Low body mass index as a barrier to lung transplant in cystic fibrosis

RationaleLow body mass index (BMI) may influence lung transplant decisions for patients with advanced cystic fibrosis (CF) lung disease.ObjectiveDetermine whether patients with advanced CF lung disease and BMI ≤17 kg/m² are less likely to be listed for lung transplant or have a higher risk of death without listing compared to those with higher BMI.MethodsUsing merged United Network for Organ Sharing and CF Foundation Patient Registries, we identified adults with onset of advanced lung disease (FEV₁ ≤ 40% predicted) between May-2005 and December-2016. We analyzed survival using competing risks regression with cause-specific risks of listing for lung transplant and death without listing. BMI ≤ 17 kg/m² was our predictor.Measurements and main resultsAmong 5,121 CF patients with advanced lung disease, 23% were listed for lung transplant (n = 1,201), 23% died without listing (n = 1,190), and 44% were alive without listing (n = 2,730) as of December-2016. Patients with BMI ≤ 17 kg/m² were less likely to be listed for transplant (HR 0.69; 95% CI 0.57, 0.83) and more likely to die without listing (HR 1.63; 95% CI 1.41, 1.88). We identified important regional variations in the likelihood of referral and listing, based on BMI.ConclusionsPatients with advanced CF lung disease and BMI ≤ 17 kg/m² are less likely to be listed for lung transplant and have a higher risk of dying without listing, compared to those with higher BMI. Regional differences suggest access to transplant for malnourished CF patients may be limited by location.     

Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis

BackgroundElexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.MethodsLung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease. Patients were prospectively followed to evaluate treatment safety and effectiveness from initiation to July 20th, 2021.ResultsAmong the 331 patients with advanced CF pulmonary disease who initiated elexacaftor-tezacaftor-ivacaftor, 65 were lung transplant candidates (17 listed for transplantation, 48 considered for listing within 3 months). Median [IQR] follow-up time was 363 [329; 377] days. At the end of the follow-up period, two patients were transplanted five and 11 days following treatment initiation, two were listed for transplantation, and 61 no longer met transplantation criteria. Improvement in percent predicted forced expiratory volume in 1 s (ppFEV₁) at one month was +13.4% (95% confidence interval, 10.3%-16.5%; P < 0.0001) and remained stable thereafter. Treatment burden decreased substantially, with an 86% decrease in the need for intravenous antibiotics, 59% for oxygen therapy and 62% for non-invasive ventilation.ConclusionIn lung transplant candidates eligible for elexacaftor-tezacaftor-ivacaftor, the rapid improvement following initiation of treatment persisted over one year with a reduction in treatment burden and lung transplantation could be safely deferred in most patients.     

Postoperative complications in pediatric patients with cerebral palsy

Background/PurposeTo assess surgical outcomes of patients with cerebral palsy (CP) and if they differ from patients without CP.MethodsThe NSQIP-Pediatric database from 2012 to 2019 was used to compare differences in presenting characteristics and outcomes between patients with and without CP. Chi-square tests and multivariable logistic regression analysis were used to determine significance.Results119,712 patients, 433 (0.4%) with CP, 119,279 (99.6%) without, were identified. Patients with CP had more postoperative complications (19.4% vs. 6.9%, p < 0.001) with an OR of 3.2, (95%CI 2.5–4.1, p < 0.001) on univariable analysis. They underwent fewer laparoscopic procedures (79.1% vs. 90.8%, p < 0.001), had more readmissions (10.2% vs. 3.8%, p < 0.001), reoperations (5.1% vs. 1.2%, p < 0.001), and longer length of stays (LOS) (median 3 versus 1 day, p < 0.001). On multivariable analysis, having CP did not increase the odds of postoperative morbidity (OR 0.99, 95% CI 0.7–1.3), but higher ASA class, congenital lung malformation, gastrointestinal disease, coagulopathy, preoperative inotropic support, oxygen use, nutritional support, and steroid use significantly increase the odds of morbidity, all of which were more common in patients with CP.ConclusionPatients with CP have more postoperative complications, open procedures, and longer LOS. Patient complexity may account for these differences and risk-directed perioperative planning may improve outcomes.Level of EvidenceLevel IV.     

