BACKGROUND:Pneumonia is a common lower respiratory tract infection (LRI) and the leading cause of pediatric hospitalization in the United States. Given its frequency, children with pneumonia may ...require surgery during their hospital course. This poses serious anesthetic and surgical challenges because preoperative pulmonary status is among the most important risk factors for postoperative complications. Although recent adult data indicated that preoperative pneumonia was associated with poor surgical outcomes, comparable data in children are lacking. Therefore, our objective was to investigate the association of preoperative pneumonia with postoperative mortality and morbidity in children.
METHODS:Using the National Surgical Quality Improvement Program database, we assembled a retrospective cohort of children (<18 years) who underwent inpatient surgery between 2012 and 2015. Our primary outcome was the time to all-cause 30-day postoperative mortality that we evaluated using Cox proportional hazards regression models. For the secondary outcomes, including 30-day postoperative morbidity events, we used Fine-Gray models to account for competing risk by mortality. We also evaluated the association of preoperative pneumonia with duration of postoperative mechanical ventilation and postoperative hospital length of stay. We used propensity score weighting methods to adjust for potential confounding factors, whose distributions differ across the pneumonia groups.
RESULTS:Among 153,242 children who underwent inpatient surgery, 0.7% (n = 867) had preoperative pneumonia. Compared with those without preoperative pneumonia, children with preoperative pneumonia had a higher risk of mortality throughout the 30-day postoperative period (hazard ratio HR, 4.10; 95% confidence intervals CI, 2.42–6.97; P < .001). Although not statistically significant, children with preoperative pneumonia were twice as likely to develop cardiovascular complications compared to children without preoperative pneumonia (HR, 2.10; 95% CI, 1.17–3.75; P = .012). Furthermore, children with preoperative pneumonia had longer duration of postoperative ventilation (incidence rate ratio, 1.47; 95% CI, 1.26–1.71; P < .001). Finally, children with preoperative pneumonia were estimated to be 56% less likely to be discharged within the 30 days following surgery, compared to children without preoperative pneumonia (HR, 0.44; 95% CI, 0.40–0.47; P < .001).
CONCLUSIONS:Preoperative pneumonia was strongly associated with increased incidence of postoperative mortality and complications in children. Clinicians should make concerted efforts to screen for preoperative pneumonia and consider whether proceeding with surgery is the most expedient course of action. Our findings may be helpful in preoperative discussions with parents of children with preoperative pneumonia for risk stratification and postoperative resource allocation purposes.
Varying results have been reported in the investigation of human leukocyte antigen (HLA) mismatching and bronchiolitis obliterans syndrome (BOS) after lung transplantation (LTx).
The UNOS database ...was queried for the period 1997 to 2013 to examine HLA mismatching and its association with BOS in LTx.
Of 16,959 first-time adult LTx recipients, 16,854 were included in the univariate Cox analysis and Kaplan-Meier survival function evaluation, and 14,578 were included in multivariate Cox models. Multivariate Cox analysis showed that the number of total HLA mismatches was significantly associated with greater hazard of BOS (HR = 1.060; 95% CI 1.013 to 1.108; p = 0.011), as was the presence of 2 HLA-A mismatches, when compared with 0 or 1 mismatch at that locus (HR = 1.128; 95% CI 1.026 to 1.240; p = 0.012). These results were confirmed using competing-risks regression models that adjusted for death before BOS diagnosis. Multivariate Cox models identified no significant association with BOS hazard for HLA-B (HR = 1.014; 95% CI 0.914 to 1.126; p = 0.785) or HLA-DR (HR = 1.085; 95% CI 0.987 to 1.193; p = 0.090) mismatches. Higher body mass index was associated with increased risk for BOS, whereas older age was protective against BOS. Induction with alemtuzumab (HR = 0.343; 95% CI 0.252 to 0.467; p < 0.001) or basiliximab (HR = 0.862; 95% CI 0.758 to 0.980; p = 0.023) and longer ischemic time (HR = 0.909; 95% CI 0.877 to 0.942; p < 0.001) were associated with lower hazard of BOS.
