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BackgroundThe erosion of the early mortality advantage of elective endovascular aneurysm repair (EVAR) compared with open repair of abdominal aortic aneurysm remains without a satisfactory explanation.MethodsAn individual-patient data meta-analysis of four multicentre randomized trials of EVAR versus open repair was conducted to a prespecified analysis plan, reporting on mortality, aneurysm-related mortality and reintervention.ResultsThe analysis included 2783 patients, with 14 245 person-years of follow-up (median 5·5 years). Early (0-6 months after randomization) mortality was lower in the EVAR groups (46 of 1393 versus 73 of 1390 deaths; pooled hazard ratio 0·61, 95 per cent c.i. 0·42 to 0·89; P = 0·010), primarily because 30-day operative mortality was lower in the EVAR groups (16 deaths versus 40 for open repair; pooled odds ratio 0·40, 95 per cent c.i. 0·22 to 0·74). Later (within 3 years) the survival curves converged, remaining converged to 8 years. Beyond 3 years, aneurysm-related mortality was significantly higher in the EVAR groups (19 deaths versus 3 for open repair; pooled hazard ratio 5·16, 1·49 to 17·89; P = 0·010). Patients with moderate renal dysfunction or previous coronary artery disease had no early survival advantage under EVAR. Those with peripheral artery disease had lower mortality under open repair (39 deaths versus 62 for EVAR; P = 0·022) in the period from 6 months to 4 years after randomization.ConclusionThe early survival advantage in the EVAR group, and its subsequent erosion, were confirmed. Over 5 years, patients of marginal fitness had no early survival advantage from EVAR compared with open repair. Aneurysm-related mortality and patients with low ankle : brachial pressure index contributed to the erosion of the early survival advantage for the EVAR group. Trial registration numbers: EVAR-1, ISRCTN55703451; DREAM (Dutch Randomized Endovascular Aneurysm Management), NCT00421330; ACE (Anévrysme de l'aorte abdominale, Chirurgie versus Endoprothèse), NCT00224718; OVER (Open Versus Endovascular Repair Trial for Abdominal Aortic Aneurysms), NCT00094575.

The first centromeric protein identified in any species was CENP-A, a divergent member of the histone H3 family that was recognised by autoantibodies from patients with scleroderma-spectrum disease. It has recently been suggested to rename this protein CenH3. Here, we argue that the original name should be maintained both because it is the basis of a long established nomenclature for centromere proteins and because it avoids confusion due to the presence of canonical histone H3 at centromeres.

Tobacco use is the leading preventable cause of death in South Carolina. Smoking-related medical costs amount to $1.1 billion each year, including $393 million for Medicaid.Tobacco growing in South Carolina declined by over 50 percent from 1997 to 2008. Tobacco accounted for less than 10% of the state's cash receipts from all crops in 2007. Despite the low levels of actual tobacco growing and the small role tobacco played in the state's economy in 2008, the cultural construct of being a “tobacco growing state” continued to have a disproportionately large impact on tobacco control policy making.Between 1997 and 2008, the tobacco industry lost its alliances with the Farm Bureau Federation and Commissioners of Agriculture, former staunch industry allies, because of negotiations over the Master Settlement Agreement, the buyout of the Tobacco Price Support system, and increasing purchase of foreign tobacco.Tobacco control Policy Score rankings of 2007/2008 legislators by knowledgeable tobacco control advocates revealed that legislators from the Pee Dee region, historically the stronghold of tobacco agriculture, were similar to the rest of the state's legislators in their attitudes towards tobacco control. Tobacco area legislators were formerly strong allies of the tobacco industry and historically worked with industry lobbyists to ensure defeat or manipulation of tobacco control bills. The 2007/2008 Policy Scores indicated that this was no longer the case.Tobacco control advocates should take advantage of the growing distance between tobacco companies and its former tobacco-growing allies and the decline in the actual importance of tobacco agriculture to challenge the rhetoric and resistance to tobacco control policies in the state.The tobacco industry built significant political influence in South Carolina through lobbyists, alliances with prominent trade associations, campaign contributions and other political expenditures. From 1996 to 2006, tobacco companies, trade associations and producers contributed a total of $680,541 to candidates for state office and to political parties.There is a measurable relationship between tobacco industry contributions and legislative behavior. As rated on a Policy Score scale from 0 to 10, with 10 being extremely receptive to tobacco control and 0 being extremely pro-tobacco industry, for every $1,000 received from the tobacco industry during the 2006 election cycle, a legislator's Policy Score decreased by 1.5 points. Democrats were on average 3.6 points more favorable towards tobacco control than Republicans, after controlling for campaign contributions.South Carolina was selected by the NCI in 1990 to participate in the 17-state ASSIST program. ASSIST funded tobacco control programming within the Department of Health and Environmental Control and established the state's first formal tobacco control coalition, the Alliance for a Smoke-Free South Carolina. The Alliance disbanded in 1997, leaving tobacco control advocacy disorganized and ineffective through 2003. ASSIST ended in 1999 and was replaced by a minimally-funded DHEC Tobacco Division supported primarily by about $1 million annually from the US Centers for Disease Control and Prevention.In 1998, the state signed the Master Settlement Agreement, securing approximately $70 million per year from the major cigarette companies. In 2000, the state securitized its settlement revenue, receiving a lump sum of $900 million up front in lieu of its annual payments through 2019. Refinancing in 2008 moved this date back to 2012.The 2000 General Appropriations bill set up 4 trust funds from the securitized MSA funds, with 73% ($574 million for healthcare), including tobacco control. Only $3.34 million of the MSA revenue was spent on tobacco control between 2000 and 2008. The state allocated an additional $6 million from the General Fund to the DHEC Tobacco Division between 2002 and 2008, with no state funding for the program between 2003 and 2006 and again in 2008.The Tobacco Division developed small-scale but innovative tobacco control programming, particularly community programs to promote policy change and the Rage Against the Haze youth movement.The DHEC leadership did not prioritize tobacco control between 2000 and 2008, although its support increased gradually due to efforts by the Tobacco Division, DHEC regional staff and the voluntary health groups. Funding requests remained at $2 million, significantly below the CDC recommended $62.2 million per year. Limitations by DHEC leadership on the role that DHEC staff play in local community-wide policy change efforts changed in 2007 to allow direct participation, but remained limited in scope.The voluntary health groups failed to prioritize increased funding for the DHEC Tobacco Division relative to their other lobbying focuses and continued in 2008 to act hesitantly in their lobbying of DHEC leadership to support tobacco control funding and policy change.In 2001, tobacco control advocates formed the South Carolina Tobacco Collaborative. It received 83% of its funding from the state health department, limiting its advocacy capacity.Increased funding from voluntary health groups and national partners between 2005 and 2008 allowed the Collaborative and the other prominent tobacco control advocacy groups, the South Carolina African-American Tobacco Control Network and the Smoke-Free Action Network, to increase advocacy between 2005 and 2008. These developments led to notable successes in clean indoor air policies and attempts to increase the state's tobacco tax.The cigarette tax in South Carolina remained the lowest in the nation in 2008, at 7 cents per pack. The last cigarette tax increase was in 1977, with nearly annual attempts to increase the tax defeated by coordinated efforts from the tobacco industry. Tobacco control advocates began to push for a cigarette tax increase in 2000, without success.Between 2006 and 2008, the Collaborative developed a well-funded and well-coordinated public education and lobbying campaign to support a cigarette tax increase. In 2008, the General Assembly passed a 50-cent increase, with $5 million of the annual revenue directed to the DHEC Tobacco Division, over active opposition from the tobacco industry and its allies. Governor Mark Sanford vetoed the bill for its lack of revenue neutrality, and Speaker of the House Bobby Harrell successfully prevented a veto override in the House.The 2006-2008 cigarette tax increase campaign showed that well-funded tobacco control advocacy could be successful over tobacco industry opposition in the legislature. The defeat of the increase bill demonstrated the need for stronger grasstops lobbying and relationship building with legislative leadership.Between 1977 and 1989, local policymakers passed 19 limited clean indoor air ordinances, building momentum for consideration of a state-level clean indoor air bill. In 1990, tobacco control advocates compromised with tobacco industry lobbyists to allow the passage of a weak statewide Clean Indoor Air Act, halting significant progress on clean indoor air through 2005.In 1996, the tobacco industry succeeded in using the Synar Amendment to integrate preemption into a youth access to tobacco amendment. The tobacco industry and tobacco control advocates assumed the provision also preempted local clean indoor air activity.Beginning in 1999, local policymakers in Charleston began to support local clean indoor air ordinance attempts despite assumed preemption. While Charleston did not pass an ordinance until 2006, news coverage of the city's efforts began a wave of consideration of local ordinances, eventually supported by state and local tobacco control advocates and the Municipal Association.Between May 2006 and December 2008, 21 local clean indoor air ordinances passed, 12 of which passed before the state Supreme Court rejected the argument that preemption applied to clean indoor air ordinances. Two localities were sued over their ordinances on preemption grounds, but won both cases in the Supreme Court.During the 2007/2008 legislative session, tobacco control advocates joined together to successfully defeat multiple attempts to institute express preemption through weak clean indoor air legislation supported by the tobacco industry.Given the success of local clean indoor air efforts, the strategy of tobacco control advocates developed during 2008 should be maintained: continue to promote comprehensive local smoke-free ordinances, while avoiding any action on clean indoor air in the General Assembly.