Cardiac retransplantation: is it justified in times of critical donor organ shortage? Long-term single-center experience

Objective: Survival after heart transplantation has improved significantly over the last decades. There are a growing number of patients that require cardiac retransplantation because of chronic allograft dysfunction. With regard to the critical shortage of cardiac allograft donors the decision to offer repeat heart transplantation must be carefully considered. Methods: Since 1983 a total of 807 heart transplantations have been performed at our institution. Among them 41 patients received cardiac retransplantation, 18 patients because of acute graft failure and 23 because of chronic graft failure. Data were analyzed for demographics, morbidity and risk factors for mortality. The acute and chronic retransplant group was compared to those patients undergoing primary transplantation. Results: The mean interval between primary transplantation and retransplantation was 1.9 days in the acute and 6.7 years in the chronic retransplant group. Mean follow-up was 6.9 years. Baseline characteristics were similar in the primary and retransplant group. Actuarial survival rates at 1, 3, 5 and 7 years after primary cardiac transplantation compared to retransplantation were 83, 78, 72 and 64% vs 53, 50, 47 and 36%, respectively (p < 0.001). Early mortality after acute retransplantation was significantly higher compared to late retransplantation (10/18, 55.6% vs 4/23, 17.4%, p = 0.011). Major causes of death were acute and chronic rejection, infection and sepsis. Conclusions: Cardiac retransplantation is associated with lower survival rates compared to primary transplantation. However, results after retransplantation in chronic graft failure are significantly better compared to acute graft failure. Therefore, we consider cardiac retransplantation in chronic graft failure a justified therapeutic option. In contrast, patients with acute graft failure seem to be inappropriate candidates for cardiac retransplantation.     

Strong toll-like receptor responses in cystic fibrosis patients are associated with higher lung function

BackgroundCystic fibrosis (CF) airways disease varies widely among patients with identical cystic fibrosis transmembrane conductance regulator (CFTR) genotypes. Robust airway inflammation is thought to be deleterious in CF; inter-individual variation in Toll-like receptor (TLR)-mediated innate immune inflammatory responses (TMIIR) might account for a portion of the phenotypic variation. We tested if TMIIR in people with CF are different than those of healthy controls, and whether higher TMIIR in people with CF are associated with reduced lung function.MethodsWe cultured whole blood from clinically stable subjects with CF (n = 76) and healthy controls (n = 45) with TLR agonists, and measured cytokine production and expression of TLR-associated genes. We tested for differences in TLR-stimulated cytokine levels between subjects with CF and healthy subjects, and for associations between cytokine and gene expression levels with baseline lung function (forced expiratory volume in one second percent predicted (FEV₁%)) and decline in FEV₁% over time.ResultsTMIIR in blood from subjects with CF were lower than in healthy controls. Expression of TLR regulators SARM1, TOLLIP, and AKT1 were downregulated in CF. In subjects with CF we found that lower TLR4-agonist-induced IL-8 was associated with lower FEV₁% at enrollment (p<0.001) and with greater five year FEV₁% decline (p<0.001).ConclusionsTMIIR were lower in people with CF relative to healthy controls; however, unexpectedly, greater whole blood TMIIR were positively associated with lung function in people with CF. These findings suggest a complex interaction between inflammation and disease in people with CF.     

