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Lay Summary Upadacitinib, a selective JAK-1 inhibitor, was used as rescue therapy for ulcerative colitis in the setting of pregnancy following use of mesalamine, vedolizumab, infliximab, and corticosteroids. This resulted in an uncomplicated live full birth without need for surgical intervention.

AbstractBackgroundHead and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi‐institutional study was designed to review outcomes for this rare patient population.MethodsRetrospective multi‐institutional review of FF reconstruction for midface ORN (2005–2022; n = 54).ResultsThe FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02).ConclusionIn this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

ImportanceProviding assisted ventilation during delayed umbilical cord clamping may improve outcomes for extremely preterm infants.ObjectiveTo determine whether assisted ventilation in extremely preterm infants (23 0/7 to 28 6/7 weeks’ gestational age [GA]) followed by cord clamping reduces intraventricular hemorrhage (IVH) or early death.Design, Setting, and ParticipantsThis phase 3, 1:1, parallel-stratified randomized clinical trial conducted at 12 perinatal centers across the US and Canada from September 2, 2016, through February 21, 2023, assessed IVH and early death outcomes of extremely preterm infants randomized to receive 120 seconds of assisted ventilation followed by cord clamping vs delayed cord clamping for 30 to 60 seconds with ventilatory assistance afterward. Two analysis cohorts, not breathing well and breathing well, were specified a priori based on assessment of breathing 30 seconds after birth.InterventionAfter birth, all infants received stimulation and suctioning if needed. From 30 to 120 seconds, infants randomized to the intervention received continuous positive airway pressure if breathing well or positive-pressure ventilation if not, with cord clamping at 120 seconds. Control infants received 30 to 60 seconds of delayed cord clamping followed by standard resuscitation.Main Outcomes and MeasuresThe primary outcome was any grade IVH on head ultrasonography or death before day 7. Interpretation by site radiologists was confirmed by independent radiologists, all masked to study group. To estimate the association between study group and outcome, data were analyzed using the stratified Cochran-Mantel-Haenszel test for relative risk (RR), with associations summarized by point estimates and 95% CIs.ResultsOf 1110 women who consented to participate, 548 were randomized and delivered infants at GA less than 29 weeks. A total of 570 eligible infants were enrolled (median [IQR] GA, 26.6 [24.9-27.7] weeks; 297 male [52.1%]). Intraventricular hemorrhage or death occurred in 34.9% (97 of 278) of infants in the intervention group and 32.5% (95 of 292) in the control group (adjusted RR, 1.02; 95% CI, 0.81-1.27). In the prespecified not-breathing-well cohort (47.5% [271 of 570]; median [IQR] GA, 26.0 [24.7-27.4] weeks; 152 male [56.1%]), IVH or death occurred in 38.7% (58 of 150) of infants in the intervention group and 43.0% (52 of 121) in the control group (RR, 0.91; 95% CI, 0.68-1.21). There was no evidence of differences in death, severe brain injury, or major morbidities between the intervention and control groups in either breathing cohort.Conclusions and RelevanceThis study did not show that providing assisted ventilation before cord clamping in extremely preterm infants reduces IVH or early death. Additional study around the feasibility, safety, and efficacy of assisted ventilation before cord clamping may provide additional insight.Trial RegistrationClinicalTrials.gov Identifier: NCT02742454