Nitrophenols are a group of small organic molecules with significant environmental implications from the atmosphere to waterways. In this work, we investigate a series of nitrophenols and nitrophenolates, with the contrasting ortho-, meta-, and para-substituted nitro group to the phenolic hydroxy or phenolate oxygen site (2/3/4NP or NP−), implementing a suite of steady-state and time-resolved spectroscopic techniques that include UV/Visible spectroscopy, femtosecond transient absorption (fs-TA) spectroscopy with probe-dependent and global analysis, and femtosecond stimulated Raman spectroscopy (FSRS), aided by quantum calculations. The excitation-dependent (400 and 267 nm) electronic dynamics in water and methanol, for six protonated or deprotonated nitrophenol molecules (three regioisomers in each set), enable a systematic investigation of the excited-state dynamics of these functional “nanomachines” that can undergo nitro-group twisting (as a rotor), excited-state intramolecular or intermolecular proton transfer (donor–acceptor, ESIPT, or ESPT), solvation, and cooling (chromophore) events on molecular timescales. In particular, the meta-substituted compound 3NP or 3NP− exhibits the strongest charge-transfer character with FSRS signatures (e.g., C–N peak frequency), and thus, does not favor nitroaromatic twist in the excited state, while the ortho-substituted compound 2NP can undergo ESIPT in water and likely generate nitrous acid (HONO) after 267 nm excitation. The delineated mechanistic insights into the nitro-substituent-location-, protonation-, solvent-, and excitation-wavelength-dependent effects on nitrophenols, in conjunction with the ultraviolet-light-induced degradation of 2NP in water, substantiates an appealing discovery loop to characterize and engineer functional molecules for environmental applications.

Objectives:  Much attention has been paid to measuring physiological episodes of bradycardia-oxygen desaturation (BDs) in the neonatal intensive care unit (NICU). NICU patients also have spells of tachycardia-desaturation (TDs), but these have not been well-characterized. We hypothesized that TDs would be more common among infants with bronchopulmonary dysplasia (BPD). We aimed to quantify daily TDs compared to BDs in NICU patients across a range of gestational and postmenstrual ages (GA and PMA) and determine whether TDs are associated with BPD., Study Design:  We analyzed every 2-second heart rate (HR) and peripheral saturation of oxygen (SpO 2 ) throughout the NICU stay of all infants with 24 to 39 weeks GA admitted to a single, level IV NICU from 2012 to 2015. BDs were defined in our prior work (HR <100 bpm for ≥4 seconds with concurrent SpO 2 <80% for ≥10 seconds) and TDs as a 20% increase in HR from the previous 2-hour mean baseline and concurrent SpO 2 <80% for ≥10 seconds. We calculated the median daily BDs and TDs across a range of GAs and PMAs. For infants ≤32 weeks GA, we compared TDs for those with and without BPD at 36 weeks PMA and discharge on supplemental oxygen., Results:  We analyzed 782,424 hours of HR and SpO 2 data from 1,718 neonates, with a median of 271 hours analyzed per infant. TDs frequency increased with increasing PMA across all GAs. BDs occurred most frequently in infants <29 weeks GA and decreased as infants approached term equivalent age. For infants with ≤32 weeks GA, one or more TD per day from 33 to 35 weeks PMA was associated with BPD and home oxygen., Conclusion:  Episodes of TD at the thresholds defined in this analysis occurred more frequently at later PMA and were more common in infants with BPD and those requiring home oxygen., Key Points: · Desaturation episodes occur often in preterm infants.. · Bradycardia or tachycardia can coincide with desaturation.. · TD occurs later and with BPD.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective:  Hypoxemia and respiratory compromise occur in very low birth weight (VLBW, <1,500 g) infants and may be associated with shunting across patent ductus arteriosus (PDA). The impact of pharmacologic PDA treatment on acute hypoxemia and respiratory metrics is unclear. This study aimed to determine whether pharmacologic PDA treatment is associated with acute improvement in hypoxemia and respiratory metrics in VLBW infants., Study Design:  At a single center (2012-2022), all VLBW infants with echocardiographic evidence of PDA and without exclusions were classified as having received or not received pharmacologic PDA treatment (PDA-T and PDA-NT). Mean daily fraction of inspired oxygen (FIO 2 ) and Respiratory Acuity Score (RAS, PMID 30374050) were compared at baseline (day 0) and 3 days after the start of treatment. For PDA-T infants with archived 0.5 Hz (every 2-second) oxygen saturation (SpO 2 ) data, mean daily SpO 2 and the percentage of time with severe hypoxemia (SpO 2 <80%) were compared before and after treatment. Severe hypoxemia was further analyzed after stratification by clinical variables (sex, medication, gestational age, and postnatal age)., Results:  We analyzed 125 VLBW infants with PDA, of whom 66 received pharmacologic PDA treatment. We analyzed a subgroup of 43 PDA-T infants with every 2-second SpO 2 data available. PDA-T infants had higher baseline FiO 2 and RAS and lower SpO 2 than PDA-NT infants ( p  < 0.05). Compared to baseline, RAS decreased from a median of 258 (interquartile range [IQR]: 171, 348) to 254 (IQR: 174, 419), 3 days after the start of treatment ( p  = 0.012), but median FiO 2 increased from 37% (IQR: 28, 46) to 40% (IQR: 29, 52; p  = 0.008). SpO 2 and the percent time with severe hypoxemia were unchanged., Conclusion:  In this 10-year, retrospective, single-center analysis, pharmacologic PDA treatment in VLBW infants was not associated with a major improvement in acute measures of oxygenation or level of respiratory support., Key Points: · Infants with pharmacologically treated PDA had worse baseline respiratory and oxygenation metrics.. · RAS decreased but FiO2 increased 3 days after pharmacologic PDA treatment.. · Pharmacologic PDA treatment did not acutely improve SpO2 or severe hypoxemia.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Risk for colorectal cancer may accumulate through multiple environmental factors. Understanding their effects, along with genetics, age, and family history, could allow improvements in clinical decisions for screening protocols. We aimed to extend the previous work by recalibrating an environmental risk score (e-Score) for colorectal cancer among a sample of US veteran participants of the Million Veteran Program., Methods: Demographic, lifestyle, and colorectal cancer data from 2011 to 2022 were abstracted from survey responses and health records of 227,504 male Million Veteran Program participants. Weighting for each environmental factor's effect size was recalculated using Veterans Affairs training data to create a recalibrated e-Score. This recalibrated score was compared with the original weighted e-Score in a validation sample of 113,752 (n cases = 590). Nested multiple logistic regression models tested associations between quintiles for recalibrated and original e-Scores. Likelihood ratio tests were used to compare model performance., Results: Age (P < 0.0001), education (P < 0.0001), diabetes (P < 0.0001), physical activity (P < 0.0001), smoking (P < 0.0001), NSAID use (P < 0.0001), calcium (P = 0.015), folate (P = 0.020), and fruit consumption (P = 0.019) were significantly different between colorectal cancer case and control groups. In the validation sample, the recalibrated e-Score model significantly improved the base model performance (P < 0.001), but the original e-Score model did not (P = 0.07). The recalibrated e-Score model quintile 5 was associated with significantly higher odds for colorectal cancer compared with quintile 1 (Q5 vs. Q1: 1.79; 95% CI, 1.38-2.33)., Conclusions: Multiple environmental factors and the recalibrated e-Score quintiles were significantly associated with colorectal cancer cases., Impact: A recalibrated, veteran-specific e-Score could be used to help personalize colorectal cancer screening and prevention strategies., (©2024 The Authors; Published by the American Association for Cancer Research.)

