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Background Gene-environment interactions may enhance our understanding of hypertension. Our previous study highlighted the importance of considering psychosocial factors in gene discovery for blood pressure (BP) but was limited in statistical power and population diversity. To address these challenges, we conducted a multi-population genome-wide association study (GWAS) of BP accounting for gene-depressive symptomatology (DEPR) interactions in a larger and more diverse sample. Results Our study included 564,680 adults aged 18 years or older from 67 cohorts and 4 population backgrounds (African (5%), Asian (7%), European (85%), and Hispanic (3%)). We discovered seven novel gene-DEPR interaction loci for BP traits. These loci mapped to genes implicated in neurogenesis ( TGFA , CASP3 ), lipid metabolism ( ACSL1 ), neuronal apoptosis ( CASP3 ), and synaptic activity ( CNTN6 , DBI ). We also identified evidence for gene-DEPR interaction at nine known BP loci, further suggesting links between mood disturbance and BP regulation. Of the 16 identified loci, 11 loci were derived from African, Asian, or Hispanic populations. Post-GWAS analyses prioritized 36 genes, including genes involved in synaptic functions ( DOCK4 , MAGI2 ) and neuronal signaling ( CCK , UGDH , SLC01A2 ). Integrative druggability analyses identified 11 druggable candidate gene targets, including genes implicated in pathways linked to mood disorders as well as gene products targeted by known antihypertensive drugs. Conclusions Our findings emphasize the importance of considering gene-DEPR interactions on BP, particularly in non-European populations. Our prioritized genes and druggable targets highlight biological pathways connecting mood disorders and hypertension and suggest opportunities for BP drug repurposing and risk factor prevention, especially in individuals with DEPR.

Background: The beneficial impact of peritoneal dialysis (PD) catheter placement following cardiopulmonary bypass in young infants has been demonstrated. But the indications to start early peritoneal dialysis are not agreed upon., Methods: This retrospective single center study was conducted to evaluate the performance of a clinical strategy for early PD start. PD catheters were placed in the operating room (OR) following cardiopulmonary bypass (CPB). Those with prolonged CPB times (>180 minutes), post-operative (post-op) oligo-anuria and/or inability to achieve negative fluid balance in post-op 24 hours were evaluated as high-risk and selected for early PD start (PD +). All PD + were started within the first post-op 24 hours. Primary outcomes were 5% fluid accumulation at post-op 48 hours and severe acute kidney injury (AKI) at post-op day 5., Results: There were forty-nine newborns. Twenty-nine subjects were early PD (PD +) starts and twenty used the PD catheter as an abdominal drain (PD -). Baseline demographic data were similar. Both groups were oliguric during post-op first 8 hours (p= 0.906). The Early PD (+) group produced significantly less urine output during post-op day 1 (0.98 vs 3.02 ml/kg/hour; p= 0.001). At post-op 48 hours, early PD (+) group had similar prevalence of 5% fluid accumulation as early PD (-), 5 (16.7%) vs. 2 (7.41%), respectively (p= 0.427). Severe AKI incidence at post-op day 5 was similar between the groups (17.3% vs 5.0%; p=0.204). Time to extubation was longer for early PD (+) group compared to PD (-) group, 10.0 days [7.0;16.0] vs. 4.0 days [4.0;10.0] (p=0.017)., Conclusions: Persistent oliguria and inability to achieve negative fluid balance during initial post-op 24 hours may identify those newborns who will benefit from early PD. The first post-operative 8 hours was indiscriminative for this strategy. PD start may ameliorate the disadvantage for the designated group., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Nephrology.)

