Clinical and Growth Correlates of Retinopathy of Prematurity in Preterm Infants with Surgical Necrotizing Enterocolitis and Intestinal Perforation.

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 FiO2 7 days after birth (p = 0.001), received ventilation longer and exposed to higher FiO2 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 O2, 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..

Genetic variants and effect modifiers of QT interval prolongation in patients with sickle cell disease.

BACKGROUND: Sickle cell disease (SCD) is a common inherited blood disorder among African Americans (AA), with premature mortality which has been associated with prolongation of the heart rate-corrected QT interval (QTc), a known risk factor for sudden cardiac death. Although numerous genetic variants have been identified as contributors to QT interval prolongation in the general population, their impact on SCD patients remains unclear. This study used an unweighted polygenic risk score (PRS) to validate the previously identified associations between SNPs and QTc interval in SCD patients, and to explore possible interactions with other factors that prolong QTc interval in AA individuals with SCD. METHODS: In SCD patients, candidate genetic variants associated with the QTc interval were genotyped. To identify any risk SNPs that may be correlated with QTc interval prolongation, linear regression was employed, and an unweighted PRS was subsequently constructed. The effect of PRS on the QTc interval was evaluated using linear regression, while stratification analysis was used to assess the influence of serum alanine transaminase (ALT), a biomarker for liver disease, on the PRS effect. We also evaluated the PRS with the two subcomponents of QTc, the QRS and JTc intervals. RESULTS: Out of 26 candidate SNPs, five risk SNPs were identified for QTc duration under the recessive model. For every unit increase in PRS, the QTc interval prolonged by 4.0 ms (95% CI: [2.0, 6.1]; p-value: <0.001) in the additive model and 9.4 ms in the recessive model (95% CI: [4.6, 14.1]; p-value: <0.001). Serum ALT showed a modification effect on PRS-QTc prolongation under the recessive model. In the normal ALT group, each PRS unit increased QTc interval by 11.7 ms (95% CI: [6.3, 17.1]; p-value: 2.60E-5), whereas this effect was not observed in the elevated ALT group (0.9 ms; 95% CI: [-7.0, 8.8]; p-value: 0.823). CONCLUSION: Several candidate genetic variants are associated with QTc interval prolongation in SCD patients, and serum ALT acts as a modifying factor. The association of a CPS1 gene variant in both QTc and JTc duration adds to NOS1AP as evidence of involvement of the urea cycle and nitric oxide metabolism in cardiac repolarization in SCD. Larger replication studies are needed to confirm these findings and elucidate the underlying mechanisms.

Gestational age-specific clinical correlates of acute kidney injury in preterm infants with necrotizing enterocolitis.

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.

Lower extremity symptoms and ankle-brachial index screening as predictors of cardiovascular outcomes in Black adults.

BACKGROUND: The prevalence of peripheral artery disease (PAD) and leg symptoms are higher in Black than White adults. We studied the effects of self-reported lower extremity symptoms and ankle-brachial indices (ABI) groups on outcomes. METHODS: Black participants in the Jackson Heart Study with baseline ABI and PAD symptom assessments (exertional leg pain by the San Diego Claudication questionnaire) were included. Abnormal ABI was < 0.90 or > 1.40. Participants were divided into (1) normal ABI, asymptomatic, (2) normal ABI, symptomatic, (3) abnormal ABI, asymptomatic, and (4) abnormal ABI, symptomatic to examine their associations with MACE (stroke, myocardial infarction, fatal coronary heart disease) and all-cause mortality, using Kaplan-Meier survival curves and stepwise Cox proportional hazard models adjusting for Framingham risk factors. RESULTS: Of 4586 participants, mean age was 54.6 ± 12.6 years, with 63% women. Compared with participants with normal ABI who were asymptomatic, participants with abnormal ABI and leg symptoms had highest risk of MACE (adjusted HR 2.28; 95% CI 1.62, 3.22) and mortality (aHR 1.82; 95% CI 1.32, 2.56). Participants with abnormal ABI without leg symptoms had higher risk for MACE (aHR 1.49; 95% CI 1.06, 2.11) and mortality (aHR 1.44; 95% CI 1.12, 1.99). Participants with normal ABI and no leg symptoms did not have higher risks. CONCLUSION: Among Black adults, the highest risk for adverse outcomes were in symptomatic participants with abnormal ABIs, followed by asymptomatic participants with abnormal ABIs. These findings underscore the need for further studies to screen for PAD and develop preventative approaches in Black adults with asymptomatic disease.