Association of positive pre-transplant angiotensin II type 1 receptor antibodies with clinical outcomes in lung transplant recipients

IntroductionAutoantibodies against the angiotensin II type 1 receptor (AT1R-Ab) have been previously associated with de novo donor-specific antibody (DSA) formation in lung transplantation. However, data regarding the clinical significance of AT1R-Ab in long-term graft function after lung transplantation are lacking.MethodsSeventy-one patients who underwent lung transplantation between July 2016 and January 2020 were enrolled in this study. We examined the relationship between pre-transplant AT1R-Ab levels and graft function, clinical outcomes, and human leukocyte antigen (HLA) DSA levels during the first 3 years post-transplantation.ResultsSeventeen (23.9%) patients were AT1R-Ab-positive, and 54 (76.1%) were AT1R-Ab-negative. The median antibody value of the AT1R-Ab-positive group was 18 [18–22.5] U/mL, while that of the AT1R-Ab-negative group was 5.1 [3.5–8.0] U/mL (p < 0.001). There was no significant difference in the median acute cellular rejection (ACR) scores between the two groups (median [interquartile range] 1 [0.8–3] vs. 0.7 [0–1]; p = 0.145). However, there was a significant difference in the distribution of the ACR scores between the two groups (p = 0.015). Most (41.2%) patients in the pre-transplant AT1R-positive group scored above 1. The incidence of de novo DSA was also higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (52.9% vs. 20.4%, p = 0.009). The incidence of chronic lung allograft dysfunction (CLAD) within 3 years was significantly higher in AT1R-Ab-positive than in AT1R-Ab-negative patients (58.3% vs. 11.8%; p < 0.001). In the multivariate Cox regression analysis, AT1R-Ab positivity (hazard ratio, 9.46; 95% confidence interval, 2.89–30.94; p < 0.001) was significantly associated with early CLAD. Furthermore, Kaplan-Meier analysis showed that AT1R-Ab-positive patients had a shorter survival time (χ² = 39.62, p < 0.001).ConclusionHigh AT1R-Ab levels in the pre-transplant serum of lung recipients were associated with the development of de novo HLA-DSA, ACR, early CLAD, and short survival.     

Long-term outcomes of retransplantation after live donor liver transplantation: A Western experience

BackgroundDespite most liver transplants in North America being from deceased donors, the number of living donor liver transplants has increased over the last decade. Although outcomes of liver retransplantation after deceased donor liver transplantation have been widely published, outcomes of retransplant after living donor liver transplant need to be further elucidated.MethodWe aimed to compare waitlist outcomes and survival post-retransplant in recipients of initial living or deceased donor grafts. Adult liver recipients relisted at University Health Network between April 2000 and October 2020 were retrospectively identified and grouped according to their initial graft: living donor liver transplants or deceased donor liver transplant. A competing risk multivariable model evaluated the association between graft type at first transplant and outcomes after relisting. Survival after retransplant waitlisting (intention-to-treat) and after retransplant (per protocol) were also assessed. Multivariable Cox regression evaluated the effect of initial graft type on survival after retransplant.ResultsA total of 201 recipients were relisted (living donor liver transplants, n = 67; donor liver transplants, n = 134) and 114 underwent retransplant (living donor liver transplants, n = 48; deceased donor liver transplants, n = 66). The waitlist mortality with an initial living donor liver transplant was not significantly different (hazard ratio = 0.51; 95% confidence interval, 0.23–1.10; P = .08). Both unadjusted and adjusted graft loss risks were similar post-retransplant. The risk-adjusted overall intention-to-treat survival after relisting (hazard ratio = 0.76; 95% confidence interval, 0.44–1.32; P = .30) and per protocol survival after retransplant (hazard ratio:1.51; 95% confidence interval, 0.54–4.19; P = .40) were equivalent in those who initially received a living donor liver transplant.ConclusionPatients requiring relisting and retransplant after either living donor liver transplants or deceased donor liver transplantation experience similar waitlist and survival outcomes.     