Background: To investigate the association between the timing of surgery from the day of NEC/SIP diagnosis and clinical outcomes in preterm infants. Study Design: A retrospective cohort study comparing clinical outcomes of infants undergoing laparotomy at three clinically relevant time points (less and more than 48 hours, 96 hours, and 168 hours [7 days]) following NEC/SIP diagnosis. Results: Infants with NEC/SIP ( N = 97) receiving surgical invention >96 hours (34/97) had significantly lower gestational age (25.5 weeks [24.0; 26.9] vs 27.0 [25.0; 31.3]; p = 0.006), had lower birth weight (687 grams [600; 902] vs 940 [710; 1495]; p <0.001), had pneumoperitoneum less often on the abdominal x-ray (29.4% vs 57.1%, p = 0.017), had hemorrhagic ( p = 0.04) and reparative ( p = 0.003) lesions more often on intestinal histopathology, had PDA diagnosed more often (76.5% vs 50.8%, p = 0.02), required assisted ventilation more frequently ( p = 0.013), and received parenteral nutrition for longer duration (112 days [76.5; 145] vs 65.0 [23.0; 112], p = 0.004) following surgery compared to the infants receiving surgical intervention before 96 hours ( n = 63/97). In NEC-only sub-cohort, infants receiving laparotomy >48 hours ( n = 29/75) had lower median gestational age, lower birth weight, less pneumoperitoneum, and higher acute kidney injury than those receiving surgery <48 hours. On logistic regression, the odds of death were not significantly different (OR 0.65 [0.28, 1.54], p = 0.32) for infants receiving laparotomy ≤48 hours following NEC/SIP compared to subjects undergoing surgery >48 hours. The odds of intestinal failure (>60 days of parenteral nutrition) were 4.5 times (CI 1.56, 14.3), p = 0.005) higher for those having surgery >96 hours from NEC/SIP diagnosis. Conclusion: There was no significant difference in death among infants receiving surgery within 48 hours following surgical NEC/SIP diagnosis compared to those receiving surgery at ≥ 48 hours of diagnosis. However, infants receiving surgery >96 hours were more likely to receive parenteral nutrition for longer time. A prospective study is needed to understand the continuous relationship between time to surgery and outcomes., Competing Interests: Conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective:  This study aimed to identify the clinical and growth parameters associated with retinopathy of prematurity (ROP) in infants with necrotizing enterocolitis (NEC) and spontaneous ileal perforation (SIP)., Study Design:  We conducted a retrospective cohort study that compared clinical data before and after NEC/SIP onset in neonates, categorizing by any ROP and severe ROP (type 1/2) status., Results:  The analysis included 109 infants with surgical NEC/SIP. Sixty infants (60/109, 55%) were diagnosed with any ROP, 32/109 (29.3%) infants (22% type 1 and 7.3% type 2) with severe ROP. On univariate analysis, those with severe ROP (32/109, 39.5%) were of lower median gestational age (GA, 23.8 weeks [23.4, 24.6] vs. 27.3 [26.3, 29.0], p  < 0.001), lower median birth weight (625 g [512, 710] vs. 935 [700, 1,180], p  < 0.001) and experienced higher exposure to clinical chorioamnionitis (22.6 vs. 2.13%, p  < 0.006), and later median onset of ROP diagnosis (63.0 days [47.0, 77.2] vs. 29.0 [19.0, 41.0], p  < 0.001), received Penrose drain placement more commonly (19 [59.4%] vs. 16 [34.0%], p  = 0.04), retained less residual small bowel (70.0 cm [63.1, 90.8] vs. 90.8 [72.0, 101], p  = 0.007) following surgery, were exposed to higher FiO 2 7 days after birth ( p  = 0.001), received ventilation longer and exposed to higher FiO 2 at 2 weeks ( p  < 0.05) following NEC and developed acute kidney injury (AKI) more often (25 [86.2%] vs. 20 [46.5%], p  = 0.002) than those without ROP. Those with severe ROP had lower length, weight for length, and head circumference z scores. In an adjusted Firth's logistic regression, GA (adjusted odds ratio [aOR] = 0.51, 95% confidence interval [CI]: [0.35, 0.76]) and diagnosis at later age (aOR = 1.08, 95% CI: [1.03, 1.13]) was shown to be significantly associated with any ROP., Conclusion:  Infants who develop severe ROP following surgical NEC/SIP are likely to be younger, smaller, have been exposed to more O 2 , develop AKI, and grow poorly compared with those did not develop severe ROP., Key Points: · Thirty percent of infants with NEC/SIP had severe ROP.. · Those with severe ROP had poor growth parameters before and after NEC/SIP.. · Risk factors based ROP prevention strategies are needed to have improved ophthalmic outcomes.., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: The coronavirus disease 2019 (COVID-19) pandemic has led to an association between COVID-19 and pediatric diabetes. Studies have indicated the increased likelihood of children with COVID-19 infection developing diabetes. Our objective was to assess not only the increase in pediatric diabetes at our hospital and identify possible risk factors, but also to correlate the psychosocial changes resulting from the pandemic with new-onset diabetes., Methods: We analyzed data from 58 children aged 1 to 18 years admitted to our hospital with new-onset diabetes between March 2020 and December 2021. The data included inflammatory biomarkers and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies (Abs), as well as the results of a lifestyle questionnaire., Results: The average number of hospital admissions per month for new-onset diabetes increased from 10 to 18 with the start of the pandemic. Of the 58 children in our analysis, 33% had positive SARS-CoV-2 IgG Ab, 31% had type 1 diabetes mellitus, and 62% had type 2 diabetes mellitus (T2DM). More than half (54%) were experiencing diabetic ketoacidosis. Those with T2DM were older, majority African American, had higher median body mass index (BMI) percentiles, and lower vitamin D levels. There were no significant correlations between any psychosocial risk factors and either diabetes type or SARS-CoV2 Ab status., Conclusion: Despite the increased incidence of new-onset diabetes among children in Mississippi during the pandemic, this study was unable to demonstrate a significant correlation between COVID-19 infection and new-onset diabetes. The findings of this study highlighted the correlation between increased BMI and type 2 diabetes, underscoring the significant problems of obesity and diabetes in our study region. Further research is warranted.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to 23 genes. Investigating these genes' functional implications shed light on neurological, thyroidal, bone metabolism, and hematopoietic pathways that necessitate future investigation for blood pressure management that caters to sleep health lifestyle. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausible nature of distinct influences of both sleep duration extremes in cardiovascular health. Several of our loci are specific towards a particular population background or sex, emphasizing the importance of addressing heterogeneity entangled in gene-environment interactions, when considering precision medicine design approaches for blood pressure management., Competing Interests: Declarations CONFLICT OF INTEREST C.L.M. has received funding from AstraZeneca not related to the current study. B.M.P. serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.C. receives consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier. D.A.L. has received support from Medtronic LTD and Roche Diagnostics for biomarker research not related to the current study. The remaining authors declare no competing interests.