Total HLA mismatches are associated with increased risk for BOS, specifically at the A locus. Induction with alemtuzumab or basiliximab reduced the risk, whereas greater ischemic time appears to also be protective.
Background The influence of age and gender on survival after lung transplant in patients with idiopathic pulmonary fibrosis (IPF) is not well defined. Methods The United Network for Organ Sharing ...database was queried to identify IPF patients receiving lung transplant between 2005 and 2015. Results There were 6,677 patients receiving lung transplant between May 2015 and June 2015 who met the inclusion criteria, predominantly males (n = 4,769, 71%). Within 1 year posttransplant, the survival curves of male and female recipients diverged, with male recipients having significantly worse survival (log-rank test p = 0.008). Univariate Cox proportional hazards regressions demonstrated no gender difference in survival below age 65 years (HR = 1.051; 95% CI = 0.945, 1.168; p = 0.362) but a significant increase in mortality hazard associated with male gender among patients age 65 years and older (HR = 1.161; 95% CI = 1.000, 1.347; p = 0.049). Multivariable Cox regression accounting for age modulation of the gender effect further demonstrated the emergence of a male disadvantage in post-transplant survival above age 65 years at transplantation. Conclusions In patients with IPF receiving lung transplant at greater than 65 years of age, male gender is associated with significantly increased risk for death, so referral for lung transplant in IPF should be considered early in the disease course.
Acute pancreatitis (AP) occurs among patients with pancreas-sufficient cystic fibrosis (PS-CF) but is reportedly less common among patients with pancreas-insufficient cystic fibrosis (PI-CF). The ...incidence of AP may be influenced by cystic fibrosis transmembrane conductance regulator (CFTR) modulator use. We hypothesized that CFTR modulators would reduce AP hospitalizations, with the greatest benefit in PS-CF.
MarketScan (2012-2018) was queried for AP hospitalizations and CFTR modulator use among patients with CF. Multivariable Poisson models that enabled crossover between CFTR modulator treatment groups were used to analyze the rate of AP hospitalizations on and off therapy. Pancreas insufficiency was defined by the use of pancreas enzyme replacement therapy.
A total of 10,417 patients with CF were identified, including 1,795 who received a CFTR modulator. AP was more common in PS-CF than PI-CF (2.9% vs 0.9%, P = 0.007). Overall, the observed rate ratio of AP during CFTR modulator use was 0.33 (95% confidence interval CI 0.10, 1.11, P = 0.07) for PS-CF and 0.38 (95% CI 0.16, 0.89, P = 0.03) for PI-CF, indicating a 67% and 62% relative reduction in AP hospitalizations, respectively. In a subset analysis of 1,795 patients who all had some CFTR modulator use, the rate ratio of AP during CFTR modulator use was 0.36 (95% CI 0.13, 1.01, P = 0.05) for PS-CF and 0.53 (95% CI 0.18, 1.58, P = 0.26) for PI-CF.
CFTR modulator use is associated with a reduction in AP hospitalizations among patients with CF. These observational data support the prospective study of CFTR modulators to reduce AP hospitalizations among patients with CF.
•In the era of widely available highly effective modulator therapy, life expectancy for people with cystic fibrosis (PwCF) is expected to increase, and access to preventive care and age-appropriate ...screening is crucial in preserving longevity.•Using Truven Health Marketscan, we performed a retrospective analysis for commercially insured adult PwCF compared to adults without cystic fibrosis (CF). We discovered comparable-to-superior rate of preventive service utilization in PwCF relative to the general population, except for those between 18–27 years of age.•Our findings establish the important need of meeting the high primary care needs of PwCF, and call to attention the need to focus on care discontinuity within a vulnerable transitional-age adult population.•More than ever in CF history, it is important to integrate primary care physicians into the long-term care team for PwCF. This process should begin as early as during adolescence in order to ease the transition into adulthood.
As the life expectancy of the cystic fibrosis (CF) population is lengthening with modulator therapies, diligent age-appropriate screening and preventive care are increasingly vital for long-term health and wellbeing.