Factors in childhood associated with lung function decline to adolescence in cystic fibrosis

BackgroundDespite improvements in general health and life expectancy in people with cystic fibrosis (CF), lung function decline continues unabated during adolescence and early adult life.MethodsWe examined factors present at age 5-years that predicted lung function decline from childhood to adolescence in a longitudinal study of Australasian children with CF followed from 1999 to 2017.ResultsLung function trajectories were calculated for 119 children with CF from childhood (median 5.0 [25%-75%=5.0–5.1]) years) to early adolescence (median 12.5 [25%-75%=11.4–13.8] years). Lung function fell progressively, with mean (standard deviation) annual change -0.105 (0.049) for forced vital capacity (FVC) Z-score (p<0.001), -0.135 (0.048) for forced expiratory volume in 1-second (FEV₁) Z-score (p<0.001), -1.277 (0.221) for FEV₁/FVC% (p<0.001), and -0.136 (0.052) for forced expiratory flow between 25% and 75% of FVC Z-score (p<0.001). Factors present in childhood predicting lung function decline to adolescence, in multivariable analyses, were hospitalisation for respiratory exacerbations in the first 5-years of life (FEV₁/FVC p = 0.001, FEF_25–75 p = 0.01) and bronchoalveolar lavage neutrophil elastase activity (FEV₁/FVC% p = 0.001, FEV₁ p = 0.05, FEF_25–75 p = 0.02). No examined factor predicted a decline in the FVC Z-score.ConclusionsAction in the first 5-years of life to prevent and/or treat respiratory exacerbations and counteract neutrophilic inflammation in the lower airways may reduce lung function decline in children with CF, and these should be targets of future research.     

Bariatric surgery improves access to renal transplantation and is safe in renal failure as well as after transplantation: A systematic review and meta-analysis

IntroductionEffective workup and listing of end-stage renal disease (ESRD) patients for renal transplantation, often with multiple co-morbidities, poses a challenge for transplant teams. Obesity is a common co-morbidity associated with adverse outcomes in ESRD and kidney transplant (KT) recipients. Bariatric and metabolic surgery (BMS) has long been established as a safe and effective treatment for morbid obesity. In this study, the authors aimed to evaluate the strength of evidence for both the efficacy and safety of bariatric surgery in patients with ESRD or kidney transplantation.MethodsA literature search was performed using key terms including “transplantation”, “kidney”, “renal”, “obesity”, and “bariatric”. Databases searched include MEDLINE, EMBASE and Web of Science from inception to date (April 2021). Methodological quality was assessed using the Newcastle-Ottawa tool. Selected articles were then categorised into patients awaiting waiting list acceptance, patients awaiting transplantation, patients undergoing simultaneous BMS + KT and patients undergoing BMS following a previous renal transplant. Summary effects are presented with a level of statistical significance and 95% Confidence Intervals.ResultsA total of 28 articles were selected following the literature search. Fourteen studies on patients awaiting listing (n = 1903), nine on patients on the KT waiting list (n = 196), a single study on simultaneous BMS and KT and ten studies on patients undergoing BMS following KT (n = 198). Mean change in BMI for patients awaiting listing was −11.3 kg/m² (95%CI: −15.3 to −7.3, p < 0.001), mean change in BMI for patients listed for KT was −11.2 kg/m 2(95%CI: −12.9 to −9.5, p 0.001) and mean change for patients with prior KT was −11.0 kg/m² (95%CI: −7.09 to −14.9, p < 0.001). The combined mortality rate for patients who had undergone both BMS and KT was 4% (n = 15).DiscussionThis review demonstrates BMS is both safe and efficacious in patients with ESRD prior to KT and in those post KT. It would enable difficult-to-list obese recipients the possibility to undergo transplantation and should be considered as part of the work up process.     