Although both short and long sleep duration are associated with elevated hypertension risk, our understanding of their interplay with biological pathways governing blood pressure remains limited. To address this, we carried out genome-wide cross-population gene-by-short-sleep and long-sleep duration interaction analyses for three blood pressure traits (systolic, diastolic, and pulse pressure) in 811,405 individuals from diverse population groups. We discover 22 novel gene-sleep duration interaction loci for blood pressure, mapped to genes involved in neurological, thyroidal, bone metabolism, and hematopoietic pathways. Non-overlap between short sleep (12) and long sleep (10) interactions underscores the plausibility of distinct influences of both sleep duration extremes in cardiovascular health. With several of our loci reflecting specificity towards population background or sex, our discovery sheds light on the importance of embracing granularity when addressing heterogeneity entangled in gene-environment interactions, and in therapeutic design approaches for blood pressure management., Competing Interests: Conflict of Interest/Disclosures: C.L.M. has received funding from AstraZeneca not related to the current study. B.M.P. serves on the steering committee of the Yale Open Data Access Project funded by Johnson & Johnson. D.C. receives consultancy fees from Roche Diagnostics and Trimedics and speaker fees from Servier. D.A.L. has received support from Medtronic LTD and Roche Diagnostics for biomarker research not related to the current study. The remaining authors declare no competing interests.

Background: Outcomes of infants following surgical necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) categorized by the age of onset, interventions, and sex are not well defined., Methods: Retrospective comparison of infants categorized by age of onset (NEC at <10, 10-20, and >20 days) and SIP at <7 versus ≥7 days), sex, and intervention [Penrose Drain (PD) vs. laparotomy]., Results: A total of 114 infants had NEC and 37 had SIP. On multinomial logistic regression, infants with NEC/SIP onset >20 days had significantly lower odds of small bowel involvement (aOR = 0.07, 95% CI: 0.01-0.33, p = 0.001), higher necrosis (aOR = 3.59, 95% CI: 1.34-9.65, p = 0.012) and higher CRP (p = 0.004) than onset <10 days. Initial laparotomy was associated with more bowel loss (24.1 cm [12.3; 40.6] vs.12.1 [8.00; 23.2]; p = 0.001), small and large intestine involvement (47.1% vs 17.2%; p = 0.01), and ileocecal valve resection (42% vs. 19.4%; p = 0.036) than initial PD therapy. Females underwent fewer small bowel resections (52.3% vs 73.6%; p = 0.025) but had higher surgical morbidity (53.7% vs. 24.7%.; p = 0.001) than males., Conclusion: Clinical, radiological, and histopathological presentation and outcomes in preterm infants with surgical NEC/SIP are associated with age of disease onset, sex, and initial intervention., Impact: Neonates with surgical NEC onset >20 days had more severe necrosis, inflammation, kidney injury, and bowel loss than those with <10 days. Initial laparotomy was associated with later age onset, more bowel loss, and ileocecal valve resection compared to initial PD treatment, but not with differences in mortality or length of stay. Female sex was associated with lower maturity, more placental malperfusion, less often small bowel involvement, lower pre-NEC hematocrit as well as higher surgical morbidity than males. Whether the management of surgical NEC and SIP should differ by the age of onset requires further investigation., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: We aim to determine clinical risk factors for postoperative complications in preterm infants with surgical necrotizing enterocolitis (NEC) or spontaneous intestinal perforation (SIP)., Methods: A retrospective cohort study of preterm infants with surgical NEC or SIP to compare clinical factors between those with and without postoperative complications., Results: 78/109 (71.5%) infants had any complication following surgical NEC. Adhesions (20/35, 57.1%) and wound infection (6/35, 17.1%) were the most common single surgical complications. Patients with a single surgical complication (35/66, 53%) were significantly less likely to be exposed to antenatal steroids, more frequently had a jejunostomy, needed a central line longer, and had a longer length of stay than those without any surgical complication. Infants with > 1 surgical complication (43/71, 60.5%) included mainly females, and had AKI more frequently at NEC onset, lower weight z-scores and lower weight for length z- scores at 36 weeks PMA than those without any complications.On multinomial logistic regression, antenatal steroids exposure (OR 0.23 [CI 0.06, 0.84]; p = 0.027) was independently associated with lower risk and jejunostomy 4.81 (1.29, 17.9) was independently associated with higher risk of developing a single complication. AKI following disease onset (OR 5.33 (1.38, 20.6), P = 0.015) was independently associated with > 1 complication in surgical NEC/SIP infants., Conclusion: Infants with postoperative complications following surgical NEC were more likely to be female, have additional morbidities, and demonstrate growth failure at 36 weeks PMA than those without surgical complications. There was no difference in mortality between those with and without surgical complications.