We performed a retrospective analysis comparing rates of receiving age- and sex-appropriate preventive services by commercially insured adult people with CF (PwCF) and adults without CF from the general population (GP) via the Truven Health MarketScan database (2012–2018).
We captured 25,369 adults with CF and 488,534 adults from the GP in the United States. Comparing these groups, we found that 43% versus 39% received an annual preventive visit, 28% versus 28% were screened for chlamydia, 38% versus 37% received pap smears every 3 years (21–29-year-old females), 33% versus 31% received pap smears every 5 years (30–64-year-old females), 55% versus 44% received mammograms, 23% versus 21% received colonoscopies, and 21% versus 20% received dyslipidemia screening (all screening rates expressed per 100 person-years). In age-stratified analysis, 18–27-year-old PwCF had a lower rate of annual preventive visits compared to adults in the same age group of the GP (27% versus 42%).
We discovered a comparable-to-superior rate of preventive service utilization in adults with CF relative to the GP, except in young adulthood from 18–27 years. Our findings establish the importance of meeting the primary care needs of adults with CF and call for development of strategies to improve preventive service delivery to young adults.
Objectives:
To determine whether gut permeability is associated with post‐discharge growth and systemic inflammation among hospitalized children in low‐ and middle‐income countries.
Methods:
Children ...aged 2–23 months being discharged from Civil Hospital Karachi (Pakistan) and Migori County Referral Hospital (Kenya) underwent lactulose‐rhamnose ratio (LRR) permeability testing and were compared to age‐matched children from their home communities. Linear mixed effect models estimated the associations between LRR among discharged children with change in length‐for‐age (LAZ) and weight‐for‐age z score (WAZ) at 45, 90, and 180 days after discharge. Linear regression tested if relationships between LRR, systemic inflammation C‐reative protein (CRP), Cluster of Differentiation 14 (CD14), Tumour Necrosis Factor Alpha (TNFα), Interleukin‐6 (IL‐6), and enterocyte damage Intestinal Fatty‐Acid Binding protein (I‐FABP) differed between the hospitalized and community groups.
Results:
One hundred thirty‐seven hospitalized and 84 community participants were included. The hospitalized group had higher log‐LRR 0.43, 95% confidence interval (CI): 0.15–0.71, P = 0.003 than the community children. Adjustment for weight‐for‐length z score at discharge attenuated this association (0.31, 95% CI: 0.00–0.62, P = 0.049). LRR was not associated with changes in WAZ or LAZ in the post‐discharge period. Associations between LRR and CRP (interaction P = 0.036), TNFα (P = 0.017), CD14 (P = 0.078), and IL‐6 (P = 0.243) differed between community and hospitalized groups. LRR was associated with TNFα (P = 0.004) and approached significance with CD14 (P = 0.078) and IL‐6 (P = 0.062) in community children, but there was no evidence of these associations among hospitalized children.
Conclusions:
Although increased enteric permeability is more prevalent among children being discharged from hospital compared to children in the community, it does not appear to be an important determinant of systemic inflammation or post‐discharge growth among hospitalized children.
Despite advances in treatment for cystic fibrosis (CF), liver disease remains a major contributor to morbidity and mortality for persons with CF. Therefore, liver transplantation may be considered in ...end-stage CF-related liver disease. We present a young patient with CF who underwent solo liver transplantation and has successfully restarted on elexacaftor/tezacaftor/ivacaftor without significant pulmonary or hepatic complications after transplant.