Assessing the effects of therapeutic combinations on SARS-CoV-2 infected patient outcomes: A big data approach.

BACKGROUND: The COVID-19 pandemic has demonstrated the need for efficient and comprehensive, simultaneous assessment of multiple combined novel therapies for viral infection across the range of illness severity. Randomized Controlled Trials (RCT) are the gold standard by which efficacy of therapeutic agents is demonstrated. However, they rarely are designed to assess treatment combinations across all relevant subgroups. A big data approach to analyzing real-world impacts of therapies may confirm or supplement RCT evidence to further assess effectiveness of therapeutic options for rapidly evolving diseases such as COVID-19. METHODS: Gradient Boosted Decision Tree, Deep and Convolutional Neural Network classifiers were implemented and trained on the National COVID Cohort Collaborative (N3C) data repository to predict the patients' outcome of death or discharge. Models leveraged the patients' characteristics, the severity of COVID-19 at diagnosis, and the calculated proportion of days on different treatment combinations after diagnosis as features to predict the outcome. Then, the most accurate model is utilized by eXplainable Artificial Intelligence (XAI) algorithms to provide insights about the learned treatment combination impacts on the model's final outcome prediction. RESULTS: Gradient Boosted Decision Tree classifiers present the highest prediction accuracy in identifying patient outcomes with area under the receiver operator characteristic curve of 0.90 and accuracy of 0.81 for the outcomes of death or sufficient improvement to be discharged. The resulting model predicts the treatment combinations of anticoagulants and steroids are associated with the highest probability of improvement, followed by combined anticoagulants and targeted antivirals. In contrast, monotherapies of single drugs, including use of anticoagulants without steroid or antivirals are associated with poorer outcomes. CONCLUSIONS: This machine learning model by accurately predicting the mortality provides insights about the treatment combinations associated with clinical improvement in COVID-19 patients. Analysis of the model's components suggests benefit to treatment with combination of steroids, antivirals, and anticoagulant medication. The approach also provides a framework for simultaneously evaluating multiple real-world therapeutic combinations in future research studies.

Community risks for SARS-CoV-2 infection among fully vaccinated US adults by rurality: A retrospective cohort study from the National COVID Cohort Collaborative.

BACKGROUND: While COVID-19 vaccines reduce adverse outcomes, post-vaccination SARS-CoV-2 infection remains problematic. We sought to identify community factors impacting risk for breakthrough infections (BTI) among fully vaccinated persons by rurality. METHODS: We conducted a retrospective cohort study of US adults sampled between January 1 and December 20, 2021, from the National COVID Cohort Collaborative (N3C). Using Kaplan-Meier and Cox-Proportional Hazards models adjusted for demographic differences and comorbid conditions, we assessed impact of rurality, county vaccine hesitancy, and county vaccination rates on risk of BTI over 180 days following two mRNA COVID-19 vaccinations between January 1 and September 21, 2021. Additionally, Cox Proportional Hazards models assessed the risk of infection among adults without documented vaccinations. We secondarily assessed the odds of hospitalization and adverse COVID-19 events based on vaccination status using multivariable logistic regression during the study period. RESULTS: Our study population included 566,128 vaccinated and 1,724,546 adults without documented vaccination. Among vaccinated persons, rurality was associated with an increased risk of BTI (adjusted hazard ratio [aHR] 1.53, 95% confidence interval [CI] 1.42-1.64, for urban-adjacent rural and 1.65, 1.42-1.91, for nonurban-adjacent rural) compared to urban dwellers. Compared to low vaccine-hesitant counties, higher risks of BTI were associated with medium (1.07, 1.02-1.12) and high (1.33, 1.23-1.43) vaccine-hesitant counties. Compared to counties with high vaccination rates, a higher risk of BTI was associated with dwelling in counties with low vaccination rates (1.34, 1.27-1.43) but not medium vaccination rates (1.00, 0.95-1.07). Community factors were also associated with higher odds of SARS-CoV-2 infection among persons without a documented vaccination. Vaccinated persons with SARS-CoV-2 infection during the study period had significantly lower odds of hospitalization and adverse events across all geographic areas and community exposures. CONCLUSIONS: Our findings suggest that community factors are associated with an increased risk of BTI, particularly in rural areas and counties with high vaccine hesitancy. Communities, such as those in rural and disproportionately vaccine hesitant areas, and certain groups at high risk for adverse breakthrough events, including immunosuppressed/compromised persons, should continue to receive public health focus, targeted interventions, and consistent guidance to help manage community spread as vaccination protection wanes.