Objective: To investigate the longitudinal effects of COVID-19 on major vascular structures and parameters and clinical outcomes. Design: Observational prospective trial. Setting: Post-COVID-19 research clinic established by University of Louisville Division of Infectious Diseases. Participants: The study population consisted of 72 post-COVID-19 individuals and 11 non-COVID-19 infected participants in the control group. The participants were recruited from adult hospitals and from the community. The enrollment started in October 2020 and follow-up periods were at 3, 6, and 12 months from their initial COVID-19 diagnosis. Interventions: The participants were interviewed for medical and COVID-19 infection history. Samples of white blood cell (WBC), C-reactive protein (CRP), and D-dimer were taken at each visit. Certified sonographers performed vascular ultrasound on the study participants. Measurements and Main Results: Median intima-media thickness (IMT) was increased in mild/asymptomatic (0.80 mm) and severe/critical (0.90 mm) groups when compared with controls (0.60 mm; P < .001 for both groups). In the asymptomatic/mild group, 6-month median IMT (0.88 mm) was increased, compared with the 3-month group (0.75 mm), with P = .026. Increased age was associated with decreased mean arterial blood velocities (cm/s): common carotid ( r = −0.236, P = .032), internal carotid ( r = −0.208, P = .048), and subclavian artery mean velocity ( r = −0.357, P = .003). We did not find any instance of deep vein thrombosis. Median D-dimer, CRP, and WBC in the control group differed from asymptomatic/mild COVID-19 group ( P = .026, .011, and .003, respectively). Moreover, WBC in the asymptomatic/mild group and moderate COVID-19 group differed from severe/critical group ( P = .025 and P = .027, respectively); CRP also differed between asymptomatic/mild group and severe/critical group ( P = .014). Conclusions: There were differences in intima-media lumen thickness (IMT), arterial velocities, and inflammatory markers in post-COVID-19 patients. There was no instance of deep vein thrombosis in this post-COVID-19 study cohort. The increased IMT might infer atherosclerosis, which has shown to increase cardiovascular risks. It is not yet known whether the increase in IMT due to COVID should be treated in the same way as non-COVID-19 atherosclerosis—through statins, for example—or whether regular cardiovascular risk reduction would be useful. Clinical trial and mechanistic studies should be performed to further our understanding of COVID-19-related vascular pathologies.

Introduction: The predictive value of left atrial (LA) volume and reservoir function (ResF) post-atrial fibrillation (AF) ablation has been scarcely studied. Hypothesis: Abnormal LA volume and ResF post-ablation are associated with adverse cardiovascular events. Methods: We analyzed LA maximum (LAVImax) and minimum (LAVImin) volume index, and 2 measures of ResF, emptying fraction (LAEF) and expansion index (LAEI), prospectively measured at 3-month post-procedure in patients in sinus rhythm who underwent AF ablation between 2007-2016. Composite endpoint (CE) at follow up was all-cause mortality, cardiac hospitalization (heart failure or acute ischemic event) and stroke. Results: 792 patients were studied ( age 60±10 years, 25% women ; Table 1) . Over 7.5 years [IQR 3.0-9.7], 96 (12%) patients experienced CE, which was more prevalent in patients with enlarged LA and reduced ResF. Impaired LA volumes and ResF were each independently associated with CE ( Fig.1 ), even after adjustment for clinical, demographic and echo characteristics (Model A, Fig.2 ) (LAVImax ≥35 ml/m 2 : HR 2.15 [95% CI, 1.35-3.43], p=0.001; LAVImin≥20.5 ml/m 2 : HR 2.88 [1.77-4.69], p<0.0001; LAEF<39%: HR 2.00 [1.31-3.05], p=0.001; LAEI<65%: HR 1.95 [1.27-3.01], p=0.003). ResF measures (LAEF and LAEI) were incremental to LAVImax (all p<0.05), but not LAVImin (all p>0.05; Fig.2 ). In patients with normal LA (LAVImax <35 ml/m 2 ; n=408), increased LAVImin (≥20.5 ml/m 2 ) remained associated with CE (HR 3.11 [1.45-6.67], p=0.004) and cardiac hospitalization (HR 5.81 [1.87-18.01], p=0.002). These findings were independent of AF recurrence. Conclusions: In these patients, enlarged LA and impaired ResF at 3-month post-ablation were strongly associated with adverse cardiovascular outcomes, regardless of AF recurrence. Measures of LA ResF were incremental to LAVImax. Notably, LAVImin showed the strongest associations and even identified a high-risk subgroup among patients with non-dilated LA.