Background: To study the gestational age-specific risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis (NEC)., Methods: Retrospective cohort study comparing gestational age (GA)-specific clinical data between infants without severe AKI (stage 0/1 AKI) and those with severe AKI (stages 2 and 3 AKI) stratified by GA ≤27 and >27 weeks., Results: Infants with GA ≤27 weeks had double the rate of severe AKI (46.3% vs. 20%). In infants with GA >27 weeks, male sex, outborn, and nephrotoxic medication exposure were associated with severe AKI. On multivariable logistic regression, in infants with GA ≤27 weeks, surgical NEC (OR 35.08 (CI 5.05, 243.73), p < 0.001) and ostomy (OR 6.2(CI 1.29, 29.73), p = 0.027) were associated with significantly higher odds of severe AKI. Surgical NEC infants with GA >27 weeks and severe AKI were significantly more likely to be outborn, have later NEC onset, need dopamine, and have longer hospitalization (158 days [110; 220] vs.75.5 days [38.8; 105]; p = 0.007 than those with non-severe AKI., Conclusion: In neonates with NEC, surgical intervention was associated with moderate-to-severe AKI in infants with GA ≤27 weeks and with longer hospitalization in infants with GA >27 weeks., Impact: In both cohorts need for surgery, stoma, cholestasis, and mechanical ventilation were associated with severe AKI; however, the infants with GA <27 weeks had twice the risk of severe AKI than GA >27 weeks group. The longer exposure to nephrotoxic medication and referral need were significant risk factors for AKI in GA >27 weeks group. GA-specific kidney protective and monitoring strategies to prevent AKI and its consequences are needed to improve the clinical outcomes in neonates with NEC. Understanding the risk factors and short- and long-term outcomes unique to different GA groups will help inform those strategies., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To compare the clinical outcomes in preterm infants following surgical necrotizing enterocolitis (sNEC) and spontaneous intestinal perforation (SIP)., Methods: Retro-spective comparison of clinical information in preterm infants with sNEC and SIP admitted between January, 2013 and December 31, 2018. The clinical outcomes were compared in two groups, including postoperative and brain injury detected on brain magnetic resonance imaging (MRI) after clinical and histopathological confirmation of the SIP and the NEC diagnosis., Results: 114 infants had sNEC, and 37 had SIP. Infants with SIP had lower median gestational age [25.1 weeks (23.5, 27.1) vs 26.6 (24.4, 31.0), P=0.03], an earlier mean (SD) age of disease onset [10.1 (11.3) days vs 19.6 (17.9); P<0.001] and lower maternal chorioamnionitis on placental pathology [4 (23.5%) vs 22 (68.8%); P=0.007), received more often Penrose drain therapy (54% vs 33%; P=0.03), had less median (IQR) bowel length loss [3.3 cm (1.72, 4.38) vs 21.4 (9.55, 35.3); P=<0.001] and had more often intact ileocecal valve (91.4% vs 65.7%; P=0.006] compared to those with sNEC. In addition, those with sNEC had lower median (IQR) weight z scores at the time of discharge [-1.88 (-2.80, -1.09) vs -1.14 (-2.22, -0.44); P=0.036] than SIP. There were no significant differences in postoperative ileus, duration of parenteral nutrition, surgical morbidity, length of stay, mortality, white matter, and grey matter injury on brain MRI at term equivalent age in preterm infants with SIP and sNEC., Conclusion: In our cohort, preterm infants with SIP and sNEC did not show significant differences in postoperative morbidity and brain MRI abnormalities at term equivalent age. sNEC had lower discharge weight z scores. Larger prospective studies are needed for confirmation of these findings.

Background: The clinical impact of the timing of surgery on outcomes in preterm infants with surgical necrotizing enterocolitis (NEC) is not well defined., Aim: We sought to investigate the impact of the different timing of surgery from the day of NEC diagnosis on clinical outcomes in preterm infants with surgical NEC., Study Design: Retrospective Cohort Study., Subjects: Preterm 75 infants admitted between January 2013 and December 31, 2018, with an NEC (Bell stage III) diagnosis., Outcomes: Comparison of clinical information by the timing of surgery at three different time points (less and more than 48 hours, 96 hours, and 168 hours) in preterm infants with surgical NEC., Results: 75 infants were included in the analysis. Those who received surgery after 48 hours (n= 29/75) had lower median gestational age, lower birth weight, had less pneumoperitoneum, were out born less frequently, had higher acute kidney injury, were intubated and ventilated more frequently, and had higher hemorrhagic and reparative lesions on histopathology than those receiving surgery after 48 hours. Infants receiving surgery after 96 hours had similar trends expect had significantly lower hematocrit and more prolonged parenteral nutrition dependence than less than 96 hours group. The infants receiving surgery after one week had significantly lower birth weight and had higher reparative changes and cholestasis than those receiving surgery < 1 week.There was no significant impact of surgery timing on the length of bowel loss, surgical morbidity, Bronchopulmonary dysplasia, white matter injury, and mortality., Conclusion: The infants receiving surgery later were young and smaller and received parenteral nutrition longer with no significant impact on morbidities and mortality. Our data point out that there are advantages of operating early with fewer morbidities which need further confirmation and evaluation in large multicentric prospective studies or clinical trials., Competing Interests: Conflicts of interest: The authors disclose no conflicts.