Higher hospitalization and mortality rates among SARS-CoV-2-infected persons in rural America.

PURPOSE: Rural communities are among the most underserved and resource-scarce populations in the United States. However, there are limited data on COVID-19 outcomes in rural America. This study aims to compare hospitalization rates and inpatient mortality among SARS-CoV-2-infected persons stratified by residential rurality. METHODS: This retrospective cohort study from the National COVID Cohort Collaborative (N3C) assesses 1,033,229 patients from 44 US hospital systems diagnosed with SARS-CoV-2 infection between January 2020 and June 2021. Primary outcomes were hospitalization and all-cause inpatient mortality. Secondary outcomes were utilization of supplemental oxygen, invasive mechanical ventilation, vasopressor support, extracorporeal membrane oxygenation, and incidence of major adverse cardiovascular events or hospital readmission. The analytic approach estimates 90-day survival in hospitalized patients and associations between rurality, hospitalization, and inpatient adverse events while controlling for major risk factors using Kaplan-Meier survival estimates and mixed-effects logistic regression. FINDINGS: Of 1,033,229 diagnosed COVID-19 patients included, 186,882 required hospitalization. After adjusting for demographic differences and comorbidities, urban-adjacent and nonurban-adjacent rural dwellers with COVID-19 were more likely to be hospitalized (adjusted odds ratio [aOR] 1.18, 95% confidence interval [CI], 1.16-1.21 and aOR 1.29, CI 1.24-1.1.34) and to die or be transferred to hospice (aOR 1.36, CI 1.29-1.43 and 1.37, CI 1.26-1.50), respectively. All secondary outcomes were more likely among rural patients. CONCLUSIONS: Hospitalization, inpatient mortality, and other adverse outcomes are higher among rural persons with COVID-19, even after adjusting for demographic differences and comorbidities. Further research is needed to understand the factors that drive health disparities in rural populations.

Racial, Gender, and Neighborhood-Level Disparities in Pediatric Trauma Care.

BACKGROUND: Disparities in trauma outcomes and care are well established for adults, but the extent to which similar disparities are observed in pediatric trauma patients requires further investigation. The objective of this study was to evaluate the unique contributions of social determinants (race, gender, insurance status, community distress, rurality/urbanicity) on trauma outcomes after controlling for specific injury-related risk factors. STUDY DESIGN: All pediatric (age < 18) trauma patients admitted to a single level 1 trauma center with a statewide, largely rural, catchment area from January 2010 to December 2020 were retrospectively reviewed (n = 14,398). Primary outcomes were receipt of opioids in the emergency department, post-discharge rehabilitation referrals, and mortality. Multivariate logistic regressions evaluated demographic, socioeconomic, and injury characteristics. Multilevel logistic regressions evaluated area-level indicators, which were derived from abstracted home addresses. RESULTS: Analyses adjusting for demographic and injury characteristics revealed that Black children (n = 6255) had significantly lower odds (OR = 0.87) of being prescribed opioid medications in the emergency department compared to White children (n = 5883). Children living in more distressed and rural communities had greater odds of receiving opioid medications. Girls had significantly lower odds (OR = 0.61) of being referred for rehabilitation services than boys. Post hoc analyses revealed that Black girls had the lowest odds of receiving rehabilitation referrals compared to Black boys and White children. CONCLUSION: Results highlight the need to examine both main and interactive effects of social determinants on trauma care and outcomes. Findings reinforce and expand into the pediatric population the growing notion that traumatic injury care is not immune to disparities.