Background: A community based, cross-sectional echo survey demonstrated that pulmonary artery systolic pressure (PASP) increases with age and that PASP is associated with systemic arterial stiffness, Doppler estimated left ventricular (LV) filling pressures and lung function. Longitudinal assessment of PASP is needed to confirm cross-sectional observations. Objectives: To assess the whether PASP changes over time in longitudinally studied subjects and determine whether changes in PASP are associated with changes in systemic vascular stiffness, LV filling pressures or lung function. Methods: A random sample (n=2042) of the Olmsted County, MN population over age 40 underwent echo, record review and spirometry between 1997-2000 (Exam 1). A subset (n=1402) underwent repeat studies four years later (2001-2004; Exam 2). The current analysis includes the 723 subjects with paired PASP measurements. Changes ([[Unable to Display Character: ▵]]) in PASP, systemic arterial stiffness (pulse pressure; PP), LV filling pressure (E/e’) and lung function (% age/sex expected forced expiratory volume, %FEV1) were assessed. Results: At Exam 1, the median (interquartile range) age was 62 (69-70) years (62% female). Median time between exams was 48 (47-49) months. PASP increased from 26.1 (24.4-30.0) mmHg at Exam 1 to 28.0 (24.4-32.0) mmHg at Exam 2 (p<0.0001 by paired t test) for an average (SD) [[Unable to Display Character: ▵]] of 1.2 ± 5.5 mmHg. Adjusting for age and PASP at Exam 1, [[Unable to Display Character: ▵]]PASP was associated with [[Unable to Display Character: ▵]] age with an increase (parameter estimate (pe) ± standard error (se)) of 1.4±0.7 mmHg per year increase in age (p=0.046). [[Unable to Display Character: ▵]]PASP was not associated with sex and there was no age-sex interaction. Adjusting for age and PASP at Exam 1, [[Unable to Display Character: ▵]] age and Exam 1 values for PP, E/e or %FEV1 as appropriate, [[Unable to Display Character: ▵]]PASP was associated with [[Unable to Display Character: ▵]] PP (pe±se = 0.03±0.01 mmHg; p=0.01) [[Unable to Display Character: ▵]]E/e’ (pe±se = 0.21±0.06 mmHg, p=0.001) and [[Unable to Display Character: ▵]]%FEV1 (-0.09±0.02 mmHg, p<0.0001) suggesting that increases in PASP were related to increases in vascular stiffening, increases in LV filling pressures and declining lung function. Conclusions: In this longitudinal, population based study we find that PASP increases with aging and that increases in PASP over time are related to increases in systemic vascular stiffness and LV filling pressures and decreases in lung function.

Background: Impact of right ventricular (RV) overload on left ventricular (LV) performance has been demonstrated in Ebstein’s anomaly (EA). We have shown that LV radial strain (RS) in 83 EA patients was significantly less than in controls. We subsequently sought to evaluate LV strain after EA surgery. Methods: Systolic strain, strain rate (SR) and early diastolic strain rate (SRe) were retrospectively performed, using velocity vector imaging, in 24 repaired EA patients (age 35 ±12 years; 67% women) with LV ejection fraction >50%, preoperatively (median 5 days [1-145 days]) and postoperatively within 5 years at sequential follow-up (6 months-3 years). Repair of EA included tricuspid valve repair, valve replacement and bidirectional cavopulmonary anastomosis. A slope of change postoperatively was estimated for each subject using linear regression. A one-sample t-test of the mean slope=0 assessed average change per year. Results: Mean (standard deviation) and median (range) of preoperative LV RS was 36.5 +/- 11.4% and 36.3% (16.8-59.8) respectively. LV strain analyses are summarized in tables 1 and 2. Conclusions: LV RS improved significantly after EA surgery whereas circumferential strain (CS), SR and radial SR did not. This may reflect the change in RV and subsequently LV geometry after resolution of tricuspid regurgitation with EA surgery. Ongoing evaluation with deformational imaging may help to characterize if these changes are compensatory or maladaptive and may determine optimal timing for surgery. In the subgroup with the lowest RS, significant improvement postoperatively was not seen. This may suggest that surgery was performed too late to allow favorable remodeling.

