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..

Advancing Science to Prevent Firearm Violence in Communities: A Process for Harmonizing Studies to Develop Research Infrastructure.

The Community Firearm Violence Prevention Network (CFVP Network), funded by the National Institutes of Health (NIH), supports a network of research projects that develop and test interventions through collaborations with community partners to prevent firearm violence, injury, and mortality. The CFVP Network presents a unique opportunity to accelerate the science of preventing firearm injuries. The data harmonization workgroup of the CFVP Network led the process of aligning studies across the three unique inaugural network projects, with particular attention to how the CFVP Network could address current gaps in the science. The goal of the data harmonization workgroup was to align study measures, assessment timelines, and data management and archival processes across projects to enable robust cross-project analyses that accelerate the science of preventing firearm injuries. To accomplish this goal, the workgroup established the infrastructure to facilitate cross-project data collection, data sharing and archiving, and analyses. Among the three inaugural network projects, the workgroup's process resulted in harmonizing two assessment timepoints (baseline and one year post-implementation) and 60 constructs (with 31 identical standardized constructs). These harmonized products provide opportunities for novel analyses across the network projects. We expect that the harmonized study infrastructure developed through this process will catalyze future research focused on preventing firearm injury, including and extending beyond CFVP Network projects. The CFVP data harmonization workgroup's process can serve as a model for future networks that seek to build the science in a particular area.

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.

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.

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.

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..

Systemic toxicities of trastuzumab-emtansine predict tumor response in HER2+ metastatic breast cancer.

The mechanism by which trastuzumab-emtansine (T-DM1) causes systemic toxicities apart from trastuzumab alone is currently unknown. We hypothesized that the systemic toxicities from T-DM1 may have been caused by the free and active maytansine released from the lysed HER2+ tumor cells, and if so, they may correlate with the response to treatment and eventually disease-free survival or patient outcome. In a retrospective, observational study, we evaluated 73 patients from three centers in the United States and Canada with advanced HER2+ breast cancer that received at least one dose of T-DM1. Toxicity grades were summed to create a corresponding toxicity sum score (TSS), and its association with clinical outcomes was analyzed. A higher TSS was significantly associated with longer progression-free survival with an HR = 0.66 [95% confidence interval [CI]: 0.47-0.92], P = .014, for each 1-point increase in the TSS score. Adjusted for baseline platelet count, aspartate transaminase and alanine transaminase, higher TSS remains significantly associated with longer progression-free survival with adjusted HR = 0.67 [95% CI: 0.47-0.93], P = .020. The analysis suggests that the systemic toxicities of T-DM1 were significantly correlated with its clinical efficacy. This is the first report to correlate the systemic toxicities of T-DM1 with clinical outcome. Further, this suggests that systemic toxicities of antibody-drug conjugates (ADCs) may serve as a predictive biomarker, particularly if noncleavable linkers are used. If confirmed in larger prospective studies, the present finding is significant because most ADCs do not have a biomarker predictive of clinical outcome other than the presence or absence of the antibody target.

Everolimus eluting bioresorbable vascular scaffolds for infrapopliteal critical limb ischemia: Moving beyond grasping at metal straws.

Consistent and durable patency and clinical benefit after initially successful infrapopliteal percutaneous balloon transluminal angioplasty (PTA) for critical limb ischemia remains an unmet need. Permanently implanted metallic stents for suboptimal initial infrapopliteal PTA results also have limited patency and clinical results as well as other drawbacks. In 48 critical limb ischemia patients with infrapopliteal lesions < 50 mm length, everolimus eluting bioresorbable vascular scaffolds (EEBVS) achieved 90% primary patency and freedom from clinically driven target lesion revascularization at 2 years follow-up with no late scaffold thrombosis.

The Association Between Neighborhood Social Vulnerability and COVID-19 Testing, Positivity, and Incidence in Alabama and Louisiana.