Antihypertensive effects of immunosuppressive therapy in autoimmune disease.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder that primarily affects women of childbearing age. While immune system dysfunction has been implicated in the development of hypertension (HTN) in SLE, the effect of immunomodulatory drugs on blood pressure (BP) control in SLE patients is unknown. In the present study, we hypothesized that first-line immunomodulatory therapies prescribed to SLE patients would have a beneficial impact on BP. We retrospectively analyzed the Research Data Warehouse containing de-identified patient data (n = 1,075,406) from the University of Mississippi Medical Center for all patients with a clinical diagnosis of SLE. BP responses were analyzed in SLE patients that were initially prescribed a single therapy (methotrexate, hydroxychloroquine, azathioprine, mycophenolate mofetil (MMF), or prednisone). Of the 811 SLE patients who met criteria, most were hypertensive (56%), female (94%), and black (65%). Individuals prescribed MMF or hydroxychloroquine had significantly decreased BP and improved BP control at follow-up (>7 days and <3 months after initial visit). Our results suggest that MMF and hydroxychloroquine have beneficial effects on BP, independent of adjunctive antihypertensive therapies and existing renal disease.

Clinical Correlates of Cerebellar Injury in Preterm Infants with Surgical Necrotizing Enterocolitis.

Objective: Determine the risk factors of cerebellar injury in infants with surgical necrotizing enterocolitis (NEC). Methods: Retrospective study compared clinical/pathological information between surgical NEC infants with and those without cerebellar injury. Results: Infants with cerebellar injury (21/65, 32.3%) had significantly more hemorrhagic and the reparative lesions on the intestinal histopathology, had patent ductus arteriosus (PDA) more often, received red cell transfusion frequently, had blood culture positive sepsis and grew gram positive organisms more often and had cholestasis frequently following NEC than those without cerebellar injury. On multilogistic regression, the positive blood culture sepsis (OR 3.9, CI 1.1-13.7, p = 0.03), PDA (OR 4.5, CI 1.0-19.9, p = 0.04) and severe hemorrhage (grade 3-4)(OR 16.9, CI 2.1-135.5, p = 0.007) were independently associated with higher risk of cerebellar injury. Conclusion: The cerebellar injury was most likely associated with positive blood culture sepsis following NEC, PDA, and severe hemorrhage lesions (grade 3-4) in infants with surgical NEC.

Clinical and histopathological correlates of intestinal repair in preterm infants following surgical necrotizing enterocolitis.

OBJECTIVE: We sought to determine the clinical and histopathological factors linked with intestinal repair and its correlation with clinical outcomes in preterm infants following surgical necrotizing enterocolitis (NEC). METHODS: A retrospective study has compared clinical and histopathological characteristics between preterm infants with histopathological reparative changes versus non-reparative changes in resected intestinal tissue following surgical treatment of NEC. Reparative changes were defined as microscopic evidence of neovascularization, increased fibroblasts or myofibroblasts, and epithelial regeneration during histopathological examination of the most affected area of resected intestinal tissue. RESULTS: The infants with reparative changes (53/148) had significantly lower median birth weight (725 [650-963] vs. 920 [690-1320]; p = .018), higher likelihood of patent ductus arteriosus (38/53 [71.7%] vs. 48/95 [50.5%]; p = .012), longer TPN days (99 [56-147] vs. 76.5 [39-112.5]; p = .034), higher CRP levels (7.3 [3.2-13] vs. 2.6 [1.1-7.8]; p = .011) at NEC onset, and more short bowel syndrome (27/53 [54.0%] vs. 28/95 [32.2%]; p = .012). Those with reparative changes also received more Penrose drain therapy (21/53 [39.6%] vs. 14/95 [14.7%]; p = .011) and had a longer median time to laparotomy (108 h [28-216] vs. 24 [12-96]; p = .003). Epithelial regeneration observed in 6/53 (11.3%) infants lagged fibroblast proliferation and neovascularization changes in the submucosa/muscularis intestinal layers. On a multivariable logistic regression model which included histopathological and clinical factors, inflammation with a percentage <25% area involvement, time from NEC diagnosis to surgery, and Apgar score < 6 at 5 min were independently and significantly associated with higher odds reparative changes. CONCLUSION: In neonates with surgical NEC, the histopathological findings in the resected bowel are significantly associated with clinical characteristics, other histopathological findings, and outcomes. The presence of reparative changes consistent with healing is significantly associated with Apgar score, Penrose drain therapy, longer time from NEC diagnosis to surgery, and lower burden of inflammation in the resected bowel tissue in multivariable analyses. Routine histopathological grading of resected bowel and optimal use of Penrose drain therapy warrant further investigation in the care of neonates with surgical NEC.

