of a phenotypically indistinguishable organism from two or more deep operative site specimens—was established as pathognomonic for postoperative spine infection. Additional primary and secondary supporting criteria were defined, with specific combinations required to classify cases as definite or probable PSI. Final definitions were ratified by the boards of MSIS and the European Bone & Joint Infection Society (EBJIS) Conclusion. This consensus-based definition provides a standardized framework for diagnosing postoperative spine infection, facilitating research and clinical management. The criteria balance sensitivity and specificity across diverse clinical scenarios and represent the first multispecialty, society-endorsed definition for PSI.

Background: Patients with abdominal aortic aneurysms (AAA) often have comorbidities that make them poor candidates for open surgical repair (OSR). Endovascular aortic aneurysm repair (EVAR) circumvents the morbidity associated with OSR of AAA. Candidacy for EVAR is impacted by multiple factors, including the quality and size of vascular access vessels and involvement of visceral arteries, as seen in paravisceral abdominal aortic aneurysms (PVAAA). Additional challenges, such as obesity, can complicate vascular access during EVAR. PVAAA may be better suited for fenestrated EVAR (FEVAR) using a physician-modified endograft (PMEG). Materials and Methods: In this report, we describe the case of a 64-year-old female patient with a complex PVAAA in the setting of significant aortoiliac occlusive disease (AIOD) with intermittent claudication. We describe a successful staged FEVAR technique in which vascular access challenges were first addressed by recanalization of the iliac system with femoral conduit (FC) creation, followed by successful FEVAR using bilateral FC for deployment of the PMEG. Conclusion: Patients with PAAA have unique and complex pathology that are clinically challenging to address. It is not uncommon that these patients also have co-morbid conditions that make them less-than ideal candidates for open repair. Patients may also have other conditions such as AIOD which make EVAR complex. Staged approach with iliac recanalization and femoral conduit creation followed by FEVAR with PMEG is an effective treatment option for high-risk complex patients and can help avoid common complications such as groin infection and delay in FEVAR which may result in a catastrophic event such as interval AAA rupture.

Abstract Objective Constipation is a common gastrointestinal concern in children, often prompting screening for celiac disease (CeD), particularly in refractory cases. However, limited data exist on the clinical course of constipation in children with CeD following treatment with a gluten‐free diet. Methods We reviewed electronic health records from the Mayo Clinic between 1994 and 2024 for children (<18 years) who presented with constipation and then diagnosed with CeD. Children were classified into groups based on the symptoms at the time of presentation. Constipation outcome was considered resolved by the documentation of improvement on a gluten‐free diet without ongoing laxative use, while unresolved cases required continued laxative therapy. A sub‐analysis was performed for children with encopresis. Results We identified 248 children with CeD, 177 (71%) had biopsy‐confirmed CeD, and 56 (23%) were diagnosed with serology‐only criteria. The mean age at diagnosis was 7.8 years (±4.98), with most being White (99%) and female (68%). Constipation was the main presenting symptom, but most children also exhibited additional symptoms at the time of diagnosis. Over an average of 5.3 years (±2.1) of follow‐up, constipation was resolved in 32% of children, while 68% required ongoing laxatives, in the subgroup of children with encopresis, only 29% had documented resolution. Tissue transglutaminase antibody normalization was slower in children with unresolved constipation. Trends were observed toward a higher prevalence of anxiety, depression (42% vs. 30%) and thyroid disorders (13% vs. 9%) in the unresolved group. We also noticed a trend to a higher likelihood of constipation resolution in children with type 1 diabetes mellitus (14% vs. 4%), but none reached statistical significance. Conclusion Many children with CeD continue to experience persistent unresolved constipation despite adherence to a gluten‐free diet. Comorbidities are associated with a lower rate of constipation resolution.