Our objective was to examine serum ferritin trends after conversion to permanent vascular access (PVA) among children who started hemodialysis (HD) using tunneled cuffed catheters (TCC). Retrospective chart reviews were completed on 98 subjects from 20 pediatric HD centers. Serum ferritin levels were collected at the creation of PVA and for two years thereafter. There were 11 (11%) arteriovenous grafts (AVG) and 87 (89%) arteriovenous fistulae (AVF). Their mean TCC use was 10.4 ± 17.3 months. Serum ferritin at PVA creation was elevated at 562.64 ± 492.34 ng/mL, increased to 753.84 ± 561.54 ng/mL ( p = < 0.001) in the first year and remained at 759.60 ± 528.11 ng/mL in the second year ( p = 0.004). The serum ferritin levels did not show a statistically significant linear association with respective serum hematocrit values. In a multiple linear regression model, there were three predictors of serum ferritin during the first year of follow-up: steroid-resistant nephrotic syndrome as primary etiology ( p = 0.035), being from a center that enrolled >10 cases ( p = 0.049) and baseline serum ferritin level ( p = 0.017). Increasing serum ferritin after conversion to PVA is concerning. This increase is not associated with serum hematocrit trends. Future studies should investigate the correlation of serum transferrin saturation and ferritin levels in pediatric HD patients.

Background: we sought to determine the clinical and growth parameters associated with retinopathy of prematurity (ROP) in infants with necrotizing enterocolitis (NEC) and spontaneous ileal perforation (SIP)., Methods: Retrospective cohort study comparing clinical information before and following NEC/SIP onset in neonates with and without severe ROP (Type 1 and 2)., Results: Those with severe ROP (32/109, 39.5%) had lower GA, BW, chorioamnionitis, later median onset of ROP diagnosis and received Penrose drain and had higher AKI, poor weight z scores, poor linear growth, longer duration of ventilation and higher FIo2 than those without ROP following NEC/SIP. The GA and diagnosis at later age remained significant for any ROP on multi regression modelling., Conclusion: The surgical NEC/SIP infants with severe ROP were more likely to be younger, smaller, had AKI, had higher oxygen exposure and poor weight gain and linear growth than those without severe ROP., Competing Interests: Conflicts of interest: The authors disclose no conflicts.

Objective: To determine the association of placental pathology with the severity of necrotizing enterocolitis (NEC) in preterm infants., Methods: This single-center matched case-control study included infants with NEC ( n  = 107) and gestational age and birth weight-matched controls ( n  = 130), born between 2013 and 2020. Placentas were evaluated according to the Amsterdam Placental Workshop Group Consensus Statement., Results: Acute histologic chorioamnionitis with the fetal response was significantly more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p  = 0.02). On regression model, infants with multiple placental pathologies (OR 2.16; 95% CI 1.01 - 4.73; p  = 0.04) and maternal vascular malperfusion (OR 2.2; 95% CI 1.12 - 4.51; p  = 0.02) had higher odds of either medical or surgical NEC than controls., Conclusion: Infants with multiple placental lesions, including placental inflammatory and vascular lesions, were at higher risk of medical or surgical NEC in the postnatal period.

Background: To determine the association of placental pathologic lesions with postoperative outcomes, survival, and white matter injury (WMI) in preterm infants with NEC., Methods: A retrospective chart review of 107 neonates with NEC (Bell stage > IIa) from Jan 2013- June 2020 was completed. Demographic, clinical, and outcome data were compared between infants with or without placental pathologic lesions., Results: In this cohort, 59/107 (55%) infants had medical NEC, and 48 (45%) had surgical NEC. The infants had a mean gestational age of 28.1±3.7 weeks and a birth weight of 1103±647 g. Maternal vascular malperfusion (82/107, 76.6%) and acute histological chorioamnionitis (42, 39.3%) were the most common pathological placental lesions. Acute histologic chorioamnionitis with fetal inflammatory response was more common in infants with surgical NEC vs. medical NEC (35.4% vs. 15.3%; p = 0.02). The NEC Infants with WMI on brain MRI scans had a significantly higher incidence of acute histological chorioamnionitis (52% vs. 27.8%; P = 0.04). No significant differences in mortality, length of stay and postoperative outcomes in neonates with and without acute histologic chorioamnionitis with fetal inflammatory response were noted. On unadjusted logistic regression, acute histologic chorioamnionitis without fetal inflammatory response was also associated with higher odds of WMI (OR 2.81; 95% CI 1.05-7.54; p = 0.039)., Conclusion: Acute histological chorioamnionitis without fetal inflammatory response was associated with higher odds of WMI in infants with NEC, with no significant impact on mortality and other postoperative outcomes.