Clinical impact of severe acute kidney injury on post-operative and brain injury outcomes in preterm infants following surgical necrotizing enterocolitis.

BACKGROUND: To evaluate post-operative outcomes and white matter injury (WMI) using brain MRI at term equivalent in neonates with and without severe acute kidney injury (AKI) following surgical necrotizing enterocolitis (NEC). METHODS: A retrospective cohort study comparing neonates with severe (Stage 2/3) vs. other (no AKI/Stage 1) AKI using KDIGO classification with multivariable models assessing this association in the context of multiple systemic comorbidities. RESULTS: Of 103 neonates with surgical NEC, 60 (58%) had severe AKI. Those with severe AKI had lower birth weight (BW; 715 vs. 950 g; p = .023), more frequently treated with indomethacin (18.3 vs. 2.4%); p = .014), higher CRP levels at 24 h after NEC onset (14.4 [6.4-19.8] vs. 4.8 [1.6-13.4]; p = .005), higher presence of cholestasis (73.3 vs. 51.2%); p = .023), later age of NEC onset (14 vs. 7 d); p = .004), longer length of bowel resected (14.9 vs. 4.3 cm); p = .011), longer post-operative ileus days (14 vs. 9 d); p < .001), longer post-operative days at starting enteral feedings (15 vs. 10 d; p < .001), longer days of attainment of full enteral feedings (75 vs. 44.5 d; p = .008) and longer length of stay (140.5 vs. 94 d; p = .028) compared to those without severe AKI. Compared to infants without AKI by serum creatinine, those with AKI had significantly more cases of white matter abnormality (WMA; 90 vs. 36.6%; p < .001) and retinopathy of prematurity (63.9 vs. 35.3%; p = .017). In addition, the presence of AKI Stage 2 and 3 by serum creatinine was independently associated with higher odds of sustaining severe WMI level on an ordinal scale (OR = 6.2; 95% CI = (1.1-35.5); p = .041). CONCLUSIONS: Neonates with severe AKI following surgical NEC were more likely to experience longer post-operative morbidity and higher WMI by MRI at term.

Clinical Correlates of Moderate-to-Severe Bronchopulmonary Dysplasia in Preterm Infants following Surgical Necrotizing Enterocolitis.

OBJECTIVE: The aim of the study is to determine clinical correlates of moderate to severe bronchopulmonary dysplasia (BPD) in preterm infants following surgical necrotizing enterocolitis (NEC). STUDY DESIGN: This is a retrospective, single-center cohort study comparing patients with moderate to severe BPD to patients with non/mild BPD among surgical NEC infants. BPD was defined by NIH 2001 consensus definition. RESULTS: Of 92 consecutive neonates with surgical NEC, 77% (71/92) had moderate/severe BPD and 22% (21/92) had non/mild BPD. The patent ductus arteriosus (PDA) was significantly higher in those developing moderate/severe BPD (67.6% [48/71]) than non/mild BPD (28.6% [6/21]; p = 0.001). Postoperatively, infants with moderate/severe BPD had more severe acute kidney injury (AKI; 67.6 [48/71] vs. 28.6% [6/21]; p = 0.001), were intubated longer (40.5 [interquartile (IQR): 12, 59] vs. 6 days [IQR: 2, 13]; p <0.001), received more parenteral nutrition (109 [IQR: 77, 147] vs. 55 days [IQR: 19, 70]; p <0.001), developed higher surgical morbidity (46.5 [33/71] vs. 14.3% [3/21]; p = 0.008), had more intestinal failure (62.5 vs. 13.3%; p <0.001), required a longer hospital stay (161 [IQR: 112, 186] vs. 64 days [IQR: 20, 91]; p <0.001), and were more likely to need home oxygen. In a multivariable analysis, lower birth weight (OR = 0.3, [95% confidence interval (CI): 0.1-0.5]; p = 0.001), PDA (OR = 10.3, [95% CI: 1.6-65.4]; p = 0.014), and longer parenteral nutritional days (OR = 8.8; [95% CI: 2.0-43.0]; p = 0.005) were significantly and independently associated with higher odds of moderate/severe versus non-/mild BPD. CONCLUSION: Development of moderate/severe BPD occurred in the majority of preterm infants with surgical NEC in this consecutive series. Preterm infants with moderate/severe BPD were more likely to have a PDA before NEC. Development of moderate/severe BPD was associated with significantly greater burden and duration of postoperative morbidity following surgical NEC. Identifying surgical NEC infants at increased risk of moderate/severe BPD and developing lung protection strategies may improve surgical NEC outcomes. KEY POINTS: · Three-fourths of preterm infants experienced severe lung injury following surgical NEC.. · The infants with severe moderate/severe BPD were most likely associated with greater duration of postoperative morbidity.. · There is need to understand and develop lung protective strategies in infants with surgical NEC..