Objective: To evaluate cardiorespiratory status in preterm infants receiving dexmedetomidine using high-resolution physiologic data., Study Design: We analyzed preterm infants with continuous heart rate (HR) and oxygen saturation (SpO2) data for 24 hours preceding and 48 hours following dexmedetomidine initiation. Invasive arterial blood pressure (ABP), when available, was analyzed., Results: In 100 infants with mean gestational age of 28 weeks and high baseline illness severity, mean HR decreased from 152 to 141 beats per minute while mean SpO2 increased from 91% to 93% in the 48 hours after dexmedetomidine initiation (p<0.01). In 57 infants with continuous ABP monitoring, mean ABP increased from 40 to 42 mmHg (p=0.01). Vasoactive-inotropic support increased before and after initiation., Conclusions: We observed cardiorespiratory changes in critically ill preterm infants following dexmedetomidine initiation; mean HR decreased and mean SpO2 increased in the 48 hours after initiation. In a subset, mean ABP increased along with vasoactive-inotropic support., Competing Interests: Dr. Vesoulis receives research funding and personal fees from Medtronic PLC outside the submitted work. All other authors have no financial conflicts of interest. No outside entities played a role in the design, analysis, writing, or decision to publish., (Thieme. All rights reserved.)

Background: A pulse oximetry warning system (POWS) to analyze heart rate and oxygen saturation data and predict risk of sepsis was developed for very low birth weight (VLBW) infants., Methods: We determined the clinical correlates and positive predictive value (PPV) of a high POWS score in VLBW infants. In a two-NICU retrospective study, we identified times when POWS increased above 6 (POWS spike). We selected an equal number of control times, matched for gestational and chronologic age. We reviewed records for infection and non-infection events around POWS spikes and control times. We calculated the frequencies and PPV of a POWS spike for infection or another significant event., Results: We reviewed 111 POWS spike times and 111 control times. Days near POWS spikes were more likely to have clinical events than control days (77% vs 50%). A POWS spike had 52% PPV for suspected or confirmed infection and 77% for any clinically significant event. Respiratory deterioration occurred near more POWS spike times than control times (34% vs 18%)., Conclusions: In a retrospective cohort, infection and respiratory deterioration were common clinical correlations of a POWS spike. POWS had a high PPV for significant clinical events with or without infection., Impact: There are significant gaps in understanding the best approach to implementing continuous sepsis prediction models so that clinicians can best respond to early signals of deterioration. Infection and respiratory deterioration were common clinical events identified at the time of a high predictive model score. Understanding the clinical correlates of a high-risk early warning score will inform future implementation efforts., (© 2024. The Author(s).)

Objective:  Gastroschisis is the most common congenital abdominal wall defect, with an increasing incidence. It results in extrusion of abdominal contents with associated delayed intestinal motility. Abnormal heart rate characteristics (HRCs) such as decreased variability occur due to the inflammatory response to sepsis in preterm infants. This study aimed to test the hypothesis that infants with gastroschisis have decreased heart rate variability (HRV) after birth and that this physiomarker may predict outcomes., Study Design:  We analyzed heart rate data from and clinical variables for all infants admitted with gastroschisis from 2009 to 2020., Results:  Forty-seven infants were admitted during the study period and had available data. Complex gastroschisis infants had reduced HRV after birth. For those with sepsis and necrotizing enterocolitis, abnormal HRCs occurred early in the course of illness., Conclusion:  Decreased HRV was associated with complex gastroschisis. Infants in this group experienced complications that prolonged time to full enteral feeding and time on total parenteral nutrition., Key Points: · Infants with gastroschisis can be classified into two subcategories, simple and complex disease.. · Those with complex disease often require prolonged stays in the neonatal intensive care unit and costly hospitalizations. We hypothesized that infants with complex gastroschisis are more likely to have abnormal HRC due to intestinal inflammation.. · In this study, we identified associations between abnormal HRV, heart rate characteristicHRC, and the development of gastroschisis complications. Additionally, we described differences in clinical characteristics between infants with complex versus simple gastroschisis.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: We assessed the real-world performance of stool-based tests (SBTs) for colorectal cancer screening., Materials and Methods: Retrospective review of average-risk individuals with positive SBT for advanced neoplasia (adenocarcinoma, advanced adenoma, and/or advanced serrated lesions) detection at follow-up colonoscopy., Results: There was no statistical difference in the detection of advanced neoplasia (P= 0.16) between SBTs [30.7% for multitargeted stool DNA (mt-sDNA) vs 22.8% for fecal immunochemical test]. However, there was a significant difference in the detection of advanced serrated lesions (11.3% for mt-sDNA vs 1.8% for fecal immunochemical test, P< 0.001)., Conclusion: There was no difference between SBTs for advanced neoplasia detection, though mt-sDNA detected significantly more advanced serrated lesions., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The objective of this study was to examine the association of cardiorespiratory events, including apnea, periodic breathing, intermittent hypoxemia (IH), and bradycardia, with late-onset sepsis for extremely preterm infants (<29 weeks of gestational age) on vs off invasive mechanical ventilation., Study Design: This is a retrospective analysis of data from infants enrolled in Pre-Vent (ClinicalTrials.gov identifier NCT03174301), an observational study in 5 level IV neonatal intensive care units. Clinical data were analyzed for 737 infants (mean gestational age: 26.4 weeks, SD 1.71). Monitoring data were available and analyzed for 719 infants (47 512 patient-days); of whom, 109 had 123 sepsis events. Using continuous monitoring data, we quantified apnea, periodic breathing, bradycardia, and IH. We analyzed the relationships between these daily measures and late-onset sepsis (positive blood culture >72 hours after birth and ≥5-day antibiotics)., Results: For infants not on a ventilator, apnea, periodic breathing, and bradycardia increased before sepsis diagnosis. During times on a ventilator, increased sepsis risk was associated with longer events with oxygen saturation <80% (IH80) and more bradycardia events before sepsis. IH events were associated with higher sepsis risk but did not dynamically increase before sepsis, regardless of ventilator status. A multivariable model including postmenstrual age, cardiorespiratory variables (apnea, periodic breathing, IH80, and bradycardia), and ventilator status predicted sepsis with an area under the receiver operator characteristic curve of 0.783., Conclusion: We identified cardiorespiratory signatures of late-onset sepsis. Longer IH events were associated with increased sepsis risk but did not change temporally near diagnosis. Increases in bradycardia, apnea, and periodic breathing preceded the clinical diagnosis of sepsis., Competing Interests: Declaration of Competing Interest Some authors have financial conflicts of interest. JRM and DEL own stock in Medical Prediction Sciences Corporation. JRM is a consultant for Nihon Kohden Digital Health Solutions, proceeds donated to the University of Virginia. ZAV is a consultant for Medtronic. All other authors have no financial conflicts to disclose. No authors have any nonfinancial conflicts of interest to disclose. Funding Support: We acknowledge the following NIH grants for funding the work presented in this manuscript. University of Virginia (NCT03174301): U01 HL133708, K23 HD097254, HL133708-05S1. Case Western Reserve University: U01 HL133643. Northwestern University: U01 HL133704. University of Alabama at Birmingham: U01 HL133536, K23 HL157618. University of Miami: U01 HL133689. Washington University: U01 HL133700, F., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Localized delivery of angiogenesis-promoting factors such as small molecules, nucleic acids, peptides, and proteins to promote the repair and regeneration of damaged tissues remains a challenge in vascular tissue engineering. Current delivery methods such as direct administration of therapeutics can fail to maintain the necessary sustained release profile and often rely on supraphysiologic doses to achieve the desired therapeutic effect. By implementing a microparticle delivery system, localized delivery can be coupled with sustained and controlled release to mitigate the risks involved with the high dosages currently required from direct therapeutic administration., Methods: For this purpose, poly(lactic-co-glycolic acid) (PLGA) microparticles were fabricated via anti-solvent microencapsulation and the loading, release, and delivery of model angiogenic molecules, specifically a small molecule, nucleic acid, and protein, were assessed in vitro using microvascular fragments (MVFs)., Results: The microencapsulation approach utilized enabled rapid spherical particle formation and encapsulation of model drugs of different sizes, all in one method. The addition of a fibrin scaffold, required for the culture of the MVFs, reduced the initial burst of model drugs observed in release profiles from PLGA alone. Lastly, in vitro studies using MVFs demonstrated that higher concentrations of microparticles led to greater co-localization of the model therapeutic (miRNA) with MVFs, which is vital for targeted delivery methods. It was also found that the biodistribution of miRNA using the delivered microparticle system was enhanced compared to direct administration., Conclusion: Overall, PLGA microparticles, formulated and loaded with model therapeutic compounds in one step, resulted in improved biodistribution in a model of the vasculature leading to a future in translational revascularization., (© 2024 S. Karger AG, Basel.)