Racial/ethnic and socioeconomic disparities in COVID-19 burden have been widely reported. Using data from the state health departments of Alabama and Louisiana aggregated to residential Census tracts, we assessed the relationship between social vulnerability and COVID-19 testing rates, test positivity, and incidence. Data were cumulative for the period of February 27, 2020 to October 7, 2020. We estimated the association of the 2018 Social Vulnerability Index (SVI) overall score and theme scores with COVID-19 tests, test positivity, and cases using multivariable negative binomial regressions. We adjusted for rurality with 2010 Rural-Urban Commuting Area codes. Regional effects were modeled as fixed effects of counties/parishes and state health department regions. The analytical sample included 1160 Alabama and 1105 Louisiana Census tracts. In both states, overall social vulnerability and vulnerability themes were significantly associated with increased COVID-19 case rates (RR 1.57, 95% CI 1.45-1.70 for Alabama; RR 1.36, 95% CI 1.26-1.46 for Louisiana). There was increased COVID-19 testing with higher overall vulnerability in Louisiana (RR 1.26, 95% CI 1.14-1.38), but not in Alabama (RR 0.95, 95% CI 0.89-1.02). Consequently, test positivity in Alabama was significantly associated with social vulnerability (RR 1.66, 95% CI 1.57-1.75), whereas no such relationship was observed in Louisiana (RR 1.05, 95% CI 0.98-1.12). Social vulnerability is a risk factor for COVID-19 infection, particularly among racial/ethnic minorities and those in disadvantaged housing conditions without transportation. Increased testing targeted to vulnerable communities may contribute to reduction in test positivity and overall COVID-19 disparities.

Cost-effectiveness of CYP2C19-guided antiplatelet therapy in patients with acute coronary syndrome and percutaneous coronary intervention informed by real-world data.

Current guidelines recommend dual antiplatelet therapy (DAPT) consisting of aspirin and a P2Y12 inhibitors following percutaneous coronary intervention (PCI). CYP2C19 genotype can guide DAPT selection, prescribing ticagrelor or prasugrel for loss-of-function (LOF) allele carriers (genotype-guided escalation). Cost-effectiveness analyses (CEA) are traditionally grounded in clinical trial data. We conduct a CEA using real-world data using a 1-year decision-analytic model comparing primary strategies: universal empiric clopidogrel (base case), universal ticagrelor, and genotype-guided escalation. We also explore secondary strategies commonly implemented in practice, wherein all patients are prescribed ticagrelor for 30 days post PCI. After 30 days, all patients are switched to clopidogrel irrespective of genotype (nonguided de-escalation) or to clopidogrel only if patients do not harbor an LOF allele (genotype-guided de-escalation). Compared with universal clopidogrel, both universal ticagrelor and genotype-guided escalation were superior with improvement in quality-adjusted life years (QALY's). Only genotype-guided escalation was cost-effective ($42,365/QALY) and demonstrated the highest probability of being cost-effective across conventional willingness-to-pay thresholds. In the secondary analysis, compared with the nonguided de-escalation strategy, although genotype-guided de-escalation and universal ticagrelor were more effective, with ICER of $188,680/QALY and $678,215/QALY, respectively, they were not cost-effective. CYP2C19 genotype-guided antiplatelet prescribing is cost-effective compared with either universal clopidogrel or universal ticagrelor using real-world implementation data. The secondary analysis suggests genotype-guided and nonguided de-escalation may be viable strategies, needing further evaluation.

Ticagrelor monotherapy: When is mono-antiplatelet therapy (MAPT) equivalent or better?

Ischemic and bleeding events portend equivalently poor prognosis after percutaneous coronary intervention (PCI). Risk factors for these untoward events largely overlap limiting the "decoupling" of bleeding and ischemic risk. While individual patient risk scores inform the duration of guideline recommended dual antiplatelet therapy (DAPT) to strike the optimal balance between ischemic and bleeding risk, a promising additional approach is to tailor the regimens themselves. In higher risk patients, 1 month of aspirin plus ticagrelor followed by 23 months of ticagrelor monotherapy has equivalent bleeding and numerically improved ischemic risk than standard DAPT for 12 months followed by aspirin monotherapy in the GLOBAL LEADERS trial. In the TWILIGHT study of high ischemic and bleeding risk patients, 12 months of ticagrelor monotherapy had lower bleeding risk with equivalent ischemic risk as DAPT after 3 months of successful DAPT. Individual risk scores should be developed informing both optimal antiplatelet regimen such as ticagrelor monotherapy and treatment duration after PCI.

Safety and efficacy of paclitaxel drug-coated balloon treatment of femoropopliteal claudicants: Data and analytic methods matter.