Upper and lower airway cultures in children with cystic fibrosis: Do not neglect the upper airways

BackgroundAirways of cystic fibrosis (CF) patients are colonised with bacteria early in life. We aimed to analyse differences between results of simultaneously taken upper airway (UAW) and lower airway (LAW) cultures, to describe clinical characteristics of patients with positive versus negative cultures and to follow up the patients with P. aeruginosa positive UAW cultures.MethodsBacteriological and clinical data from 157 children were collected during annual check up. The number of positive UAW and LAW cultures and correspondence between these results and clinical characteristics were analysed.ResultsPositive LAW and UAW cultures were found in 79.6% and 43.9% of patients respectively (p < 0.001). Patients with positive LAW cultures were significantly older (11.9 vs. 9.8 years, p < 0.05) and had more LAW symptoms (73.6% vs. 46.7%, p < 0.05), especially when P. aeruginosa was found. Patients with positive UAW cultures (especially S. aureus) had more nasal discharge (50.7% vs. 25.0%, p < 0.001). In 65% of patients with positive UAW and negative LAW culture for P. aeruginosa the next LAW became P. aeruginosa positive.ConclusionUAW cultures and LAW cultures differ in children with CF and there are differences in clinical characteristics between patients with positive versus negative culture results. P. aeruginosa positive UAW cultures appeared to precede positive LAW cultures in a substantial part of patients, suggesting some kind of cross-infection between the UAW and LAW.     

Clinical characteristics and outcomes associated with Inquilinus infection in cystic fibrosis

BackgroundMolecular diagnostics have led to the identification of a broad range of bacterial species in cystic fibrosis (CF) including Inquilinus. The clinical significance of Inquilinus in CF has not been thoroughly characterized.MethodsRetrospective, case-control study of persons with CF from two CF centers with at least one respiratory culture positive for Inquilinus spp. compared with age-matched CF controls with chronic Pseudomonas aeruginosa. Percent predicted forced expiratory volume in one second (ppFEV1) and body mass index percentile (BMI) were modeled from time of first positive culture up to 5 years later. Rates of pulmonary exacerbations were compared. Inquilinus isolates were genotyped to evaluate strain diversity.ResultsSeventeen patients with Inquilinus infection were identified with a mean age of 13 years at first positive culture. Most cases had multiple cultures positive for Inquilinus. ppFEV1 was not different between cases versus controls (80.2% vs 81.6%, p = 0.97 at baseline, 67.5% vs. 73.3%, p = 0.82 at 5 years). Patients were undernourished and BMI percentiles did not differ between groups (30.7% vs 43.4%, p = 0.32 at baseline, 37.9% vs. 37.6%, p = 0.98 at 5 years). There was no difference in the pulmonary exacerbation rate (3.0/year vs 2.5/year, p = 0.34). Genotyping showed diverse genetic strains between patients.ConclusionsInquilinus can present in childhood and is often associated with chronic infection in CF. Lung function and nutrition status at time of detection, lung function decline, and pulmonary exacerbation rates in Inquilinus cases were similar to those with chronic P. aeruginosa, a well-established CF pathogen.     

Lymphocyte responses to Mycobacterium tuberculosis and Mycobacterium bovis are similar between BCG-vaccinated patients with cystic fibrosis and healthy controls

BackgroundThe low rate of nontuberculous mycobacteria (NTM) among Brazilian patients with cystic fibrosis (CF) may be due to cross-reactive Bacille Calmette-Guérin (BCG) vaccination. In the present pilot study, we aimed to compare the lymphocyte responses against Mycobacterium tuberculosis(Mtb) and Mycobacterium bovis (BCG) in BCG-vaccinated CF patients and healthy controls.MethodsThe lymphocyte responses of CF patients (n = 10) and healthy controls (n = 10) were assessed in terms of lymphocyte proliferation index (LPI), using flow cytometry. Median rates of each cell subtype - CD4, CD8, γδ T cells and CD19 (B) cells - were also determined.ResultsMedian LPIs (CF vs. controls) were 22.9% vs. 13.0% (p = 0.481) and 23.1% vs. 17.6% (p = 0.481), upon stimulation with Mtb and BCG, respectively. Both groups had a predominant CD4 T cell response to Mtb (median rate = 82.5% vs. 79.7%; p = 0.796) and BCG (LPI = 84.3% vs. 83.0%; p = 0.853), which were significantly higher than the CD8, CD19 and γδ responses within both groups. CF patients tended to have a higher CD8 T cell response upon stimulation with the phytohemagglutinin mitogen than healthy controls (median rate = 42.8% vs. 31.7%, p = 0.075).ConclusionThe responses of BCG-vaccinated CF patients to Mtb and BCG are at least similar to those of healthy individuals. These are probably memory responses elicited by the BCG vaccination, which can cross-react with NTM and may explain the low frequency of NTM lung infection in our CF center.     