Background: Comprehensive adverse event (AE) surveillance programs in interventional radiology (IR) are rare. Our aim was to develop and validate a retrospective electronic surveillance model to identify outpatient IR procedures that are likely to have an AE, to support patient safety and quality improvement., Methods: We identified outpatient IR procedures performed in the period from October 2017 to September 2019 from the Veterans Health Administration (n = 135,283) and applied electronic triggers based on posyprocedure care to flag cases with a potential AE. From the trigger-flagged cases, we randomly sampled n = 1,500 for chart review to identify AEs. We also randomly sampled n = 600 from the unflagged cases. Chart-reviewed cases were merged with patient, procedure, and facility factors to estimate a mixed-effects logistic regression model designed to predict whether an AE occurred. Using model fit and criterion validity, we determined the best predicted probability threshold to identify cases with a likely AE. We reviewed a random sample of 200 cases above the threshold and 100 cases from below the threshold from October 2019 to March 2020 (n = 20,849) for model validation., Results: In our development sample of mostly trigger-flagged cases, 444 of 2,096 cases (21.8%) had an AE. The optimal predicted probability threshold for a likely AE from our surveillance model was >50%, with positive predictive value of 68.9%, sensitivity of 38.3%, and specificity of 95.3%. In validation, chart-reviewed cases with AE probability >50% had a positive predictive value of 63% (n = 203). For the period from October 2017 to March 2020, the model identified approximately 70 IR cases per month that were likely to have an AE., Conclusions: This electronic trigger-based approach to AE surveillance could be used for patient-safety reporting and quality review., (Copyright © 2024. Published by Elsevier Inc.)

One goal of colorectal cancer (CRC) screening is to prevent CRC incidence by removing precancerous colonic polyps, which are detected in up to 50% of screening examinations. Yet, the lifetime risk of CRC is 3.9%-4.3%, so it is clear that most of these individuals with polyps would not develop CRC in their lifetime. It is, therefore, a challenge to determine which individuals with polyps will benefit from follow-up, and at what intervals. There is some evidence that individuals with advanced polyps, based on size and histology, benefit from intensive surveillance. However, a large proportion of individuals will have small polyps without advanced histologic features (ie, "nonadvanced"), where the benefits of surveillance are uncertain and controversial. Demand for surveillance will further increase as more polyps are detected due to increased screening uptake, recent United States recommendations to expand screening to younger individuals, and emergence of polyp detection technology. We review the current understanding and clinical implications of the natural history, biology, and outcomes associated with various categories of colon polyps based on size, histology, and number. Our aims are to highlight key knowledge gaps, specifically focusing on certain categories of polyps that may not be associated with future CRC risk, and to provide insights to inform research priorities and potential management strategies. Optimization of CRC prevention programs based on updated knowledge about the future risks associated with various colon polyps is essential to ensure cost-effective screening and surveillance, wise use of resources, and inform efforts to personalize recommendations., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: A heart rate characteristics index (HeRO score), incorporating low variability and superimposed decelerations, was developed as a sepsis risk indicator for preterm infants in the neonatal intensive care unit (NICU). A rise in the risk score should prompt consideration of other clinical changes that may be signs of sepsis to decide whether a workup and antibiotics are needed. We aimed to develop a framework to systematically consider signs potentially indicating sepsis in very low birth weight (VLBW) infants., Study Design: We developed easy-recall acronyms for 10 signs of sepsis in VLBW infants. Over 12 months in a level IV NICU, neonatology fellows completed a brief survey after each shift to document changes prompting sepsis workups. We analyzed associations between survey data, hourly heart rate characteristic data, and the diagnosis of the workup, grouped as culture-positive sepsis (CXSEP, positive blood or urine culture), clinical sepsis (CLINSEP, negative cultures treated with antibiotics ≥5 days), or sepsis ruled out (SRO, negative cultures and <3 days antibiotics)., Results: We analyzed 93 sepsis workups in 48 VLBW infants (35 CXSEP, 20 CLINSEP, and 38 SRO). The most frequently cited changes prompting the workups were heart rate patterns and respiratory deterioration, which were common in all three categories. Low blood pressure and poor perfusion were uncommonly cited but were more likely to be associated with CXSEP than the other signs. A rise in the HeRO score ≥1 from 0 to 12 hours before compared with 12to 72 hours prior the blood culture occurred in 31% of workups diagnosed as CXSEP, 16% CLINSEP, and 31% SRO., Conclusion: The HeRO score can alert clinicians to VLBW infants at high or increasing risk of a sepsis-like illness, but heart rate characteristic patterns are highly variable in individual babies. The easy-recall NeoSEP-10 framework can assist clinicians in considering other clinical changes when making decisions about sepsis workups and the duration of antibiotics., Key Points: · Abnormal heart rate characteristics can indicate sepsis or other pathologies in preterm infants.. · We developed a simple bedside tool to consider clinical signs potentially associated with sepsis.. · Considering vital sign trends together with clinical changes is a key to right-timing antibiotics.., Competing Interests: None declared., (Thieme. All rights reserved.)