Microwave Ablation for Malignant Central Airway Obstruction: A Pilot Study.

BACKGROUND: Malignant central airway obstruction (CAO) is a debilitating complication of primary lung cancer and pulmonary metastases. Therapeutic bronchoscopy is used to palliate symptoms and/or bridge to further therapy. Microwave ablation (MWA) heats tissue by creating an electromagnetic field around an ablation device. We present a pilot study utilizing endobronchial MWA via flexible bronchoscopy as a novel modality for the management of malignant CAO. METHODS: Therapeutic bronchoscopy with a flexible MWA probe was performed in 8 cases. We reviewed tumor size, previous ablative techniques, number of applications, ablation time, amount of energy delivered, rate of successful recanalization, complications, and 30-day follow-up. RESULTS: Successful airway recanalization was achieved in all cases. No complications were noted. In 1 case, tumor in-growth within a silicone stent was ablated with no damage to the stent. DISCUSSION: Endobronchial MWA is a novel technique for tumor destruction while maintaining an airway axis. The oven effect and air gap around a tumor allow for safe and effective tissue devitalization and hemostasis without a thermal effect on structures surrounding the airway.

Brain injury in preterm infants with surgical necrotizing enterocolitis: clinical and bowel pathological correlates.

BACKGROUND: The objective of this study was to determine the risk factors and outcomes of white matter brain injury (WMBI) on magnetic resonance imaging (MRI) at term-equivalent age in infants with surgical necrotizing enterocolitis (NEC). METHODS: This retrospective study compared clinical/pathological information between infants with and those without WMBI. RESULTS: Out of 69 infants with surgical NEC, 17 (24.6%) had mild WMBI, 13 (18.8%) had moderate WMBI, and six (8.7%) had severe WMBI on the brain MRI. Several clinical factors (gestational age, more red blood cell (RBC) transfusions before NEC onset, pneumoperitoneum, earlier NEC onset age, postoperative ileus, acute kidney injury (AKI) by serum creatinine, postnatal steroids, hospital stay) and histopathological findings (necrosis, hemorrhage) had univariate associations with WMBI. Associations with RBC transfusion (odds ratio (OR) 23.6 [95% confidence interval (CI): 4.73-117.97]; p = 0.0001), age at NEC onset (OR 0.30 [95%CI: 0.11-0.84]; p = 0.021), necrosis (OR 0.10 [95%CI: 0.01-0.90]; p = 0.040), and bowel hemorrhage (OR 7.79 [95%CI: 2.19-27.72]; p = 0.002) persisted in multivariable association with grade 3-4 WMBI. The infants with WMBI had lower mean motor, cognitive, language scores, and higher ophthalmic morbidity at 2 years of age. CONCLUSIONS: The WMBI was most likely associated with earlier NEC onset, higher RBC transfusions, and less necrosis and greater hemorrhage lesions on intestinal pathology in preterm infants with surgical NEC. IMPACT: In preterm infants with surgical NEC, brain MRI showed injury in the white matter in 52%, gray matter in 10%, and cerebellar region in 30%. Preterm infants with severe WMBI (grade 3-4) had less necrosis and greater hemorrhagic lesions on histopathology of the bowel. Preterm infants with WMBI were more likely to have a more severe postoperative course, AKI, and longer length of hospitalization. Neuroprotective strategies to prevent brain injury in preterm infants with surgical NEC are needed with the goal of improving the neurodevelopmental outcomes.