Objective: We sought to investigate the clinical determinants of intestinal failure and death in preterm infants with surgical NEC., Methods: Retrospective comparison of clinical information between Group A = intestinal failure (Parenteral nutrition (PN) >90 days) and death and Group B = survivors and with PN dependence < 90 days in preterm infants with surgical NEC., Results: Group A (n = 99/143) had a lower mean gestational age (26.4 weeks [SD3.5] vs. 29.4 [SD 3.5]; p = 0.013), lower birth weight (873 gm [SD 427g] vs. 1425 gm [894g]; p = <0.001), later age of NEC onset (22 days [SD20] vs. 16 days [SD 17]; p = 0.128), received surgery later (276 hours [SD 544] vs. 117 hours [SD 267]; p = 0.032), had cholestasis, received dopamine (80.6% vs. 58.5%; p = 0.010) more frequently and had longer postoperative ileus time (19.8 days [SD 15.4] vs. 11.8 days [SD 6.5]; p = <0.001) and reached full feeds later (93 days [SD 45] vs. 44 [SD 22]; p = <0.001) than Group B.On multivariate logistic regression, higher birth weight was associated with lower risk (OR 0.35, 95% CI 0.15-0.82; p = 0.016) of TPN > 90 days or death. Longer length of bowel resected (OR 1.76, 95% CI 1.02-3.02; p = 0.039) and longer postoperative ileus (OR 2.87, 95% CI 1.26-6.53; p = 0.011) were also independently associated with TPN >90days or death adjusted for gestational age and antenatal steroid treatment., Conclusion: In preterm infants with surgical NEC, clinical factors such as lower birth weight, longer bowel loss, and postoperative ileus days were significantly and independently associated with TPN >90 days or death.

Objective: To determine risk factors and outcomes of necrotizing enterocolitis (NEC)-associated sepsis in infants with NEC., Methods: A retrospective review comparing demographic and clinical information in infants with and without NEC-associated sepsis (defined as positive blood culture at the time of NEC onset)., Results: A total of 209 infants with medical (n = 98) and surgical NEC (n = 111) had a median gestational age of 27 weeks (IQR 25; 30.5) and a median birth weight of 910 g [IQR 655; 1138]. Fifty of 209 (23.9%) infants had NEC-associated sepsis. Infants with NEC-associated sepsis had lower median GA (26.4 vs. 27.4 weeks; p = 0.01), lower birth weight (745 vs. 930 g; p = 0.009), were more likely mechanically ventilated [p < 0.001], received dopamine [p < 0.001], had more evidence of acute kidney injury [60% vs. 38.4%, p = 0.01], longer postoperative ileus (16 [13.0; 22.0] vs. 12 [8; 16] days; p = 0.006), higher levels of C-reactive protein, lower platelet counts, longer hospitalization compared to infants without NEC-associated sepsis. On multivariate regression, cholestasis was an independent risk factor for NEC-associated sepsis (OR 2.94; 95% CI 1.1-8.8, p = 0.038)., Conclusion: NEC-associated sepsis was associated with greater hemodynamic support, acute kidney injury, longer postoperative ileus, and hospitalization on bivariate analysis, and cholestasis was associated with higher odds of sepsis on multi regression analysis., Impact: NEC-associated sepsis was present in 24% of infants with NEC. Gram-positive bacteria, Gram-negative bacteria, and Candida were found in 15.3%, 10.5%, and 2.8% of cases, respectively. Infants with NEC-associated sepsis had a greater inflammatory response (CRP levels), received more blood transfusion before NEC onset, frequently needed assisted ventilation ionotropic support, and had acute kidney injury after NEC onset. NEC infants with Gram-negative sepsis had higher portal venous gas, received more platelet transfusions before NEC onset, and had higher CRP levels and lower median lymphocyte counts at 24 h after NEC onset than those with Gram-positive sepsis., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: To investigate gestational age (GA) specific hematological and transfusion response patterns in preterm infants following necrotizing enterocolitis (NEC)., Design: A retrospective study comparing hematological/transfusion information in three GA groups' infants: Group A ≤ 28 weeks. Group B 28-32 weeks, Group C > 32 weeks following necrotizing enterocolitis., Results: Group A infants responded with significantly higher WBC count, thrombocytopenia, higher absolute neutrophil, and higher absolute monocyte and lower absolute lymphocyte counts following NEC onset, received more blood transfusions before NEC onset (59.8 versus 30.0%; p  = .007), and had higher odds of surgical NEC (OR 3.39 [95% CI 1.19-10.38]; p  = .02) than group C. One unit increase in absolute lymphocyte count on the day, and 24 h following NEC was significantly associated with lower surgical NEC odds than groups C., Conclusion: The infant's in-group A had significantly different hematological response patterns following NEC than infants with higher gestational age (groups B and C).