Adeno-associated virus (AAV) vector gene therapy is a promising approach to treat rare genetic diseases; however, an ongoing challenge is how to best modulate host immunity to improve transduction efficiency and therapeutic outcomes. This report presents two studies characterizing multiple prophylactic immunosuppression regimens in male cynomolgus macaques receiving an AAVrh10 gene therapy vector expressing human coagulation factor VIII (hFVIII). In study 1, no immunosuppression was compared with prednisolone, rapamycin (or sirolimus), rapamycin and cyclosporin A in combination, and cyclosporin A and azathioprine in combination. Prednisolone alone demonstrated higher mean peripheral blood hFVIII expression; however, this was not sustained upon taper. Anti-capsid and anti-hFVIII antibody responses were robust, and vector genomes and transgene mRNA levels were similar to no immunosuppression at necropsy. Study 2 compared no immunosuppression with prednisolone alone or in combination with rapamycin or methotrexate. The prednisolone/rapamycin group demonstrated an increase in mean hFVIII expression and a mean delay in anti-capsid IgG development until after rapamycin taper. Additionally, a significant reduction in the plasma cell gene signature was observed with prednisolone/rapamycin, suggesting that rapamycin's tolerogenic effects may include plasma cell differentiation blockade. Immunosuppression with prednisolone and rapamycin in combination could improve therapeutic outcomes in AAV vector gene therapy., (© 2023. The Author(s).)

Objective: Real-world data is crucial to inform existing opportunistic colorectal cancer (CRC) prevention programs. This study aimed to assess CRC screening adherence and utilization of various screening modalities within a Primary Care network over a three-year period (2017-2019)., Methods: A retrospective review of individuals aged 50-75 years at average CRC risk, with at least one clinic visit in the previous 24 months. The primary outcome, CRC screening adherence (overall and by modality) was examined among the entire eligible population and newly adherent individuals each calendar year. The final sample included 107,366 patients and 218,878 records., Results: Overall CRC screening adherence increased from 71% in 2017 to 78% in 2019. For "up-to-date" individuals, colonoscopy was the predominant modality (accounting for approximately 74%, versus 4% of adherence for non-invasive options). However, modality utilization trends changed over time in these individuals: mt-sDNA increased 10.2-fold, followed by FIT (1.6-fold) and colonoscopy (1.1-fold). Among newly adherent individuals, the proportion screened by colonoscopy and FOBT decreased over time (89% to 80% and 2.4% to 1.2%, respectively), while uptake of FIT and mt-sDNA increased (7.7% to 11.5% and 0.9% to 6.8%, respectively). Notably, FIT and mt-sDNA increases were most evident in age and race-ethnicity groups with the lowest screening rates., Conclusions: In an opportunistic CRC screening program, adherence increased but remained below the national 80% goal. While colonoscopy remained the most utilized modality, new colonoscopy uptake declined, compared with rising mt-sDNA and FIT utilization. Among minority populations, new uptake increased most with mt-sDNA and FIT.

Background: Early diagnosis of late-onset sepsis (LOS) and necrotizing enterocolitis (NEC) in very low birth weight (VLBW, <1,500 g) infants is challenging due to non-specific clinical signs. Inflammatory biomarkers increase in response to infection, but non-infectious conditions also cause inflammation. Cardiorespiratory data contain physiological biomarkers, or physiomarkers, of sepsis that may be useful in combination with inflammatory hematologic biomarkers for sepsis diagnosis., Objectives: To determine whether inflammatory biomarkers measured at the time of LOS or NEC diagnosis differ from times without infection and whether biomarkers correlate with cardiorespiratory sepsis physiomarkers in VLBW infants., Methods: Remnant plasma sample collection from VLBW infants occurred with blood draws for routine laboratory testing and suspected sepsis. We analyzed 11 inflammatory biomarkers and a pulse oximetry sepsis warning score (POWS). We compared biomarker levels obtained at the time of gram-negative (GN) bacteremia or NEC, gram-positive (GP) bacteremia, negative blood cultures, and no suspected infection., Results: We analyzed 188 samples in 54 VLBW infants. Several biomarkers were increased at the time of GN LOS or NEC diagnosis compared with all other samples. POWS was higher in patients with LOS and correlated with five biomarkers. IL-6 had 78% specificity at 100% sensitivity to detect GN LOS or NEC and added information to POWS., Conclusions: Inflammatory plasma biomarkers discriminate sepsis due to GN bacteremia or NEC and correlate with cardiorespiratory physiomarkers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kumar, Kausch, Gummadi, Fairchild, Abhyankar, Petri and Sullivan.)

Human islets can be transplanted into the portal vein for T1 diabetes, and a similar procedure is being used in a clinical trial for stem cell-derived beta-like cells. Efforts have been underway to find an alternative transplant site that will foster better islet cell survival and function. Although conceptually attractive, the subcutaneous (SC) site has yielded disappointing results, in spite of some improvements resulting from more attention paid to vascularization and differentiation factors, including collagen. We developed a method to transplant rat islets in a disk of type 1 collagen gel and found improved efficacy of these transplants. Survival of islets following transplantation (tx) was determined by comparing insulin content of the graft to that of the pre-transplant islets from the same isolation. At 14 days after transplantation, grafts of the disks had more than double the recovered insulin than islets transplanted in ungelled collagen. SC grafts of disks had similar insulin content to grafts in a kidney site and in epididymal fat pads. In vivo disks underwent contraction to 10% of initial volume within 24 h but the islets remained healthy and well distributed. Whole mount imaging showed that residual donor vascular cells within the islets expanded and connected to ingrowing host blood vessels. Islets (400 rat islet equivalents (IEQ)) in the collagen disks transplanted into an SC site of NOD scid IL2R gammanull (NSG) mice reversed streptozotocin (STZ)-induced diabetes within 10 days as effectively as transplants in the kidney site. Thus, a simple change of placing islets into a gel of collagen 1 prior to transplantation allowed a prompt reversal of STZ-induced diabetes using SC site., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Chorioamnionitis and early onset sepsis (EOS) in very low birth weight (VLBW,< 1500 g) infants may cause a systemic inflammatory response reflected in patterns of heart rate (HR) and oxygenation measured by pulse oximetry (SpO2). Identification of these patterns might inform decisions about duration of antibiotic therapy after birth., Objective: Compare early HR and SpO2 patterns in VLBW infants with or without early onset sepsis (EOS) or histologic chorioamnionitis (HC)., Study Design: Retrospective study of placental pathology and HR and SpO2 in the first 72 h from birth in relation to EOS status for inborn VLBW NICU patients 2012-2019., Result: Among 362 VLBW infants with HR and SpO2 data available, clinical, or culture-positive EOS occurred in 91/362 (25%) and HC in 81/355 (22%). In univariate analysis, EOS was associated with higher mean HR, lower mean SpO2, and less negative skewness of HR in the first 3 days after birth. HC was associated with higher standard deviation and skewness of HR but no difference in SpO2. In multivariable modeling, significant risk factors for EOS were mean HR, gestational age, HC, mean SpO2, and skewness of SpO2., Conclusion: HR and SpO2 patterns differ shortly after birth in VLBW infants exposed to HC or with EOS, likely reflecting a systemic inflammatory response.