Cardiac retransplantation in children

Background

Experience with pediatric cardiac retransplantation is limited. Outcomes should be inspected to insure proper use of donor hearts.

Methods

Of 152 pediatric heart transplantations, we performed 20 retransplants in 17 children (3 had a second retransplant). The retransplant children were older than the primary transplant children (11.1 ± 4.4 years versus 7.1 ± 6.0 years; p = 0.005). Excluding 1 early retransplant, the interval from primary transplant to retransplant was 5.5 ± 3.3 years (range, 1.1 to 11.1). The retransplant patients were clinically more ill than the primary transplant patients (United Network for Organ Sharing status I, 75% versus 63%; mechanical circulatory support or dialysis, 20% versus 3.8%).

Results

Donor ischemia time (188 versus 165 minutes) and cardiopulmonary bypass time (127 versus 127 minutes) were not significantly different for the retransplant patients. Excluding 1 retransplant patient who required a tracheostomy, days on the ventilator (2.7 versus 2.7), days on inotropic support (3.0 versus 3.2), intensive care unit days (7.2 versus 6.7), and hospital days (15.9 versus 13.8) were similar in the retransplant group. Freedom from rejection at 90 days and 1 year was not different in the retransplant patients. Actuarial patient survival in the patients undergoing first retransplant was similar to the primary transplant patients at 30 days (95% versus 94.7%), 1 year (94.1% versus 80.7%), and 3 years (78.4% versus 73.1%). Two of 3 children receiving a third transplant died within 1 year of redo retransplantation.

Conclusions

Cardiac retransplantation can be performed in children with results comparable with those for primary transplantation despite increased clinical acuity. These early results suggest that cardiac retransplantation in children is a reasonable therapeutic option. Children with repeat retransplantation do not fare as well.     

Clinical judgment versus lung allocation score in predicting lung transplant waitlist mortality

Canadian lung transplant centers currently use a subjective and dichotomous “Status” ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P = .0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P < .001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS ≥ 37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.     

Tobacco smoke exposure limits the therapeutic benefit of tezacaftor/ivacaftor in pediatric patients with cystic fibrosis

ObjectivesTobacco smoke exposure reduces CFTR functional expression in vitro and contributes to acquired CFTR dysfunction. We investigated whether it also inhibits the clinical benefit of CFTR modulators, focusing on tezacaftor/ivacaftor, approved in February 2018 for individuals with CF age ≥12 years.MethodsA retrospective longitudinal analysis of encounter-based data from the CF Foundation Patient Registry (2016–2018) compared the slope of change in lung function (GLI FEV₁% predicted) before and after tezacaftor/ivacaftor initiation in smoke-exposed vs unexposed age-eligible pediatric patients. Tobacco smoke exposure (Ever/Never) was determined from caregiver self-report. Statistical analyses used hierarchical linear mixed modeling and fixed effects regression modeling.ResultsThe sample included 6,653 individuals with a total of 105,539 person-period observations. Tezacaftor/ivacaftor was prescribed to 19% (1,251) of individuals, mean age 17 years, mean baseline ppFEV₁ 83%, 28% smoke-exposed. Tezacaftor/ivacaftor users who were smoke-exposed had a lower baseline ppFEV₁ and experienced a greater lung function decline. Over two years, the difference in ppFEV₁ by smoke exposure among tezacaftor/ivacaftor users increased by 1.2% (7.6% to 8.8%, p<0.001). In both mixed effects and fixed effects regression models, tezacaftor/ivacaftor use was associated with improved ppFEV₁ among unexposed individuals (1.2% and 1.7%, respectively; p<0.001 for both) but provided no benefit among smoke-exposed counterparts (0.3%, p = 0.5 and 0.6%, p = 0.07, respectively).ConclusionTobacco smoke exposure nullifies the therapeutic benefit of tezacaftor/ivacaftor among individuals with CF aged 12–20 years old. To maximize the therapeutic opportunity of CFTR modulators, every effort must be taken to eliminate smoke exposure in CF.     