Claudicants with femoropopliteal disease average 25% higher primary patency and reduced target lesion revascularization long term with crystalline paclitaxel eluting stent and balloon treatment compared to uncoated devices. In animal models, local and downstream tissues have detectable paclitaxel for greater than 180 days. Aggregate data meta-analyses of 28 randomized trials suggested 50-100% higher all-cause mortality with paclitaxel device treatment. In contrast, more complete ascertainment of follow-up and pooled individual patient data analyses do not find significantly increased mortality, a dose-mortality relationship, or an unexpected cause of death pattern with paclitaxel eluting device treatment in femoropopliteal claudicants.

A step forward in predicting anterograde crossing success for infrapopliteal chronic total occlusions.

Forty to fifty percent of critical limb ischemia patients have infrainguinal chronic total occlusions, frequently below-the-knee. With probabilities ranging from 21 to 90%, the Infrapop-CTO Score presented here in CCI predicts the likelihood of anterograde crossing of infrapopliteal chronic total occlusions (CTO). Based on cap morphology, occlusion length, calcification, and restenosis status, the score is easily assessed in the lab. An unfavorable Infrapop-CTO Score of 5 or 6, particularly coupled with convex proximal and distal caps (chronic total occlusion plaque [CTOP] Type IV), portends very low (21%) probability of successful anterograde crossing. An initial retrograde crossing strategy should be considered in these patients when technically feasible, followed by combined anterograde-retrograde intervention.

Costs of postoperative delirium with transcatheter aortic valve replacement: Improved yet still present.

Transcatheter aortic valve replacement (TAVR) is associated with a lower risk of postoperative delirium (PD) than surgical aortic valve replacement (SAVR) in patients aged ≥80, based on billing codes. Postoperative delirium remains a frequent problem after both SAVR and TAVR in clinical series and is costly. Improved pre-procedural prediction of PD risk would improve targeting of clinical care and allow testing of preventative and management strategies.

Clopidogrel pretreatment may reduce early acquired thrombocytopenia after transcatheter aortic valve replacement (TAVR).

Transcatheter aortic valve replacement (TAVR) causes early acquired thrombocytopenia on postoperative Days 1 and 2 in 30-50% of patients. While usually transient and rarely severe, early acquired thrombocytopenia is strongly associated with 30-day and 1-year post-TAVR outcomes, including mortality. Observation from a prospective registry suggests pretreatment with the P2Y12 receptor inhibitor clopidogrel before TAVR reduces the frequency and magnitude of early acquired thrombocytopenia. If a protective effect of clopidogrel pretreatment on early thrombocytopenia can be confirmed, then further study to determine if this translates into improved TAVR outcomes is warranted.

Intravascular ultrasound of normal left main arteries: Insights for stent optimization and standardization.

Left main (LM) lumen diameters >4 mm are the norm and diameter >4.5 mm is present in almost 50% of patients by intravascular ultrasound (IVUS). Normal LM minimum lumen area averages 14.1 mm2 for women and 16.2 mm2 for men, requiring an area stenosis of 57-63% for LM lesion to be hemodynamically significant using the prevailing criterion of 6 mm2 as a cut-off for revascularization. Incomplete LM visualization with IVUS is common (68%) without dedicated and specific LM IVUS techniques.

Embolic stroke of undetermined source and patent foramen ovale closure: Practice insights from meta-analysis?

Closure of patent foramen ovale (PFO) in embolic stroke of undetermined source (ESUS) reduces recurrent stroke compared with antiplatelet therapy in select patients but increases risk of atrial fibrillation. Device closure is an attractive option for young patients with an anatomically higher risk PFO and imaging proven ESUS. Benefit of PFO closure in ESUS compared with oral anticoagulation remains undefined.

Long-term survival prospects of patients undergoing percutaneous coronary intervention: Envisioning the future.

Implicit and largely intuitive survival predictions guide current clinical decision making after percutaneous coronary intervention (PCI). A model based on nine simple factors known after diagnostic catheterization but prior to PCI provides accurate prediction of five-year survival probability after PCI. Future prediction models and methods incorporating age and gender adjusted risk of death, cause of death (competing risks), and low prevalence but impactful comorbidities automatically implemented in electronic health records have the potential to further inform clinical decision-making and target therapies.