Artificial intelligence (AI) offers tremendous potential to transform neonatology through improved diagnostics, personalized treatments, and earlier prevention of complications. However, there are many challenges to address before AI is ready for clinical practice. This review defines key AI concepts and discusses ethical considerations and implicit biases associated with AI. Next we will review literature examples of AI already being explored in neonatology research and we will suggest future potentials for AI work. Examples discussed in this article include predicting outcomes such as sepsis, optimizing oxygen therapy, and image analysis to detect brain injury and retinopathy of prematurity. Realizing AI's potential necessitates collaboration between diverse stakeholders across the entire process of incorporating AI tools in the NICU to address testability, usability, bias, and transparency. With multi-center and multi-disciplinary collaboration, AI holds tremendous potential to transform the future of neonatology., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Centromeres are crucial for chromosome segregation, but their underlying sequences evolve rapidly, imposing strong selection for compensatory changes in centromere-associated kinetochore proteins to assure the stability of genome transmission. While this co-evolution is well documented between species, it remains unknown whether population-level centromere diversity leads to functional differences in kinetochore protein association. Mice (Mus musculus) exhibit remarkable variation in centromere size and sequence, but the amino acid sequence of the kinetochore protein CENP-A is conserved. Here, we apply k-mer-based analyses to CENP-A chromatin profiling data from diverse inbred mouse strains to investigate the interplay between centromere variation and kinetochore protein sequence association. We show that centromere sequence diversity is associated with strain-level differences in both CENP-A positioning and sequence preference along the mouse core centromere satellite. Our findings reveal intraspecies sequence-dependent differences in CENP-A/centromere association and open additional perspectives for understanding centromere-mediated variation in genome stability., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Colorectal cancer (CRC) polygenic risk scores (PRS) may help personalize CRC prevention strategies. We investigated whether an existing PRS was associated with advanced neoplasia (AN) in a population undergoing screening and follow-up colonoscopy., Methods: We evaluated 10-year outcomes in the Cooperative Studies Program #380 screening colonoscopy cohort, which includes a biorepository of selected individuals with baseline AN (defined as CRC or adenoma ≥10 mm or villous histology, or high-grade dysplasia) and matched individuals without AN. A PRS was constructed from 136 prespecified CRC-risk single nucleotide polymorphisms. Multivariate logistic regression was used to evaluate the PRS for associations with AN prevalence at baseline screening colonoscopy or incident AN in participants with at least one follow-up colonoscopy., Results: The PRS was associated with AN risk at baseline screening colonoscopy ( P  = .004). Participants in the lowest PRS quintile had more than a 70% decreased risk of AN at baseline (odds ratio 0.29, 95% confidence interval 0.14-0.58; P < .001) compared to participants with a PRS in the middle quintile. Using a PRS cut-off of more than the first quintile to indicate need for colonoscopy as primary screening, the sensitivity for detecting AN at baseline is 91.8%. We did not observe a relationship between the PRS and incident AN during follow-up ( P  = .28)., Conclusion: A PRS could identify individuals at low risk for prevalent AN. Ongoing work will determine whether this PRS can identify a subset of individuals at sufficiently low risk who could safely delay or be reassured about noninvasive screening. Otherwise, more research is needed to augment these genetic tools to predict incident AN during long-term follow-up.

Objective: Antibiotic exposure increases the risk of morbidity and mortality in premature infants. Many centers use at least 48 hours of antibiotics in the evaluation of early-onset sepsis (EOS, <72 hours after birth), yet most important pathogens grow within 24 hours. We investigated the safety and efficacy of reducing empiric antibiotic duration to 24 hours., Design: Quality improvement study., Setting: A tertiary-care neonatal intensive care unit., Patients: Inborn infants <35 weeks gestational age at birth (ie, preterm) admitted January 2019 through December 2020., Intervention: In December 2019, we changed the recommended duration of empiric antibiotics for negative EOS evaluations from 48 hours to 24 hours., Results: Patient characteristics before and after the intervention were similar. After the intervention, 71 preterm infants (57%) with negative EOS evaluations received ≤24 hours of antibiotics, an increase from 15 (10%) before the intervention. These 71 infants comprised 77% of infants with negative EOS blood cultures after excluding those treated as clinical sepsis (≥5 days of antibiotics). For all negative EOS blood cultures, the mean treatment duration decreased by 0.5 days from 3.9 days to 3.4 days. This finding equated to 2.4 fewer antibiotic days per 100 patient days for negative EOS blood cultures but similar antibiotic days per 30 patient days (7.2 days vs 7.5 days). This measure did not change over time. Subsequent sepsis evaluations <7 days after a negative EOS blood culture did not increase. Excluding contaminants, the median time to positivity was 13.2 hours (range, 8-23) in 8 positive blood cultures., Conclusion: Implementation of a 24-hour antibiotic course for negative EOS evaluations safely reduced antibiotic exposure in 77% of infants <35 weeks gestational age at birth in whom EOS was ruled out. All clinically significant pathogens grew within 24 hours.

Background: A multicenter RCT showed that displaying a heart rate characteristics index (HRCi) predicting late-onset sepsis reduced mortality for VLBW infants. We aimed to assess whether HRCi display had a differential impact for Black versus White infants., Methods: We performed secondary data analysis of Black and White infants enrolled in the HeRO RCT. We evaluated the predictive performance of the HRCi for infants with Black or White maternal race. Using models adjusted for birth weight, we assessed outcomes and interventions for a race × randomization interaction., Results: Among 2607 infants, Black infants had lower birth weight, gestational age, length of stay, and ventilator days, while sepsis and mortality were similar. The HRCi performed equally for sepsis prediction in Black and White infants. We found no differential effect of randomization by race on sepsis, mortality, antibiotic days, length of stay, or ventilator days. However, there was a differential randomization effect by race for blood cultures per patient: White RR 1.11 (95% CrI 1.04-1.18), Black RR 1.00 (0.93-1.07)., Conclusions: The HRCi performed similarly for sepsis prediction in Black and White infants. Randomization to HRCi display increased blood cultures in White but not in Black infants, while the impact on other outcomes or interventions was similar., Impact: Predictive analytics, such as heart rate characteristics (HRC) monitoring for late-onset neonatal sepsis, should have equal impact among patients of different race. Infants with Black or White maternal race randomized to HRC display had similar outcomes, but randomization to the study arm increased a related clinical intervention, blood cultures, in White but not in Black infants. This study provides evidence of a differential effect of predictive models on clinical care by race. The work will promote consideration and analysis of equity in the implementation of predictive analytics., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Importance: The Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) randomized clinical trial sought to recruit 50 000 adults into a study comparing colorectal cancer (CRC) mortality outcomes after randomization to either an annual fecal immunochemical test (FIT) or colonoscopy., Objective: To (1) describe study participant characteristics and (2) examine who declined participation because of a preference for colonoscopy or stool testing (ie, fecal occult blood test [FOBT]/FIT) and assess that preference's association with geographic and temporal factors., Design, Setting, and Participants: This cross-sectional study within CONFIRM, which completed enrollment through 46 Department of Veterans Affairs medical centers between May 22, 2012, and December 1, 2017, with follow-up planned through 2028, comprised veterans aged 50 to 75 years with an average CRC risk and due for screening. Data were analyzed between March 7 and December 5, 2022., Exposure: Case report forms were used to capture enrolled participant data and reasons for declining participation among otherwise eligible individuals., Main Outcomes and Measures: Descriptive statistics were used to characterize the cohort overall and by intervention. Among individuals declining participation, logistic regression was used to compare preference for FOBT/FIT or colonoscopy by recruitment region and year., Results: A total of 50 126 participants were recruited (mean [SD] age, 59.1 [6.9] years; 46 618 [93.0%] male and 3508 [7.0%] female). The cohort was racially and ethnically diverse, with 748 (1.5%) identifying as Asian, 12 021 (24.0%) as Black, 415 (0.8%) as Native American or Alaska Native, 34 629 (69.1%) as White, and 1877 (3.7%) as other race, including multiracial; and 5734 (11.4%) as having Hispanic ethnicity. Of the 11 109 eligible individuals who declined participation (18.0%), 4824 (43.4%) declined due to a stated preference for a specific screening test, with FOBT/FIT being the most preferred method (2820 [58.5%]) vs colonoscopy (1958 [40.6%]; P < .001) or other screening tests (46 [1.0%] P < .001). Preference for FOBT/FIT was strongest in the West (963 of 1472 [65.4%]) and modest elsewhere, ranging from 199 of 371 (53.6%) in the Northeast to 884 of 1543 (57.3%) in the Midwest (P = .001). Adjusting for region, the preference for FOBT/FIT increased by 19% per recruitment year (odds ratio, 1.19; 95% CI, 1.14-1.25)., Conclusions and Relevance: In this cross-sectional analysis of veterans choosing nonenrollment in the CONFIRM study, those who declined participation more often preferred FOBT or FIT over colonoscopy. This preference increased over time and was strongest in the western US and may provide insight into trends in CRC screening preferences.