Background: Non-cardiac surgery (NCS) in patients with severe aortic stenosis has traditionally been associated with high perioperative mortality. Aortic valve replacement is recommended prior to elective NCS, but the impact of this strategy has not been systematically assessed. Methods: A retrospective review was performed of all patients with severe aortic stenosis undergoing major NCS at Mayo Clinic between 2000 and 2013. Patients undergoing aortic valve intervention (AVI) prior to NCS were compared to those undergoing surgery without prior AVI (control). Patients undergoing emergency surgery were excluded. Primary endpoint was occurrence of major adverse cardiac events (MACE; combination of death, stroke, myocardial infarction, new/worsening heart failure, ventricular arrhythmia) within 30 days of NCS; secondary endpoints were mortality at 30 days and 1 year after NCS. Results: 180 patients (age 74.5 ± 10.5 years, 64% male) who underwent NCS within 12 months after AVI, were compared to 232 patients (age 76.6 ± 10.7 years, 56% male) in the control group. Patients undergoing AVI were more often symptomatic than controls (41% vs 26%, p = 0.002). MACE was significantly higher in the control group (21.6% vs 5.6%, p < 0.001), mainly due to the increased risk of heart failure in the postoperative period in this group (18.5% vs 2.2%, p < 0.001). There was no significant difference in the rate of myocardial infarction (1.7% vs 0.6%, p = 0.39), ventricular arrhythmia (0.9 % vs 0 %, p = 0.51) or stroke (0.9 % vs 0 %, p = 0.51). Kaplan-Meier assessment demonstrated no significant difference at 30 days but a reduction in 1 year mortality in the AVI group compared to the control group (Figure). Conclusions: Pre-operative AVI for severe aortic stenosis results in reduced heart failure and improved 1 year survival. However, other MACE and 30 day mortality appears unchanged. Pre-operative AVI should be considered in symptomatic patients, where the benefit of AVI is demonstrated to be greatest.

Introduction: Creation of an atrial septal defect via atrial septostomy (AS) is a therapeutic option traditionally utilized for PAH in settings where medical therapy was unavailable. Its utility in the context of progressive disease despite medical therapy remains incompletely understood. Hypothesis: AS may be a useful option in patients with symptomatic PAH despite medical therapy and may improve functional class. Methods: Single center retrospective study of all adult PAH patients receiving AS at a tertiary PAH referral center. Results: Eleven atrial septostomy procedures were performed in 8 patients who were refractory to maximal medical management. All patients were WHO functional class III or IV and average patient age was 40 ± 13 years with a female predominance (89%). Mean RA pressure was 18 ± 4 mm Hg with cardiac index of 2.28 ± 0.82 L/min/m 2 prior to AS. Mean pulmonary artery pressure was 63 mm Hg with a pulmonary artery saturation of 48% and average systolic blood pressure of 97 mm Hg. Baseline NT-proBNP was 5573 ± 4589 pg/ml with a mean 6 minute walk distance (6MWD) of 311 ± 131 meters. Five of the 11 procedures resulted in functional class improvement. Functional class change did not relate to change in 6MWD or NT-pro BNP level. Three patients had repeat AS due to spontaneous narrowing of the original septostomy, with a mean duration of 220 ± 135 days between procedures. One patient died within 30 days of the procedure and another at day 88 while one patient received a heart/lung transplant at day 42 post AS. Mean follow up was 243 ± 183 days. The REVEAL risk scores ranged from 10 to 15, with predicted 1 year survival from pre-septostomy clinical data ranging from 22% to 80% (mean predicted survival of 57%). Actual transplant free survival at 1 year was 63%. Conclusions: Selected patients at high risk for 1 year mortality may receive symptomatic benefit from atrial septostomy. One year mortality remains high, and not significantly different from that predicted by the REVEAL score. Atrial septostomy may be a palliative treatment option for patients who are refractory to maximal medical therapy but further long term investigation is necessary.