Associations of cephalad drainage in neonatal veno-venous ECMO – A mixed-effects,propensity score adjusted retrospective analysis of 20 years of ELSO data

BackgroundNeurologic complications can occur during neonatal Veno-Venous (VV) ECMO. The addition of a cephalad drainage cannula (i.e., VVDL+V) to dual lumen cannulation (i.e., VVDL) has been advocated to reduce such complications, but previous studies have presented mixed results.MethodsData from the ECMO Registry of the Extracorporeal Life Support Organization was used to extract all neonates (≤28 days old) who underwent VV ECMO for respiratory support between 2000 and 2019. Primary outcomes were mortality, conversion to Veno-Arterial (VA) ECMO, pump flows, and complications. A mixed-effects, propensity score adjusted analysis was performed.Results4,275 neonates underwent VV ECMO, 581 (13.6%) via VVDL+V cannulation, and 3,694 (86.4%) via VVDL. On unadjusted analyses, VVDL+V patients had higher rates of mortality (25.5% vs 19.0%, p<0.001), conversion to VA ECMO (14.5% vs 4.1%, p<0.001), and higher pump flows at 4 h from ECMO initiation (112.7 vs 105.5 mL/Kg/min, p<0.001), but lower at 24 h (100.3 vs 104.0 mL/Kg/min, p = 0.004), and a higher proportion of them experienced hemorrhagic (29.3% vs 18.3%, p<0.001), cardiovascular (60.8% vs 45.8%, p<0.001), and mechanical (42.5% vs 32.6%, p<0.001) complications compared to VVDL patients. After adjusting for propensity scores and the multi-level nature of ELSO data, there were no differences in neurologic outcomes, pump flows, or mortality. Rather, VVDL+V cannulation was associated with higher rates of conversion to VA ECMO (adjusted odds ratio [AOR] 43.3, 95% CI 24.3 – 77.4, p<0.001), and increased mechanical (AOR 2.2, 95% CI 1.6 – 3.0, p<0.001) and hemorrhagic (AOR 2.0, 95% CI 1.4 – 3.0, p<0.001) complications.ConclusionsIn this analysis, VVDL+V cannulation was not associated with any improvement in neurologic outcomes, pump flows, or mortality, but was rather associated with higher rates of conversion to Veno-Arterial ECMO, mechanical, and hemorrhagic complications.     

Comparing epidemiologic features,outcomes, and diagnostic and therapeutic procedures of traumatic patients before and during COVID-19 pandemic: Data from the National Trauma Registry of Iran