Background: Although new approaches for data collection, such as mobile technology and teleresearch, have demonstrated new opportunities for the conduct of more timely and less costly surveys in community-based studies, literature on the feasibility of conducing cardiovascular disease research using mobile health (mHealth) platforms among middle-aged and older African Americans has been limited., Objective: The purpose of this study was to contribute to the knowledge regarding the penetrance of internet and mobile technologies, such as cellphones or smartphones in existing large cohort studies of cardiovascular disease., Methods: A digital connectedness survey was conducted in the Jackson Heart Study (JHS), a Mississippi-based African American cohort study, as part of the annual follow-up calls with participants from July 2017 to February 2019., Results: Of the 4024 participants contacted, 2564 (63.7%) completed the survey. Among survey respondents, 2262 (88.2%) reported use of internet or cellphone, and 1593 (62.1%) had a smartphone. Compared to nonusers (n=302), internet or cellphone users (n=2262) were younger (mean age 80.1, SD 8.0 vs 68.2, SD 11.3 years), more likely to be affluent (n=778, 40.1% vs n=39, 15.4%), and had greater than high school education (n=1636, 72.5% vs n=85, 28.1%). Internet or cellphone users were less likely to have cardiovascular disease history compared to nonusers (136/2262, 6.6% vs 41/302, 15.8%). The prevalence of current smoking and average BMI were similar between internet or cellphone users and nonusers. Among internet or cellphone users, 1316 (58.3%) reported use of email, 504 (22.3%) reported use of apps to track or manage health, and 1269 (56.1%) expressed interest in using JHS-developed apps., Conclusions: Our findings suggest that it is feasible to use mHealth technologies to collect survey data among African Americans already enrolled in a longitudinal study. Our findings also highlight the need for more efforts to reduce the age and education divide in access and use of internet and smartphones for tracking health and research in African American communities., (©Pramod Anugu, Md Abu Yusuf Ansari, Yuan-I Min, Emelia J Benjamin, Joanne Murabito, Karen Winters, Erica Turner, Adolfo Correa. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.11.2022.)

Background: To determine the clinical implications and gestation age-specific diagnostic predictability of pneumatosis in preterm infants with necrotizing enterocolitis (NEC)., Methods: A retrospective study on abdominal radiographs comparing clinical and radiological information in infants with and without pneumatosis., Result: Our findings disproved our hypothesis. Pneumatosis was seen more frequently in infants with higher gestational age [28.4 (26.1-32.4) vs. 26.4 (24.3-29) weeks; p < 0.001] and birth weight [1110 (762-1768) vs. 770 (645-1022) grams; p < 0.001] and were more likely delivered vaginally (39.1% vs. 21.7%, p = 0.01). Portal venous gas was seen frequently on radiographs (10.3% vs. 0%, p < 0.001), but not pneumoperitoneum (20.7% vs. 36.7%, p = 0.02). Infants with pneumatosis frequently developed acute kidney injury, with higher serum creatinine (16.5% vs. 4.5%, p = 0.02) and frequent oliguria (12.9% vs. 2.7 %; p = 0.043) and had higher C-reactive protein levels at 24 and 96 hours (p < 0.002). Receiver operating curves for pneumatosis showed GA >28 weeks and birth weight > 1000 gm to have a sensitivity of 58.6% and specificity of 72.5%., Conclusion: Contrary to our hypothesis, infants who developed pneumatosis during NEC were more mature with a higher gestational age and birth weight than those who did not.

Introduction: Addressing cardiovascular disease (CVD) risk factors is essential to reducing CVD burden in African Americans (AAs). Goal-striving stress (GSS), the stress associated with fears of failure, is particularly relevant to AAa in a society where their upward mobility is often blocked. Therefore, the purpose of this study was to assess the association between GSS and incident hypertension, diabetes, and obesity among AAs., Methods: Hazard regression models were used to assess the relationship between GSS and incident hypertension, diabetes, and obesity among 4,485 participants in the Jackson Heart Study., Results: Among men, those with high (vs. low) GSS were 41% less likely to become obese over a mean period of eight years: 0.59 (0.36, 0.95) p=.03., Discussion: Differences in health behaviors and in stress hormone responses may explain the stress-obesity association we found in men but not women. Future research should examine other factors that may explain this relationship.