Background: Heart rate characteristics aid early detection of late-onset sepsis (LOS), but respiratory data contain additional signatures of illness due to infection. Predictive models using cardiorespiratory data may improve early sepsis detection. We hypothesized that heart rate (HR) and oxygenation (SpO 2 ) data contain signatures that improve sepsis risk prediction over HR or demographics alone., Methods: We analyzed cardiorespiratory data from very low birth weight (VLBW, <1500 g) infants admitted to three NICUs. We developed and externally validated four machine learning models to predict LOS using features calculated every 10 m: mean, standard deviation, skewness, kurtosis of HR and SpO 2 , and cross-correlation. We compared feature importance, discrimination, calibration, and dynamic prediction across models and cohorts. We built models of demographics and HR or SpO 2 features alone for comparison with HR-SpO 2 models., Results: Performance, feature importance, and calibration were similar among modeling methods. All models had favorable external validation performance. The HR-SpO 2 model performed better than models using either HR or SpO 2 alone. Demographics improved the discrimination of all physiologic data models but dampened dynamic performance., Conclusions: Cardiorespiratory signatures detect LOS in VLBW infants at 3 NICUs. Demographics risk-stratify, but predictive modeling with both HR and SpO 2 features provides the best dynamic risk prediction., Impact: Heart rate characteristics aid early detection of late-onset sepsis, but respiratory data contain signatures of illness due to infection. Predictive models using both heart rate and respiratory data may improve early sepsis detection. A cardiorespiratory early warning score, analyzing heart rate from electrocardiogram or pulse oximetry with SpO 2 , predicts late-onset sepsis within 24 h across multiple NICUs and detects sepsis better than heart rate characteristics or demographics alone. Demographics risk-stratify, but predictive modeling with both HR and SpO 2 features provides the best dynamic risk prediction. The results increase understanding of physiologic signatures of neonatal sepsis., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background Vascular access for ongoing hemodialysis often fails, frequently requiring repeated procedures to maintain vascular patency. While research has shown racial discrepancies in multiple aspects of renal failure treatment, there is poor understanding of how these factors might relate to vascular access maintenance procedures after arteriovenous graft (AVG) placement. Purpose To evaluate racial disparities associated with premature vascular access failure after percutaneous access maintenance procedures following AVG placement using a retrospective national cohort from the Veterans Health Administration (VHA). Materials and Methods All hemodialysis vascular maintenance procedures performed at VHA hospitals between October 2016 and March 2020 were identified. To ensure the sample represented patients who consistently used the VHA, patients without AVG placement within 5 years of their first maintenance procedure were excluded. Access failure was defined as a repeat access maintenance procedure or as hemodialysis catheter placement occurring 1-30 days after the index procedure. Multivariable logistic regression analyses were performed to calculate prevalence ratios (PRs) measuring the association between hemodialysis maintenance failure and African American race compared with all other races. Models controlled for vascular access history, patient socioeconomic status, and procedure and facility characteristics. Results In total, 1950 access maintenance procedures in 995 patients (mean age, 69 years ± 9 [SD], 1870 men) with an AVG created in one of 61 VHA facilities were identified. Most procedures involved African American patients (1169 of 1950, 60%) and patients residing in the South (1002 of 1950, 51%). Premature access failure occurred in 215 of 1950 (11%) procedures. When compared with all other races, African American race was associated with premature access site failure (PR, 1.4; 95% CI: 1.07, 1.43; P = .02). Among the 1057 procedures in 30 facilities with interventional radiology resident training programs, there was no evidence of racial disparity in the outcome (PR, 1.1; P = .63). Conclusion African American race was associated with higher risk-adjusted rates of premature arteriovenous graft failure after dialysis maintenance. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Forman and Davis in this issue.

Importance: Socioeconomic status affects pregnancy and neurodevelopment, but its association with hospital outcomes among premature infants is unknown. The Area Deprivation Index (ADI) is a validated measure of neighborhood disadvantage that uses US Census Bureau data on income, educational level, employment, and housing quality., Objective: To determine whether ADI is associated with neonatal intensive care unit (NICU) mortality and morbidity in extremely premature infants., Design, Setting, and Participants: This retrospective cohort study was performed at 4 level IV NICUs in the US Northeast, Mid-Atlantic, Midwest, and South regions. Non-Hispanic White and Black infants with gestational age of less than 29 weeks and born between January 1, 2012, and December 31, 2020, were included in the analysis. Addresses were converted to census blocks, identified by Federal Information Processing Series codes, to link residences to national ADI percentiles., Exposures: ADI, race, birth weight, sex, and outborn status., Main Outcomes and Measures: In the primary outcome, the association between ADI and NICU mortality was analyzed using bayesian logistic regression adjusted for race, birth weight, outborn status, and sex. Risk factors were considered significant if the 95% credible intervals excluded zero. In the secondary outcome, the association between ADI and NICU morbidities, including late-onset sepsis, necrotizing enterocolitis (NEC), and severe intraventricular hemorrhage (IVH), were also analyzed., Results: A total of 2765 infants with a mean (SD) gestational age of 25.6 (1.7) weeks and mean (SD) birth weight of 805 (241) g were included in the analysis. Of these, 1391 (50.3%) were boys, 1325 (47.9%) reported Black maternal race, 498 (18.0%) died before NICU discharge, 692 (25.0%) developed sepsis or NEC, and 353 (12.8%) had severe IVH. In univariate analysis, higher median ADI was found among Black compared with White infants (77 [IQR, 45-93] vs 57 [IQR, 32-77]; P < .001), those who died before NICU discharge vs survived (71 [IQR, 45-89] vs 64 [IQR, 36-86]), those with late-onset sepsis or NEC vs those without (68 [IQR, 41-88] vs 64 [IQR, 35-86]), and those with severe IVH vs those without (69 [IQR, 44-90] vs 64 [IQR, 36-86]). In a multivariable bayesian logistic regression model, lower birth weight, higher ADI, and male sex were risk factors for mortality (95% credible intervals excluded zero), while Black race and outborn status were not. The ADI was also identified as a risk factor for sepsis or NEC and severe IVH., Conclusions and Relevance: The findings of this cohort study of extremely preterm infants admitted to 4 NICUs in different US geographic regions suggest that ADI was a risk factor for mortality and morbidity after adjusting for multiple covariates.