PurposeTo prepare for future possible communicable disease epidemics/pandemics, health care providers should know how the COVID-19 pandemic influenced injured patients. This study aimed to compare epidemiologic features, outcomes, and diagnostic and therapeutic procedures of trauma patients admitted to a university-affiliated hospital before and during the pandemic.MethodsThis retrospective study was performed on data from the National Trauma Registry of Iran. All injured patients admitted to the hospital from July 25, 2016 to March 10, 2021 were included in the study. The patients were excluded if they had hospital length of stay less than 24 h. The injury outcomes, trauma mechanisms, and therapeutic and diagnostic procedures of the 2 periods: before (from July 25, 2016 to February 18, 2020) and during (from February 19, 2020 to March 10, 2021) COVID-19 pandemic were compared. All analyses were performed using STATA version 14.0 software (Stata Corporation, College Station, TX).ResultsTotally, 5014 patients were included in the registry. Of them, 773 (15.4%) were registered after the beginning of the COVID-19 pandemic on February 19, 2020, while 4241 were registered before that. Gender, education level, and cause of injury were significantly different among the patients before and after the beginning of the pandemic (p < 0.001). In the ≤ 15 years and ≥ 65 years age groups, injuries decreased significantly during the COVID-19 pandemic (p < 0.001). The frequency of intensive care unit (ICU) admission decreased from 694 (16.4%) to 88 (11.4%) (p < 0.001). The mean length of stay at the hospital (days) and at the ICU (days) declined as follow: 8.3 (SD = 17.2) vs. 5.5 (SD = 6.1), p < 0.001 and 7.5 (SD = 11.5) vs. 4.5 (SD = 6.3), p < 0.022. The frequency of diagnostic and therapeutic procedures before and during the pandemic was as follows, respectively: ultrasonography 905 (21.3%) vs. 417 (53.9%) (p < 0.001), echocardiography 313 (7.4%) vs. 107 (13.8%) (p < 0.001), angiography 1597 (37.7%) vs. 534 (69.1%) (p < 0.001), MRI 166 (3.9%) vs. 51 (6.6%) (p < 0.001), surgery 3407 (80.3%) vs. 654 (84.6%) (p < 0.001), and internal/external fixation 1215 (28.6%) vs. 336 (43.5%) (p < 0.001).ConclusionThe pandemic affected the epidemiology of traumatic patients in terms of gender, age, educational level, and trauma mechanism. It changed the outcomes of injured patients: ICU admission, length of stay at the hospital and ICU decreased. The patients received more diagnostic and therapeutic procedures during the pandemic. To be more precise, more research is needed on the details.     

Uncomplicated gastroschisis care in the US and Kenya: Treatment at two tertiary care centers

BackgroundGastroschisis is a common birth defect with < 5% mortality in high income countries, but mortality in sub Saharan Africa remains high. We sought to compare gastroschisis management strategies and patient outcomes at tertiary pediatric referral centers in the United States and Kenya.MethodsThis retrospective chart review examined uncomplicated gastroschisis patients treated at Riley Hospital for Children in Indianapolis, USA (n = 110), and Shoe4Africa Children's Hospital in Eldoret, Kenya (n = 75), from 2010 to 2018. Analyzed were completed using Chi square, Fisher's exact, and independent samples t tests and medians tests at the 95% significance level.ResultsSurvival in the American cohort was double that of the Kenyan cohort (99.1% vs 45.3%, p< 0.001). Sterile bag use for bowel containment was lower in Kenya (81.3% vs 98.1%, p< 0.001), but silo use was comparable at both institutions (p = 0.811). Kenyan patients had earlier median enteral feeding initiation (4vs 10 days, p< 0.001) and accelerated achievement of full enteral feeding (10vs 23 days, p< 0.001), but none received TPN. Despite earlier feeding, Kenyan patients displayed a higher prevalence of wound infections (70.8% vs 17.1%, p< 0.001) and sepsis (43.9% vs 4.8%, p< 0.001). In Kenya, survivors and non survivors displayed no difference in sterile bag use, hemodynamic stability, all cause infection rates, or antibiotic free hospital days. Defect closure (p< 0.001) and enteral feeding initiation (p< 0.001) were most predictive of survival.ConclusionImproving immediate response strategies for gastroschisis in Kenya could improve survival and decrease infection rates. Care strategies in the US can center on earlier enteral feeding initiation to reduce time to full feeding.Level of evidence: Level III.