Pseudomonas aeruginosa is a ubiquitous environmental organism and an opportunistic pathogen that causes chronic lung infections in the airways of cystic fibrosis (CF) patients as well as other ...immune-compromised individuals. During infection, P. aeruginosa enters the terminal bronchioles and alveoli and comes into contact with alveolar lining fluid (ALF), which contains homeostatic and antimicrobial hydrolytic activities, termed hydrolases. These hydrolases comprise an array of lipases, glycosidases, and proteases and thus, they have the potential to modify lipids, carbohydrates and proteins on the surface of invading microbes. Here we show that hydrolase levels between human ALF from healthy and CF patients differ. CF-ALF influences the P. aeruginosa cell wall by reducing the content of one of its major polysaccharides, Psl. This CF-ALF induced Psl reduction does not alter initial bacterial attachment to surfaces but reduces biofilm formation. Importantly, exposure of P. aeruginosa to CF-ALF drives the activation of neutrophils and triggers their oxidative response; thus, defining human CF-ALF as a new innate defense mechanism to control P. aeruginosa infection, but at the same time potentially adding to the chronic inflammatory state of the lung in CF patients.
Background The effect of lung transplantation (LTx) in patients afflicted with cystic fibrosis (CF) and pulmonary hypertension (PH) at placement on the waiting list is not well studied. Methods To ...predict the relationship between initial mean pulmonary artery pressure (MPAP) and hazard ratio (HR) of death after listing associated with LTx in adult patients with CF, the United Network for Organ Sharing database was queried for the years 2005 to 2013. Survival was assessed from waiting list entry until death on the waiting list, death after LTx, or censoring. A multivariate Cox model was performed to estimate the HR of LTx conditional on MPAP at listing. Results Of 1,841 patients with CF, 10% (177) died on the waiting list, 18% (325) were censored without undergoing LTx, and 73% (1,339) underwent transplantation, 361 of whom died after transplantation. A multivariate Cox model of survival since list entry including 1,336 patients found a protective but statistically insignificant benefit of LTx for patients whose MPAP at listing was 25 mm Hg (HR, 0.879; 95% confidence interval CI, 0.657–1.177; p = 0.388), yet LTx was predicted to be more protective at higher initial MPAP levels, as indicated by the significant interaction term between LTx and MPAP (HR, 0.953; 95% CI, 0.928–0.978; p < 0.001). The predicted LTx HR and 95% CI were protective (HR < 1) at p < 0.05 for patients with MPAP greater than or equal to 30 mm Hg at listing. Conclusions Survival benefit of LTx in CF was increasingly protective at higher MPAP levels, with a severity level of PH established above which a survival advantage of LTx was found.
•A review to describe exocrine pancreas function during CFTR modulator treatment.•CFTR modulator treatment reduces acute pancreatitis by 85% overall.•Treatment converts pancreas insufficiency to ...sufficiency in 20–50% of subjects.•Treatment reduces pancreatic inflammation assessed by amylase, lipase, and trypsin.
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve pulmonary outcomes in subjects with cystic fibrosis (CF); however, the effects on pancreatic manifestations are not well characterized. We hypothesized that CFTR modulators would improve measures of exocrine pancreatic function and outcomes.
We performed a systematic search to identify studies reporting measures of the exocrine pancreas in humans treated with CFTR modulators. Only studies reporting baseline and on-treatment assessments were included.
Of 630 identified studies, 41 met inclusion criteria. CFTR modulators reduced acute pancreatitis events by 85% overall (rate ratio 0.15, 95% confidence interval (CI) 0.04, 0.52), with a greater effect seen in the subgroup with pancreas sufficient CF (PS-CF) (rate ratio 0.13 (95% CI 0.03, 0.53). Among 293 subjects with baseline and on-treatment evaluation of pancreas sufficiency, 253 were pancreas insufficient at baseline and 54 (21.3%) converted to pancreas sufficiency. Of 32 subjects with baseline FE-1 values <200 mcg/g, 16 (50%) increased to ≥200 mcg/g. Serum trypsin decreased by a mean of 565.9 ng/mL (standard deviation (SD) 311.8), amylase decreased by 38.2 U/L (SD 57.6), and lipase decreased by 232.3 U/L (SD 247.7).
CFTR modulator use reduces acute pancreatitis frequency and improves indirect measures of exocrine pancreas function. Future interventional studies that evaluate the mechanism and impact of CFTR modulators on acute pancreatitis and pancreas sufficiency in patients with CFTR dysfunction are warranted.
PDF