Background: Gulf War Illness (GWI) is a chronic, multi-symptom disorder affecting 25%-32% of Gulf War veterans. Veterans with GWI disproportionately suffer from gastrointestinal (GI) disorders. Given the increasing evidence supporting a gut-brain axis, we explore the relationship between post-traumatic stress disorder (PTSD), GWI, and self-reported GI disorders among GW veterans., Methods: Veterans from the Gulf War Era Cohort and Biorepository responded to a mail-based survey (N = 1058). They were stratified by GWI (Centers for Disease Control definition) and PTSD status. This yielded three groups: GWI-, GWI+/PTSD-, and GWI+/PTSD+. Multivariable logistic regression adjusting for demographic and military characteristics examined associations between GWI/PTSD groups and GI disorders. Results were expressed as adjusted odds ratios (aOR) with 95% confidence intervals (95% CI)., Key Results: The most frequently reported GI disorders were irritable bowel syndrome (IBS), gastroesophageal reflux disease (GERD), and colon polyps (CP). The GWI+/PTSD+ group had a higher odds of these disorders than the GWI+/PTSD- group (aOR IBS  = 3.12, 95% CI: 1.93-5.05; aOR GERD  = 2.04, 95% CI: 1.44-2.90; aOR CP  = 1.85, 95% CI: 1.23-2.80), which had a higher odds of these disorders than the GWI- group (aOR IBS  = 4.38, 95% CI: 1.55-12.36; aOR GERD  = 2.51 95% CI: 1.63-3.87; aOR CP  = 2.57, 95% CI: 1.53-4.32)., Conclusions & Inferences: GW veterans with GWI and PTSD have significantly higher odds of specific self-reported GI disorders than the other groups. Given the known bidirectional influences of the gut and brain, these veterans may benefit from a holistic healthcare approach that considers biopsychosocial contributors to the assessment and management of disease., (© 2023 John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Objective: Scores to predict sepsis or define sepsis severity could improve care for very low birth weight (VLBW) infants. The heart rate characteristics (HRC) index (HeRO score) was developed as an early warning system for late-onset sepsis (LOS), and also rises before necrotizing enterocolitis (NEC). The neonatal sequential organ failure assessment (nSOFA) was developed to predict sepsis-associated mortality using respiratory, hemodynamic, and hematologic data. The aim of this study was to analyze the HRC index and nSOFA near blood cultures in VLBW infants relative to diagnosis and sepsis-associated mortality., Study Design: Retrospective, single-center study of VLBW infants from 2011 to 2019. We analyzed HRC index and nSOFA around blood cultures diagnosed as LOS/NEC. In a subgroup of the cohort, we analyzed HRC and nSOFA near the first sepsis-like illness (SLI) or sepsis ruled-out (SRO) compared with LOS/NEC. We compared scores by diagnosis and mortality during treatment., Results: We analyzed 179 LOS/NEC, 93 SLI, and 96 SRO blood culture events. In LOS/NEC, the HRC index increased before the blood culture, while nSOFA increased at the time of culture. Both scores were higher in nonsurvivors compared with survivors and in LOS/NEC compared with SRO. The nSOFA 12 hours after the time of blood culture predicted mortality during treatment better than any other time point analyzed (area under the curve 0.91)., Conclusion: The HRC index provides earlier warning of imminent sepsis, whereas nSOFA after blood culture provides better prediction of mortality., Key Points: · The HRC index and nSOFA provide complementary information on sepsis risk and sepsis-related mortality risk.. · This study adds to existing literature evaluating these risk scores independently by analyzing them together and in cases of not only proven but also suspected infections.. · The impact of combining risk models could be improved outcomes for premature infants.., Competing Interests: J.L.W. has served as a paid consultant for Evolve Biosystems. The other authors declare no conflict of interest., (Thieme. All rights reserved.)

The idea that we can detect subacute potentially catastrophic illness earlier by using statistical models trained on clinical data is now well-established. We review evidence that supports the role of continuous cardiorespiratory monitoring in these predictive analytics monitoring tools. In particular, we review how continuous ECG monitoring reflects the patient and not the clinician, is less likely to be biased, is unaffected by changes in practice patterns, captures signatures of illnesses that are interpretable by clinicians, and is an underappreciated and underutilized source of detailed information for new mathematical methods to reveal., (Copyright © 2022. Published by Elsevier Inc.)

Artificial intelligence may have a role in the early detection of sepsis in neonates. Machine learning can identify patterns that predict high or increasing risk for clinical deterioration from a sepsis-like illness. In developing this potential addition to NICU care, careful consideration should be given to the data and methods used to develop, validate, and evaluate prediction models. When an AI system alerts clinicians to a change in a patient's condition that warrants a bedside evaluation, human intelligence and experience come into play to determine an appropriate course of action: evaluate and treat or wait and watch closely. With intelligently developed, validated, and implemented AI sepsis systems, both clinicians and patients stand to benefit. IMPACT: This narrative review highlights the application of AI in neonatal sepsis prediction. It describes issues in clinical prediction model development specific to this population. This article reviews the methods, considerations, and literature on neonatal sepsis model development and validation. Challenges of AI technology and potential barriers to using sepsis AI systems in the NICU are discussed., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Antibiotics are widely used in very low-birth-weight infants (VLBW, <1500 g), and excess exposure, particularly to broad-spectrum antibiotics, is associated with significant morbidity. An antibiotic spectrum index (ASI) quantifies antibiotic exposure by relative antimicrobial activity, adding information to exposure measured by days of therapy (DOT). We compared ASI and DOT across multiple centers to evaluate differences in antibiotic exposures., Methods: We extracted data from patients admitted to 3 level-4 NICUs for 2 years at 2 sites and for 1 year at a third site. We calculated the ASI per antibiotic days and DOT per patient days for all admitted VLBW infants <32 weeks gestational age. Clinical variables were compared as percentages or as days per 1,000 patient days. We used Kruskal-Wallis tests to compare continuous variables across the 3 sites., Results: Demographics were similar for the 734 VLBW infants included. The site with the highest DOT per patient days had the lowest ASI per antibiotic days and the site with the highest mortality and infection rates had the highest ASI per antibiotic days. Antibiotic utilization varied by center, particularly for choice of broad-spectrum coverage, although the organisms causing infection were similar., Conclusion: An antibiotic spectrum index identified differences in prescribing practice patterns among 3 NICUs unique from those identified by standard antibiotic use metrics. Site differences in infection rates and unit practices or guidelines for prescribing antibiotics were reflected in the ASI. This comparison uncovered opportunities to improve antibiotic stewardship and demonstrates the utility of this metric for comparing antibiotic exposures among NICU populations.

Introduction: Germline variants in CDH1 are associated with elevated risks of diffuse gastric cancer and lobular breast cancer. It is uncertain whether there is an increased risk of colorectal neoplasia., Methods: This was a retrospective analysis of colonoscopy outcomes in patients with germline CDH1 pathogenic/likely pathogenic variants., Results: Eighty-five patients were included with a mean age of 46.9 years. Initial colonoscopy found adenomatous polyps in 30 patients (35.3%), including advanced adenomas in 9 (10.6%). No colorectal cancers were identified on index or subsequent colonoscopies (when available)., Discussion: CDH1 carriers have colorectal neoplasia identified at similar rates as in the general population. Despite potential difficulties after gastrectomy, colorectal cancer screening remains important in this population., (Copyright © 2022 by The American College of Gastroenterology.)