Background: Readmission rate is an important quality measure and can inform patient care. However, readmission of S. aureus bacteremia in children requires further research., Methods: We performed a population-based longitudinal observational study using the State Inpatient Database from New York, Florida, and Washington, 2009-2015. Children aged 18 years or younger hospitalized with S. aureus bacteremia were included. The outcome of non-elective readmission was assessed by developing Cox proportional hazards regression models., Results: Of 1240 children with S. aureus bacteremia, 223 (18.0%) and 351 (28.3%) had non-elective readmission within 30 days and 90 days after discharge, respectively. On multivariable analysis, catheter related infection (hazard ratio, HR: 1.79, 95% confidence interval, CI: 1.31-2.45) was associated with 30-day readmission. The median cost of the original hospitalization for S. aureus bacteremia was $29 914 (interquartile range, IQR: $13 276-$71 284), and that of 30 day readmission was $10 956 (IQR: $5765-$24 753)., Conclusions: S. aureus bacteremia is associated with a high rate of readmission in children, particularly in those with catheter related infection. Hospitalization with S. aureus bacteremia and readmission are costly. Future research should seek interventions to improve outcomes of S. aureus bacteremia in children, and the results of this study can serve as a benchmark., (Copyright © 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Arteriovenous fistulae (AVF) and grafts (AVG) are preferred permanent vascular access (PVA) for chronic hemodialysis (HD) patients. Our objective was to examine the change in markers of HD efficacy after successful establishment of a PVA among children who started HD with a tunneled cuffed catheter (TCC)., Materials and Methods: Retrospective chart reviews were completed on patients from 20 pediatric dialysis centers. All patients used TCC prior to AVF/AVG, and each patient acted as his/her own control. Data on markers of HD efficacy (single-pool Kt/V, urea reduction ratio (URR), serum albumin and hematocrit (Hct)) were collected at the creation of AVF/AVG and for 2 years thereafter. Statistical methods included hypothesis testing and statistical modeling after adjusting for relevant demographic variables., Results: First PVA was created in 98 individual children: 87 (89%) were AVF and 11 (11%) were AVG. The mean TCC vintage prior to AVF/AVG was 10.4 ± 17.3 months. At 1-year follow-up, Kt/V improved by 0.15 ± 0.06 (p = 0.02) and URR improved by 4.54 ± 1.17% (p < 0.0001). Furthermore, PVA was associated with improved serum albumin by 0.31 ± 0.07 g/dL (p < 0.0001) and Hct by 2.80 ± 0.65% (p < 0.0001) at 1 year. These HD efficacy markers remained statistically significant at 2 nd -year follow-up. These observations were further supported by the adjusted models. Conversion to AVF was associated with statistically significant improvement in all four markers of HD efficacy at 1-year follow-up. This trend was not demonstrated for subjects who were converted to AVG., Conclusion: Switching to PVA was associated with improved markers of HD efficacy, single-pool Kt/V, URR, serum albumin, and Hct. This improvement was mostly demonstrated at 1 year and maintained for the 2 nd year. The potential differential impact of the type of PVA on the trajectory of markers of HD efficacy should be further investigated.

Background: To study the risk factors and outcomes of severe acute kidney injury (AKI) in neonates with necrotizing enterocolitis., Methods: Retrospective chart review of 202 neonates with necrotizing enterocolitis (NEC) (Bell stage >IIa) from 2013 to 2018. AKI was defined as per-modified neonatal Kidney Disease: Improving Global Outcomes criteria. Demographic, clinical, and outcome data were compared between neonates without severe AKI (stage 0 and 1 AKI) and those with severe AKI (stage 2 and 3 AKI)., Results: Severe AKI occurred in 66/202 (32.6%) of neonates after NEC diagnosis and after 61/104 (58.7%) of surgical NEC diagnoses. On adjusted model, surgical NEC [adjusted odds ratio (aOR) = 30.6; 95% confidence interval (CI) = 8.9, 130.6], outborn [aOR = 3.9; 95% CI = 1.54, 11.0], exposure to antenatal steroids [aOR = 3.0; 95% CI = 1.1, 8.9], and positive blood culture sepsis [aOR = 3.5; 95% CI = 1.3, 10.0] had increased odds for severe AKI. Those with severe AKI required longer hospitalization [124 days (interquartile range (IQR) 88-187) vs. 82 days (IQR 42-126), p < 0.001]., Conclusions: Severe AKI is common in neonates with NEC who require surgical intervention, are outborn, have positive blood culture sepsis, and receive antenatal steroids. Severe AKI is associated with a significantly longer length of hospitalization., Impact: Neonates with NEC, who are transferred from outside hospitals, require surgical NEC management, and/or have a positive blood culture at NEC onset are at the highest odds for severe (stages 2 and 3) AKI. Assessment of urine output is important for patients with NEC. Without it, 11% of those with severe AKI would have been misdiagnosed using serum creatinine alone. Kidney-protective strategies in the pre-, peri-, and postoperative period may improve the morbidity and mortality associated with severe AKI in neonates with NEC., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: Determine whether hematological and transfusion patterns following, the onset of NEC can identify infants likely to develop fulminant, fatal necrotizing enterocolitis (NEC)., Design: Determine hematological predictors of fulminant NEC., Results: Of 336 neonates with NEC, 35 (10%) who developed fulminant NEC were born with higher birth weights and more frequently developed radiologically evident pneumoperitoneumand/or portal venous gas. Following the diagnosis of NEC, these infants were more likely to rapidly develop thrombocytopenia, lymphopenia, neutropenia, and lower total white blood cell counts compared to medical/surgical non-fulminant type. They were also more likely to have received a red blood cell (RBC) transfusion (76.7% vs. 53.1%, p = 0.001) within 48 h after disease onset and platelet transfusion (24.2% vs. 11.7%; p = 0.03) before the onset of NEC., Conclusion: Neonates with fulminant NEC frequently developed thrombocytopenia, lymphopenia, neutropenia, and leukopenia, received RBC transfusions after or platelet transfusions before the onset of NEC developed the fulminant disease.